Plasma cell discrepancies exist on this continuum. Usually the big cutoff is between this smoldering myeloma and multiple myeloma. And your MGUS is classically less than 3 g/dL and less than 10% in the marrow with no end-organ damage. Your smoldering elevates to when people have greater than 10% in the marrow or greater than 3 g/dL and a bone marrow plasma cell percentage of 10-60%. Typically in your typical bone marrow biopsy, you will see about 1-3% plasma cells.

Again, the delineation between MGUS and smoldering myeloma, which are by definition asymptomatic conditions, is usually this presence of this CRAB criteria. One is four criteria that we are pretty familiar with between this calcium elevation, renal failure, anemia or bone disease.

What is more recent is this addition of the SLiM criteria, which has these additional criteria, which would meet criteria for multiple myeloma and proceed with treatment. Treatment in one of these other three criteria: including a bone marrow percentage of greater than 60%; light chain ratio of greater than 100 to one; or MRI studies with greater than one focal lesion, that is greater than 5 mm size.

These patients used to be grouped as smoldering myeloma patients, but essentially what we have seen in these patients have such a high risk of progression of over about 80% over the course of two years that we treat them aggressively as a full-blown diagnosis of multiple myeloma in anticipation that we are trying to prevent organ failure and preventing one of those CRAB criteria from ever kind of showing.

Next slide, please.

[00:07:36]

Updated Progression of Multiple Myeloma

Again, this is the kind of classic slide that we see for multiple myeloma.

Again, we think of myeloma as an incurable disease, although that kind of paradigm is potentially changing with the advent of CAR T in combination with autologous stem cell transplant and bispecifics as well, too.

Typically, people present with the highest disease burden when they first get diagnosed and have a lot of those end-organ damage features. Along the line, we do expect people to relapse. There are a small portion of patients that I have seen that have been long-term responders after transplant, like about 3-5% that tend to be a kind of long-term, almost cure. You are seeing that people with CAR T and other types of cellular therapies that are maybe long-term responders and seeing their response plateau. But again, we do expect patients to run through multiple lines of therapy, but with the advent of new types of cellular therapy and bispecifics, we are seeing people stay in remission for longer periods of time and having longer life expectancies.

So certainly, myeloma used to be very much a very life-limiting disease, but now we are seeing patients live decades with the disease. And then, with how things are changing in terms of the treatment landscape, we are having better and better outcomes and having people live longer and better quality of life.

Next slide, please.

[00:08:55]

Selecting Regimens for ASCT-Eligible Patients

All right. Selected regimens for autologous stem cell transplant-eligible patients.

Next slide, please.

[00:09:04]

Patient Case: Newly Diagnosed MM

We will start with the patient case. Again, this is a pretty typical case. 58-year-old woman with no significant past medical history. She is found to be anemic.

Initial labs, so hemoglobin 9.8, so meeting that CRAB criteria of kind of less than 10 or less than 2.0 g per baseline. Albumin 3.3, total protein of 9, serum creatinine 0.8, calcium 8.5, no evidence of folate, B12, iron deficiency. SIFE/SPEP shows an IgG kappa monoclonal protein of 3.5. Again, you see your elevated IgG, kappa is 50, lambda is 4.5 with a ratio of 11. LDH is normal at 150, beta-2 microglobulins is slightly high at 3.6. The PET/CT shows multiple hypermetabolic areas in the bone with those classic myeloma lytic-type lesions. Bone marrow shows 65% atypical plasma cells. And FISH shows gain of 1q, trisomy 9, and trisomy 11.

Next slide.

[00:09:58]

Poll 2: In your current practice, what induction therapy would you recommend for this patient?

All right, we will have another question here. In your current practice, what induction therapy would you recommend for this patient?

1. Bortezomib, lenalidomide, dexamethasone, your classic RVd.
2. Carfilzomib, Len, Dex, so KRd;
3. Dara, bortezomib, Len, Dex, so Dara-RVd; or
4. Cyclophosphamide, bortezomib, Dex, or CyBorD; or
5. Try something else.

You can open up.

Speaker: Polling is open.

Dr. McKay: All right. So we have got kind of a smattering of different regimens. It seems like the two people who are most in favor was B and C, so KRd and Dara-RVd.

All right. We will go to the next slide.

[00:10:58]

Poll 3: Please take a moment to text in any challenges or barriers that you have encountered in your clinical practice addressing the care of patients with newly diagnosed multiple myeloma.

And if people want to take a second to scan this and see if there is any kind of feedback on barriers you have with your clinical practice addressing the care of patients with nearly diagnosable myeloma.

If people scan, I guess they can kind of respond to that throughout the presentation, right?

Speaker: Probably.

Dr. McKay: Okay. Okay, so let me know when we should move on.

Speaker: Everyone good?

Speaker: Yes.

[00:11:36]

Revised International Staging System (R-ISS)

Dr. McKay: Okay. So this is how we prognosticate myeloma. Again, the definition of what we consider the staging of myeloma and what is considered high-risk for myeloma has changed over time as we learn more about the disease.

And you can kind of see our first staging system, the ISS staging system, just really incorporated lab work, like your albumin, your beta-2. And you can kind of see as the staging systems have progressed, like R-ISS, which is the next kind of iteration of it, you can start incorporating things like our FISH, like your translocation(4;14), t(14;16), and deletion 17. It is just more genetic components to the disease instead of just straight markers.

And more recently, we had the R2-ISS. ISS includes a lot of the similar type of things with your LDH and then your beta-2 and your albumin, as well as incorporating 17p and t(4;14). And then you can see the kind of newer player in the game is this 1q, which has become more and more studied throughout all these new studies for myeloma.

You can go to the next slide.

[00:12:54]

Defining High Risk

This is another iteration of a kind of prognostication for myeloma determining risk score evaluation. And again, you can see that we keep incorporating more and more genetic factors into scoring and prognosticating myeloma.

So in this, they have t(4;14), t(14;16), t(14;20), del(17p). And again, that chromosome 17 is where P53 resides. So it tends to be kind of a poor prognostic factor across a range of malignancies. And then that gain amplification of 1q and 1p. On the chromosome 14 is where the heavy chain locus resides. That is why we see a lot of our higher-risk prognostication on that chromosome.

You can see there is some lab factors as well, too. Again, like we determine albumin and beta-2 microglobulin, which tends to be elevated in patients with renal failure. So people with already evidence of end-organ function, like in their present with renal disorder and sometimes even dialysis tend to have worse prognosis long-term.

And then there is clinical characteristics that make people higher-risk. First was plasma cell leukemia. The definition of plasma cell leukemia used to be greater than 20% circulating plasma cells. What we found is we have done more studies that basically any form of circulating plasma cells is a poor prognostic factor. We have even seen people with MGUS and smoldering myeloma in patients with circulating plasma cells, and those conditions are more likely to progress to myeloma.

And then the other thing that has been a hot kind of bed for studying as well, too, is what we call extramedullary involvement. Again, it was where people have disease outside, they are not outside the bones or seeing the liver, lungs, things like that, which are not typical sites of myeloma. Those patients tend to have lower response to therapy and lower duration of response as well, too.

And then we have clinical, we call it functional high-risk, where people either are refractory to their primary induction regimen, so your quad or triplet, or if people have progression from their initial induction therapy within the first 18 months, those patients tend to have shorter remissions and tend to have a more aggressive disease phenotype.

Next slide.

[00:15:02]

Updated IMS/IMWG Consensus Recommendations for Defining High-Risk Multiple Myeloma

And this is the most updated high-risk consensus that came out last year from IMWG. You can see it incorporates a lot of things that we have already talked about.

Again, high beta-2 microglobulin. And again, you can see a lot of these genetic kind of factors as well, too. A little bit different in terms of, you can see deletion 17p is still there, but they have added something different in terms of a mutation of TP53, which has not been recognized on previous prognostic scoring systems, as well as you can see that what considers high-risk for some of these FISH abnormalities, including gain 1q, has to be in conjunction with other translocations, including t(4;14), t(14;16), or t(14;20). So you can see the presence of kind of these chromosome 1 abnormalities has become very prominent in terms of our risk factors scoring for multiple myeloma.

Next slide.

[00:16:00]

Induction and Maintenance Principles for Newly Diagnosed Transplant-Eligible Multiple Myeloma

Again, with myeloma being an incurable disease, our overall goal for most of our regimens is to maximize depth and duration of first response while maintaining quality of life. Again, I always tell patients when they get diagnosed with myeloma, this is a marathon, so we do not want to kind of blow your engine out in the first mile here.

So we want to keep people out of a long, fruitful, high quality-of-life, and we are able to do that with a majority of our patients, I think, these days. The standard of care, I think, has shifted to the quad era, where we are using a four-drug regimen, which we kind of take one drug from each of our primary drug classes, like your CD38, your IMiDs with lenalidomide, your proteasome inhibitors with usually Velcade or carfilzomib, and then dexamethasone as well, too, followed by consolidation with autologous stem cell transplant.

And as of right now, the FDA-approved maintenance regimen is lenalidomide, although the role of maintenance is changing in terms of especially patients with a high-risk phenotype, as we discussed earlier.

Next slide.

[00:17:06]

Randomized Trials on Quad Induction + ASCT

All right. So, again, the standard of care for myeloma induction has changed over time.

Velcade was kind of the first cover that really changed the game. We were using doublets, and then lenalidomide came along, and that was added to that, and we got your bortezomib, lenalidomide, dexamethasone triplet. And now I think we are kind of firmly in the area of quads. So we are building on top of that platform with triplets and then adding the daratumumab, your anti-CD38, to the induction.

So, again, you have four drugs, with one from each kind of your drug classes, as well as dexamethasone. And for vascular patients, that has been the building block for their induction therapy.

There have been studies. We will go through a few of these studies in the next couple of slides as well, too.

Advance to the next slide, please.

[00:17:58]

GRIFFIN: Phase II Trial of Dara +VRd vs VRd for Transplant-Eligible Patients with NDMM

The first and a real game-changing study that ushered us into the quad era was the GRIFFIN study.

We were participating in a study, led by one of our counterparts down in Charlotte, Pete Voorhees. Again, you can see this was a comparison between lenalidomide, the R, the bortezomib, the V, the dexamethasone D. Where is that compared to a quad-based therapy?

So you get all those three drugs plus the daratumumab. You can see very parallel in terms of treatment plans, comparing this quad-based therapy with autologous stem cell transplant consolidation. And then in the maintenance, they got two cycles of consolidation with either the quad or the RVd based off what they are randomized to.

And then the maintenance was either a single agent with lenalidomide or a doublet with daratumumab and lenalidomide. The primary endpoint was the stringent CR by the end of consolidation. So they went at the end of that cycle six. And with, again, key second endpoints being MRD negativity, response rate, VGPR, and then overall survival as well too. This is for patients with transplant-eligible myeloma. As you can see, they got a transplant during this kind of protocol.

Next slide.

[00:19:12]

GRIFFIN: Response Rates

And again, what we are seeing between these two groups here, we have the quad on the left, and you have the triplet on the right. You can see higher response rates and deeper responses in patients that got the quad.

You can see in the final analysis, patients with the CR or better were 83%, and the quad-based group versus 60% in the triplet-based group. You can see those responses tended to deepen over time. So even in patients that were high after consolidation and after maintenance, sometimes we will see people deepen in their responses as well, too.

Go to the next slide.

[00:19:50]

GRIFFIN: PFS and OS

I think this is one of the key slides. Again, although it was not powered for PFS or overall survival, you can see this curve start really kind of branching out, that kind of 30-month mark where you can start seeing the PFS difference between 87% and 70%.

One of the controversial things that people were hesitant in adopting quads was the part on the right here where you can see that although people had a better progression-free survival, we were not really seeing overall survival benefits. We think that is probably for a few different reasons. First is just that we have so many much better salvage regimens at this point with CAR T, bispecifics, and things like that as well, too.

But there are more studies coming down the line that will have long-term overall survival benefit, as well.

But you can go to the next slide.

[00:20:40]

PERSEUS: Phase III Trial of Dara +VRd vs VRd for Transplant-Eligible Patients with NDMM

Again, this came out kind of piggybacked off the GRIFFIN study, and this was the Phase III confirmatory trial, the PERSEUS trial.

And you can see, very similar trial design. Again, it is your quad versus triplet with autologous stem cell transplant, two cycles of consolidation, and then randomized domains with DR versus Len by itself. And there was a second randomization you can see on the top-right there for people based off their MRD stratification.

But the difference between this, the GRIFFIN and the PERSEUS trial, you can see that primary endpoint was PFS, again, progression-free survival, versus MRD at the end of consolidation. So, again, these patients had longer-term follow-up. This was a bigger study, enrolled more patients, and it was higher power to really figure out these more kind of nuanced endpoints.

Next slide.

[00:21:36]

PERSEUS: PFS and MRD Negativity Rate

Again, a bigger trial, but, again, you can really start to appreciate this progression-free survival. Again, difference of about 17% at about four years of follow-up.

And, again, the key point is people are having longer responses and also deeper responses. So, you can see even at key MRD thresholds, like MRD 10^-5 and MRD 10^-6, you can see the quad outcompeted the triplet. And then the other thing that we are going to see, and we will kind of touch on a little bit more later, is not just deep responses, but sustained deeper responses.

You can see on the right-hand bar graph, people are having deep responses, but responses that were maintained over the course of a year for greater than 12 months.

Go to the next slide.

[00:22:25]

PERSEUS MRD Analysis: MRD Negativity in Subgroup With High-Risk MM

Again, one of the key areas of research that has been a hot topic in myeloma is these high-risk groups.

We know that classically, for a lot of our standard-risk patients, they tend to do well long-term. It is these high-risk patients that we know we have a hard time getting deep responses, and maintaining their responses. While a lot of these standard-risk patients tend to do well with triplet or quads, it is really these high-risk patients that we are really trying to rescue and trying to figure out, is there any treatment strategy we can to optimize their treatment and make sure they try to equalize their genetic determinants that make them a poor prognostic long term.

But you can see for patients that got quad-based therapy, the MRD negativity, their depth of response was much deeper, as well as their sustained MRD negativity and their depth of response. PFS was much better as well, too. We are seeing that there is a sustained and deeper benefit for patients that are exposed to quad-based therapy in their induction therapy.

Go to the next slide.

[00:23:34]

Timing of ASCT

All right. So, we talked about timing-autologous stem cell transplant.

Next slide.

[00:23:42]

DETERMINATION: PFS (Primary Endpoint)

This is the key data that I quote a lot of my patients when they come to talk about stem cell transplant. This is a determination study.

This is basically a triplet-based regimen, so Len, bortezomib-Dex with transplant versus deferred transplant or no transplant with just the triplet. And you can see here the primary endpoint was PFS.

You can see a fairly separated curve there. So, PFS difference of 67 months versus 46 months. Again, when I quote patients, I am like, a transplant will probably give you a little less than two years of sustained remission.

Go to the next slide.

[00:24:28]

DETERMINATION: PFS by Cytogenetic Risk

But what I really think transplant still has a great amount of utility in my own patients is on the left here. So, people with high-risk cytogenetics. So, these are people that have t(4;14), t(14;16), or deletion 17p.

You can see the PFS difference is much more pronounced. So, instead of like 46 versus 67 months, you can see for high-risk patients, across the board, they tend to do worse and have less, lower PFS. But you can see the PFS difference is 17 months versus 55 months.

I tell my patients, if you are high-risk, your transplant, on average, will buy you about three times as long in remission. Again, there is a little bit of a selection bias from people that are able to kind of complete the protocol. But, again, transplant, I think it definitely has more of a demonstrated benefit in patients with higher-risk phenotype.

For standard-risk, you can see that the curves still separate, but it is not quite as dramatic as with high-risk. So, there still is a benefit to transplant. And I do offer it to all my patients, but I definitely emphasize a little bit more for our high-risk patients.

Next slide.

[00:25:38]

FORTE: Phase II Trial of KRd ± ASCT Followed by KR or R Maintenance in NDMM

This is the FORTE trial. Again, this was reported out a few years ago at this point.

But, again, a three-arm trial, trying to compare transplant, as well as different induction regimens. So, these patients either got Cytoxan, carfilzomib, or Dex, or KCd, or KRd. So, Carfi, lenalidomide, Dex.

Those patients were, both got transplant, or there is a single arm by itself, too, that basically just got Carfi, lenalidomide, Dex, continuously. So, comparing different induction regimens, and then comparing transplant, as well, too. And there was a second randomization on the backside, as well, too, with a single agent of maintenance with lenalidomide versus a doublet with carfilzomib and lenalidomide.

And, again, primary endpoint was VGPR, post-induction PFS, as well as the secondary endpoints, overall survival. So, pretty typical trial design for this.

Go to the next slide.

[00:26:35]

FORTE: PFS

Again, you can see that between the separation of the curves. The first two curves there, the green and the blue, again, these are patients that got carfilzomib-based induction therapy. You see a little bit of separation of the curves of patients that got carfilzomib plus transplant.

I think the more key thing here is the second part of the graph, or the second graph here, where you can see a clear separation of the curve for patients that got a doublet maintenance versus a single. So, again, improved PFS for patients that get two drugs for maintenance versus a single.

Go to the next slide.

[00:27:18]

Maintenance

Maintenance. I think this is where we will talk a little more.

[00:27:22]

Lenalidomide Maintenance After ASCT in NDMM

Again, the paradigm for maintenance for a long period of time has been lenalidomide.

There were some trials that, when the advent of lenalidomide maintenance came out, that showed overall survival benefit, and some that did not. Some that showed PFS benefit, some that did not. So, this is one of the seminal papers that kind of determined the role of lenalidomide maintenance. This is a McCarthy meta-analysis that was published back in 2017.

You can see the overall survival curve. You can see a separation of the curves there. So, there is an overall survival benefit for patients with Len maintenance, if you take the general population.

However, if you look at the forest plot here, I think the important thing is to look at, if you look at the patients with RI-SS stage III disease, you can see that it crosses the midline there, maybe even is over on the right-hand side of the hazard ratio of 1. Basically, the conclusion was that we know Len maintenance has overall survival benefit for a lot of our standard-risk patients, but it is kind of uncertain, or it is not enough for a lot of our high-risk patients. So, the question still remains in a lot of myeloma physicians' minds, what is the optimal maintenance for patients with high-risk myeloma? And that is kind of an area of ongoing study as well, too.

Usually, a lot of our maintenance platforms are based off of Len. For our high-risk patients, it usually ends up being Len plus something else, just because we know that probably single-agent Len is probably not sufficient maintenance for our high-risk patients.

Go to the next slide.

[00:28:56]

Phase III Myeloma XI Trial: PFS With Len Maintenance in ASCT-Eligible Patients by Cytogenetic Risk

And this is the myeloma XI trial. It was a randomized trial that compared Len maintenance versus observation after stem cell transplant.

It is stratified based off of different risk categories. And then you can see that in terms of patients with standard-risk myeloma, you can see a pretty clear separation of the curves on the left. And then patients with high-risk and, again, ultrahigh-risk, you can kind of see those curves starting to shrink together a little bit, and especially with that high-risk patient.

It just shows that patients that do get Len maintenance after and with high-risk features, especially these double hits that have t(4;14), like a combination of these two different risk factors, they tend to do poorly. Len maintenance does not tend to kind of abrogate that risk. We are kind of showing that where there is a deficiency for these patients, and we need to kind of build on this and try to find different ways to really kind of optimize the maintenance regimens.

Go to the next slide.

[00:30:00]

Phase II FORTE: PFS With KR vs R Maintenance in NDMM According to Risk Status

Again, these are the PFS curves, and it just highlights, again, this is with the REV versus lenalidomide versus carfilzomib plus lenalidomide, and patients that have gotten those three different induction therapies. Again, you can see the progression-free survival benefit is improved across the board with an addition of a second agent, which is somewhat unsurprising.

Again, you add a second agent to someone's treatment, you would expect to get the regimen to last longer. But you can see the separation of curves, pretty separate in the standard-risk curves. But you can start to see that maybe in the high-risk or double-hit, that you might start seeing that the addition of a second agent might provide further benefit for these patients and maybe abrogate that risk a little bit.

All right, next slide.

[00:30:58]

ATLAS: Phase III Trial of KRD vs Lenalidomide as Posttransplant Maintenance Therapy in NDMM

All right, this is the ATLAS study. Again, this is another maintenance Phase III randomized study, KRd, so carfilzomib, lenalidomide, Dex versus lenalidomide as post-transplant maintenance and newly diagnosed multiple myeloma.

It was an international study. Again, patients had to complete induction and then have at least stable disease after autologous stem cell transplant and start their therapy within 120 days after transplant. Being randomized to one of these two regimens, they either got lenalidomide by itself or they got lenalidomide in combination with carfilzomib and dexamethasone.

If they were MRD-negative or high-risk, they stayed on that. If they did respond well and they were converted to MRD-negative, they could be deescalated to lenalidomide maintenance alone after eight cycles. Again, the primary endpoint was progression-free survival, with key endpoints being overall survival, MRD status, and safety.

But you can see for patients that got the triplet, their progression-free survival was significantly longer, 72 months versus 37 months. Their overall survival was higher as well too, so not reached in the triplet group versus 82 months in the lenalidomide-alone group.

Go to the next slide.

[00:32:38]

CASSIOPEIA Part 2: Daratumumab vs Observation

This is a CASSIOPEIA trial. This is an older induction, a Phase III trial for patients with multiple myeloma. So these patients, instead of using lenalidomide, used thalidomide for their induction therapy. So that is the T in the induction and kind of the acronyms there.

There were two randomizations. They either got VTd or Dara-VTd in induction, and then they were randomized to either observation or Dara in the second randomization. But the key point to this is that on the left-hand side there, you can see the patients that got a CD38 or Dara-based regimen and maintenance had an improved progression-free survival versus observation.

In the right curve, you can see that the three top curves, the yellow, the purple, and the green, were all patients that got daratumumab at some point during their therapy, so either in induction or maintenance. You can see there is a big separation in the curve versus patients that got the Velcade, thalidomide, and dexamethasone in that gray curve, in the bottom, demonstrating the importance of daratumumab being at some point in patients' induction and maintenance.

So you can see, again, a clear separation of curves. The top curve is the patients that got the fullest Dara exposure, where they got in induction and maintenance. Again, comparing that to the gray curve, were patients that got just straight Velcade, thalidomide, Dex, and did not get any maintenance at all, you can see a clear benefit. But across the board, you can see that daratumumab does have a significant benefit for patients in their kind of induction and maintenance course for myeloma.

Next slide.

[00:34:31]

GRIFFIN: MRD Negativity Over Time

GRIFFIN, just to highlight the benefit of daratumumab in the induction and the MRD responses. So you can see even 10^-5 and 10^-6, 10^-6 being kind of our deepest MRD that we are assessing for now. You will see that adding daratumumab deepens responses. So you have, at the final analysis, you had 64% of patients that were MRD-negative at least 10^-5, versus only 30% of patients with a triple-based regimen. Again, we are seeing patients that are having very deep responses and also prolonged responses. And we know that patients that are in MRD negativity after induction tend to have the best prognosis overall, tend to have better survival and progression-free survival as well.

Next slide.

[00:35:21]

PERSEUS: PFS by Sustained MRD Negativity ≥ CR Status

Again, this is from the PERSEUS study. Again, this is the Dara-RVd versus RVd study. And what they are really trying to demonstrate here is that these plot-based regimens are not just giving people deep responses, but they are also keeping sustained deep responses.

One of the things that has been an issue with myeloma is that myeloma is a patchy disease. So there is probably some element of sampling variability whenever we are doing all this testing. So it is always nice to have sustained data points where you are seeing continuous MRD negativity.

And you can see the top curve. You do see that, again, the patients that are in MRD negativity for long periods of time. So in the top curve are people that have MRD-negative across a 12‑month period. They tend to do very well.

For us, where they get a triplet or a quad-based induction therapy. And you can see across the bottom curve that the people that are in even longer responses tend to have an even better progression-free survival. So we know that MRD negativity is a very good prognostic sign for patients for staying in remission for long periods of time.

And in conjunction with that, we know that people that get quad-based therapy and induction therapy are more likely to get into MRD negativity, and have sustained MRD negativity. A lot of our trials and our endpoints have moved towards moving towards MRD negativity as an endpoint. Because we know how well people do when they get MRD negativity, it is also an endpoint that we can capture early in their disease course. And we can get an idea of how well these regimens are working for people long term. So again, a lot of our regimens right now are aimed at trying to get people these deep 10^-6 MRD responses and also maintain them over long periods of time.

Next slide, please.

[00:37:13]

AURIGA: Daratumumab/Lenalidomide vs Lenalidomide as Posttransplant Maintenance Therapy for NDMM

This is the AURIGA trial. So this was comparing two different maintenance strategies. One was lenalidomide by itself, and this versus Dara and Len. The caveat to this is that patients were not Dara-exposed in the front line. And they had to have some sort of medical disease, so at least MRD positivity after stem cell transplant.

So it has some complications with applicability, because I think a fair amount of our patients are getting CD38-exposed in the front line now, so they would not have qualified for the study. But the endpoint, I think, is very interesting, where there is conversion of MRD negativity at the end of 12 months of treatment.

You can go to the next slide.

[00:38:00]

AURIGA: MRD Negativity at 12 Mo and PFS

You can see that the rates of MRD negativity conversion after 12 months were significantly higher with the addition of daratumumab to lenalidomide, 50% versus 18%. And you can see that the progression-free survival is also significantly improved with the addition of daratumumab in the maintenance for people that are MRD-positive. So this is where, again, for a lot of my patients who end up with MRD-positive, even if they are staying at risk, I end up keeping them on a doublet, because I know that there is a good chance that keeping them on some sort of doublet maintenance will convert them to MRD negativity and get them a better shot at staying in remission within their maintenance areas as long as possible.

Go to the next slide.

[00:38:44]

Treatment Considerations for ASCT-Ineligible Patients

All right, treatment considerations for transplant-ineligible patients.

All right, go next.

[00:38:50]

Defining High-Risk MM and Additional Considerations

Okay, I think we have touched on a lot of these before, too, again. It is defined as high-risk phenotype, which, again, is a dynamic and a little bit of an ever-changing kind of goal about what is high-risk in multiple myeloma.

Again, the things we talked about, some of the FISH testing for t(4:14), t(14;16), chromosome 1 abnormalities, del(17p) or TP53, as well as some lab-based abnormalities like elevated beta-2 microglobulin with a normal creatinine. Again, there are clinical features, including circulating plasma cells, extramedullary disease, again, disease outside the bone marrow, as well as some clinical characteristics, like people that are primary refractory to quad-based induction or rapid progression, so people that are progressing within 18 months of their initial therapy.

Go to the next slide.

[00:39:44]

The Evolution of Myeloma Therapy

Just as evolution of multiple myeloma therapy, again, it has been a very dynamic time for myeloma, and I think it has been very good for our patients. Again, now I think we are firmly in the quad area of multiple myeloma. I would say the standard care for our patients now is a quad-based therapy.

Again, you are getting your daratumumab plus lenalidomide plus Velcade or bortezomib plus dexamethasone for a majority of our patients. Sometimes different people like to substitute carfilzomib for patients with high-risk characteristics. And then consolidation with stem cell transplant is still, I think, standard care, although it has totally fallen out of favor.

And then new studies are there to evaluate the role of consolidations with other strategies like CAR T or bispecific, or even do patients need consolidation since our induction therapies are getting so good? Can we use MRD-adapted design to just keep people on their induction therapy or just transition to maintenance? Do we even need to go through these kind of more highly toxic barriers, like going through transplant? Can our portion just kind of be excluded from treatment?

Again, we talked about maintenance as well, too. Again, lenalidomide is kind of the basis of it. And then a lot of times a lot of our trials now are, can we add things to it? Do we add Dara? Do we add bispecifics? Can we do time-limited-based maintenance based off of MRD negativity. And then our alternate strategies with CELMoDs or other things are coming down the pipeline as well, too.

In rescue, this is kind of where myeloma is really taking off. We have a lot of different things that are available at our fingertips. Oftentimes, I think that for myeloma, the NCCN guidelines tend to be some of the least useful versus other disease phenotypes. We have a lot of different options, and I think oftentimes it is pretty confusing trying to figure out how to navigate it, which I think is a testament to how much myeloma has changed and how much we have available to our patients.

But again, with the quad-based area, I think we are also firmly in the cellular and bispecific area as well, too. I think the majority of our patients in the future will be exposed to CAR T or bispecific at some point in their course of therapy, as well as new different types of therapies like our CELMoDs or different small molecules like venetoclax, next-generation BCL-2 inhibitors, or even new bispecific targets or trispecific antibodies or armored CARs, all things that are kind of coming down the pipeline that I think will be game-changing for our patients.

Go to the next slide, please.

[00:42:32]

Factors Driving Treatment Decisions in MM

So factors that drive treatment decisions, again, I think risk stratification has been a big one, although it does not necessarily change a lot with the induction therapy, maybe substituting like bortezomib for carfilzomib. We know that long-term, the consolidation strategies may be different for these patients. I think what is becoming more and more research is our frailty for patients with myeloma.

Myeloma can be a very debilitating disease, but we also do not want the treatment to be worse than the disease as well, too. Are there ways that we can kind of balance treatment and the side effects and keeping the dose density up versus side effects and the response as well, too.

And also depth of response. As you demonstrate across the rest of the slides, we know that adding drugs tends to increase the depth and duration of response, but at what cost to the patient in terms of side effects. You know, financial toxicity as well as like, you know, toxicity just from the drugs themselves. A lot of trials are trying to figure out how to balance all these things and trying to figure out these different patient cohorts, how to optimize treatment as best we can.

Next slide.

[00:43:48]

Transplant-Ineligible Patients

Again, transplant-ineligible, there have been a few different studies that have come out that I think are pretty paradigm-changing for our patients. The three most recent ones are IMROZ, BENEFIT, and CEPHEUS.

IMROZ and CEPHEUS are fairly parallel trial designs. You have your triplet of lenalidomide, bortezomib, dexamethasone versus a quad and with Sanofi's first being isatuximab versus Janssen with daratumumab-based, and you have BENEFIT as well, too, which has been the paradigm myeloid-based regimen of your CD38 with Len-Dex versus the addition of bortezomib with that as well, too.

We will go to the next slide.

[00:44:43]

Tips for Assessing Frailty

Again, tips for assessing frailty. Again, frailty is a little bit subjective. I think you could ask different hematologists, what they would score their ECOG for different patients. I think you get ballparks, but I do not think there would necessarily always be consensus. But also taking into consideration disease burden, is this a transient decrease in their frailty that can be improved with treatment, or is this something that we need to kind of consider long-term?

There are different tools for measuring frailty. They all incorporate different things, and some are kind of more cumbersome than others. But I do think they do have their utility because, again, I think we have a very limited time in a clinic to assess for frailty, and frailty is different. It is like a 15-minute clinic visit versus what they have to participate at home. A lot of times it does take a multidisciplinary approach, like involving PT or your geriatrics clinic or just whatever you think could get you a better assessment.

And I think the primary thing is we should try to keep up the dose density as best as we can for patients. There are a lot of older patients that I think we undertreat for myeloma because we assume they cannot tolerate the treatment, and they may be getting inadequate disease control. But also on the balance, we want to make sure that we are not causing more trouble than good with our treatments because they do have real toxicities and can impair quality of life.

Next slide, please.

[00:46:08]

DRd vs Rd in Transplant-Ineligible NDMM

Again, probably the part I am going to emphasize here is the MAIA trial because I think that has changed a lot of practices here in the United States. Again, it is just the doublet, the lenalidomide-Dex versus DRd and transplant-ineligible multiple myeloma.

Again, higher response rates when you add lenalidomide, I mean, daratumumab to lenalidomide, 92% versus 81%. But the most important thing and why this was just practice-changing is, again, in that median overall survival. So, not reached versus 65 months.

So, we would see a statistically significant difference in overall survival with the addition of daratumumab to lenalidomide for patients that are transplant-ineligible. And did not really see a big safety signal, including increasing risk of side effects with the addition of that medication. And again, the CD38-based regimen improved that MRD negativity as well, too.

Next slide.

[00:47:04]

CEPHEUS: Daratumumab SC + VRd in Patients With NDMM Without Planned Transplantation

Again, CEPHEUS, we talked about this a little bit a second ago. Again, this was your triplet-based regimen versus daratumumab in patients that are going without planned transplantation.

Again, you have a quad, and then the maintenance was Dara, Rd versus Rd. And they stayed on this until toxicity or progressive disease. And again, the primary endpoint, again, was MRD negativity at 10^-5 with key circuit endpoints, PFS, CR. That is all kind of typical. Again, this is a large randomized trial.

Next slide, please.

[00:47:40]

CEPHEUS: PFS and MRD Negativity Rate

And you can see, again, to just demonstrate across a lot of these trials with the addition of a CD38-based regimen, improved progression-free survival, as well as increasing levels of MRD negativity as well. And pretty clear separation occurs there at 54 months, again, 68% versus 49%. As well, too, I think, important is the response in this trial was the safety signal as well.

These patients were frailer patients, older patients that are typically transplant-ineligible. And we do get worried about over-treating these patients, but we did not really see an increase, like, safety signal or concern for increasing toxicity with the addition of another medication, demonstrating that quad-based therapy is feasible and, I think, tolerable and also beneficial in the majority of our transplant-ineligible patients.

Next slide.

[00:48:32]

IMROZ: VRd ± Isatuximab in Transplant-Ineligible NDMM

IMROZ, again, pretty parallel trial design. Again, RVd versus Isa-RVd, and transplant-ineligible. All different key primary endpoint progression-free survival, again, but very similar trial design.

But similar key secondary endpoints, CR rate, MRD negativity rate, overall survival. Again, these are patients that were maybe a little bit more frail by definition, by inclusion. But, again, newly diagnosed by alone, not considered for transplant due to older age or comorbidities.

Next slide, please.

[00:49:12]

IMROZ: PFS and MRD Negativity Rate

Again, very similar parallel results. We are seeing improved progression-free survival in patients that had the addition of isatuximab. Again, our other CD38 antibody in patients that are transplant-ineligible. And deeper rates of MRD negativity across the board in the intend-to-treat population, patients that see a CR, and then also sustained MRD negativity. So, again, addition of these CD38 antibodies improves response and improves the depth of response. It also improves duration in an MRD-negative response. It is really what we are hoping to see for all of our patients.

Again, additionally, no real increased safety signal with these patients as well, too. So, again, demonstrating that this is a very feasible approach for treating the majority of our patients, even patients that are older and not transplant-eligible.

Next slide, please.

[00:50:04]

BENEFIT: Isa-Rd ± Bortezomib in Transplant-Ineligible NDMM

And this is the BENEFIT. Again, this was another kind of quad versus triplet-based. I think this was only a Phase III trial. But the primary endpoint was MRD negativity, 18 months. The comparison in this arm was Isa-Rd versus Isa-bortezomib-Rd. So, again, the addition of Velcade to these regimens as well, too. These are patients that were newly diagnosed with myeloma who are transplant-ineligible, no prior systemic therapy. So, a frontline trial. And, again, for cycles 13 through 18, they got Isa and Velcade. And then cycle 19 onwards, on the frontline, they got isatuximab plus R versus the comparison of just isatuximab plus R and maintenance.

Next slide, please.

[00:50:58]

BENEFIT: Rate of MRD Negativity and ORR in ITT

Again, you can see for the addition of isatuximab, deeper rates of MRD negativity, both at 10^-5 and 10^-6 at 12 months and 18 months. You see that there, although not a little overlap of the confidence intervals, there is a beginning of separation between the two curves and a benefit in PFS at 24 months of 85% versus 80% between the two groups.

Next slide, please.

[00:51:32]

Strategies for Supportive and Equitable Care in NDMM

All right. Strategy for supportive care and equitable care and newly diagnosed with myeloma.

Next slide.

[00:51:40]

Low Enrollment of Black Patients in MM Clinical Trials

So, what has plagued myeloma trials for the longest period of time is I do not think our trials are very representative of our population. We know that African-American patients are very much underrepresented in our trials.

I go to just about every meeting I go to, there is always a presentation on this. We are very good at identifying the problem; we are not very good at fixing it. But we know, again, that our Black patients tend to be very, very underrepresented on these trials.

That has always been a problem because we want our trials to be applicable to the populations we treat. And I think for a large majority of our trials, I do not think they are very representative of our patient population.

Again, the benefits, again, improve access to novel therapies. Trials are more representative. And identification of molecular subtypes that can be targeted by established novel drugs. And then there are some potential patients that, like your – for example, that have the Duffy null phenotype, that is more prevalent in the Black population, that we may see that they benefit more or less from transplant.

And we are starting to understand that more because we have more data, and we are enrolling more patients. But, again, these are just patients that we maybe are not optimizing treatment because we just are not identifying these patients and what makes these patients different from each other. So we still need to work on it.

We can go to the next slide.

[00:53:08]

Supportive Care in Frontline Therapy

Supportive care and frontline. Again, our typical frontline therapy, again, a quad-based regimen, we are combining CD38, proteasome inhibitor, an IMiD and a steroid. Again, typically all these patients get all these drugs as well as some supportive care medicines, including our patients go on antiviral prophylaxis to prevent shingles, usually acyclovir, as well as usually most patients get an aspirin to prevent blood clots due to exposures, like the IMiD use, as well as supportive care with either zoledronic acid or denosumab to reduce the risk of bone-related events. There are some patients that end up going to need growth factor support and things like that.

Multiple myeloma is very pill-burdened and requires a lot of patient education to get patients on it, and it becomes a barrier for compliance because of all the different things we start patients on, not just the drugs to treat the myeloma, but all the drugs that help support to treat those drugs as well, too.

Next slide, please.

[00:54:14]

Infections: Risk and Recommended Management

Again, we kind of talked about this already, too. Again, we do shingles prophylaxis, and one of the biggest things we see long-term is infection issues with patients. So all our patients get our shingles, because a lot of our patients become hypogammaglobulinemia and anemic, especially on our newer therapies like CAR T and bispecifics, we are using a lot of more PJP prophylaxis with like Bactrim, sorry, TMP-SMX, and also using a lot more IgG because of how hypogam they become. And then we do use a fair amount of growth factor as well, too.

Next slide.

[00:54:54]

Additional Considerations: We Treat People, not Myeloma

Additional considerations: we treat people, not myeloma.

Again, so myeloma is a very intensive regimen, and I think it is such a long-term treatment. You often have times people come in for once-a-week treatment for years, which is very disruptive to their weekly routine. They are taking care of patients. They are taking care of people at home or kids or something like that, and they have to figure out alternate regimens to help with that while they are getting treated, as well as it is disruptive to work life and things like that, too, and they have to take off a lot of work. So it can be very disruptive. So there is a lot of financial toxicity, psychological stress.

We do have navigators, and we have our psychological support groups that we encourage enrollment in. Again, and not just treating the patient, but also caregivers as well, too, because no disease exists in a vacuum. Nutrition services, sleep support, and then sexual and reproductive information, especially with our myeloma patients with kind of the REMS program and the need for, you know, all this contraceptive education as well, too, and pregnancy tests every single month.

Next slide.

[00:56:08]

What Are Health Disparities?

What are health disparities? Health disparities are preventable differences in the burden of disease, injury, violence, or opportunities to achieve optimal health that are experienced by socially disadvantaged populations, and health equity is generally first in individuals to achieving their highest level of health through their elimination disparities in health and healthcare.

This is a big active area of research in our institution across as well, too, is the treatment is only as good as how we are able to access patients and get to patients and find ways to get patients to come to our center. So whether that means just having support for rides or support to get the medications they need. It takes a lot for our patients to stay on treatment, especially when they have jobs, kids, caregivers, and all that are a burden outside the four walls of our treatment centers.

Next slide, please.

[00:57:06]

What Are the DRIVERS of Disparities in MM?

What are the drivers of disparities in multiple myeloma? Systemic racism, healthcare system, social determinants of health, biology of disease, and concomitant medical morbidities, delayed diagnosis, access to care, triplets, transplants, clinical trials, CAR T therapy, and then, lack of diversity, cultural sensitivity, and optimal communication among healthcare professionals.

So there, again, these are problems that I think we have identified for long periods of time. And I think all centers are trying to figure out ways to fix these, but it is an ongoing problem. I am not going to say that we certainly do not have all these fixed at Wake by any means, but there are definitely ongoing resources for a lot of our patients, I think, are hopefully, we are getting our access to patients and better care sooner.

Next slide.

[00:57:56]

A Call to Action: Facts About Black Patients and Myeloma

Call to action facts: about Black patient myeloma. So there is a longer time from symptoms to diagnosis among Black patients.

This is your classic patient that has been coming to the ER for weeks with back pain. That is ignored as kind of musculoskeletal, and eventually someone does an image and finds that lytic lesion, and then Black patients tend to be younger at diagnosis. And multiple myeloma tends to be more common in Black patients.

They are less likely to receive the four T's: transplant, triplets, trials, and CAR T. They have biological differences with less high-risk myeloma. Again, like this is another thing, like the Duffy null phenotype, which may influence the treatment response.

Survival outcomes in Black patients are half of what is seen in white patients, and Black patients can achieve equal or better outcomes when they receive therapy. And I really think that that last bullet point is the key point. Like when you get patients here, we get them to treatment. They do well. But we need to focus on how we are getting people in chairs, and how to get them to get seen and get them to get diagnosed. I think we do a good job taking care of our patients, but if they are not getting identified, and they are getting identified later, then we are behind the eight ball.

We need to find ways to get them diagnosed early, and then like kind of prevent those like end-organ damage, like prevention of the bone fractures or dialysis and things like that.

Next slide.

[00:59:20]

Key Tips in Providing Equitable Care

Key tips in providing equitable care:

• Be aware of the causes.
• Understand bias and constantly overcome it.
• Support community engagement.
• Participate in primary care education to facilitate early and accurate diagnosis.
• Practice cultural competence, which leads to enlisting humility, leveraging the multidisciplinary team.
• Be aware of the lack of trust in the healthcare system when it comes to clinical trials.
• Support programs designed to reduce health disparities and myeloma.

And I think one of the things I learned is that when you go out to the community, you cannot just ask for something. You have to offer something, your time, or something that they could, like when you go to these events where you are reaching out for screening, or just helping to identify barriers in the community. I think a lot of times these communities get wary of healthcare coming into the area too, because they tend to just ask for things and want things back.

So what can you offer to them before you start asking for things? But one thing that I also learned, too, is just like, especially when trying to get people on trials, there are times where I try to convince people to get into clinical trials. And I feel like if I feel like I have not convinced people, then if something were to have a bad outcome, then a lot of times it ruins that trust between myself and them.

So I really try to find ways to kind of meet people where they are at, and then make sure that if they want to do something, it is because they feel comfortable doing it. Because again, I want these patients to trust me for years and years. And if I ruin that trust off a trial, they did not feel comfortable. And then I think I have ruined a clinical relationship and may actually like harm their long-term outcomes.

Next slide.

[01:00:52]

Treatment Location Affects Survival in US Patients With MM

Treatment locations affect survival.

So there is data suggests that I think that patients that are seen at academic centers tend to do better with multiple myeloma. I think there are a lot of different reasons for this. I think one of the biggest things is myeloma is only about 1% of all cancers. And I think it is easy for me to kind of sit here when I only treat myeloma to kind of criticize how treatments are outside of the community. But to recognize that, I mean, most people are only seeing like a handful of myeloma patients on their panel versus me, I am seeing one after the other. And myeloma, again, it is not your bread and butter, like your lung or prostate.

So I think a lot of times what I encourage for a lot of our community-based partners is like just refer early. I am more than happy to help, at least see the patient, and make them aware of what is out there. And I think it helps us to just start building these relationships early. We are talking about things like transplant and CAR T. These are intensive therapies. And I think it is hard to see a patient the first time and convince them to do CAR T in the same visit as well, too, when they do not know you. And you are asking a lot of them in terms of caregiver support and kind of what they are like, kind of a highly toxic treatment.

So again, my recommendations usually always refer early to an academic center, even if they are not 100% sure they want to do transplant or CAR T or anything like that, just so they can get looped in and see kind of what is out there. Because again, the treatment landscape for myeloma is changing very rapidly. And there may be some things out there or a trial that they may be eligible for that they were not even aware of.

Next slide.

[01:02:28]

Potential Solutions for Reducing Disparities

Potential solutions for reducing disparities.

Again, broad eligibility criteria. Again, that has been a big issue. It is like we are missing people that had history of polyps or leukemia in the past. Their renal function is too low. Their counts are a little bit too low. And again, we really want patients that are representative of what we are seeing.

And oftentimes, again, trial populations tend to be much healthier and then not always representative of the vast arrays of comorbidities we are seeing in the clinic. Again, clinical trial design study:

• To encompass disease subtypes common to Black patients;
• Appoint diversity offering for local trial site operations;
• Enhance the role of patient navigators, which we have used a lot in our clinic;
• Consistent staff education on valuing different ethnicities in relation to culture;
• Focus on effective communication.

And then overcoming social issues:

• Establish strong patient healthcare relationships by acknowledging and addressing patient concerns;
• Form relationships through outreach;
• Include social groups. This is where we have done a lot of things with church and medical societies. And just, again, meet people where they are at;
• Engage with advocacy groups. You know, a lot of times I go to a lot of the social support groups and myeloma groups in the area just to speak to them;
• Have patient-shared trial experiences with others to alleviate fears, concerns. I have seen this a lot too. I spent a good hour trying to talk to a patient about a trial. They saw someone else in the pod that was on the same trial, and they talked to them for two seconds. They decided to sign on for the trial. Just because they encouraged them to do it. So hearing from someone else they'd gone through was more impactful than anything I could have told them.
• And develop programs to make resources available to clinical trial infrastructure and locations that are race and ethnicity rich.

Next slide.

[01:04:06]

Let's Go Back to Our Questions

All right. Okay. Let us go back to our questions.

[01:04:10]

Posttest 1: Which of the following clinical combinations of characteristics would be consistent with a diagnosis of multiple myeloma that requires treatment in a patient with no evidence of end-organ damage (i.e., CRAB criteria)?

Again, which of the following would be consistent with the diagnosis of multiple myeloma that requires treatment with a patient with no evidence of end-organ damage? So I think this kind of eludes to that slim CRAB criteria I talked about. So patients that do not have any of the CRAB criteria, but have one of those other high-risk features.

1. Clonal plasma cells at 55% and a serum and protein at 2 g/dL, no focal lesions on MRI;
2. Clonal plasma cell at 20% and serum monoclonal protein at 2.5 g/dL, one focal lesion on MRI;
3. Clonal plasma cells at 10%, serum free light chain ratio greater than 100, and no focal lesions on MRI; or
4. Clonal plasma cells at 15%, serum light chains at a ratio of 80 and no focal lesions on MRI.

Speaker: Polling is open.

Dr. McKay: All right. I think that is an improvement. So I think the answer to this would be C. So this is where that SLiM criteria we have the light chain ratio or a 100:1 that would be considered multiple myeloma, even if you do not have the other classic criteria. It is pretty close. So it is greater than 60% would make criteria for myeloma. But again, that 100:1 is kind of that classic one that we are that we are kind of looking for in this question.

[01:05:46]

Yes, so you are getting this ratio of a over 100:1. And B was the caveat that I always have to be greater than 5 mm. But the 100:1 is the one that will get you.

All right, next.

[01:06:06]

Posttest 2: A 75-yr-old man presents with fatigue, weight loss, and new back pain. Labs show a hemoglobin of 9.5 g/dL, serum creatinine of 1.3 mg/dL, and serum protein of 3.8 g/dL. Bone marrow biopsy confirms 50% clonal plasma cells, and he is diagnosed with multiple myeloma. He has controlled hypertension and ECOG PS 1. which would you recommend as most appropriate?

All right. So this is a patient with newly diagnosed multiple myeloma. Again, what would you recommend is the most appropriate?

1. Autologous stem cell transplant;
2. Double therapy such as Rd;
3. Triple therapy such as DRd or VRd; or
4. Quadruple regimen such as D-VRd or isatuximab-VRd.

Speaker: The poll is open.

Dr. McKay: All right. Very good. So I agree.

[01:06:54]

I think hopefully one of the take-home from this talk is that I think, again, the doublet era of myeloma is well and gone. I think we are firmly in the quad-based era. I think what I have seen is that quad-based therapy is very well-tolerated even in patients that are elderly and frail. Even patients that are 75 with some comorbidities tend to do pretty well.

The three different drug classes that we use as the backbone for myeloma, I tend to think the CD38 is probably the easiest and the one I tend to titrate the least. If we had a choice between all the drug classes to begin with and they are all put on at the same time, I think we probably base our therapies off of Dara and off of the CD38s because they are probably the easiest to tolerate of the other drug classes. I think there is very few patients now that I do not start on quad-based therapy. It is more of an exception. Even patients that are not going to transplant because I think they can tolerate it. You can start them at lower doses of Len and things like that. I think I try to figure out reasons to keep people on quad versus not.

All right, next question.

[01:08:10]

Posttest 3: For patients receiving anti-CD38 antibodies, prophylaxis is mandatory in clinical practice for which of the following infections?

All right. For patients receiving anti-CD38 antibodies, prophylaxis is mandatory in clinical practice for which of the following infections?

1. Adenovirus;
2. CMV;
3. Mold;
4. Varicella or like shingles; or
5. Yeast.

Speaker: Polling is open.

Dr. McKay: I Agree. I will take that. I agree with you as well too.

[01:08:50]

So yes, your proteasome inhibitors in your CD38 are going to get your shingles, and then your IMiDs are going to get your VTE prophylaxis, either aspirin or usually a DOAC if they have a higher risk of clotting.

Next slide.

[01:09:10]

Poll 4: Do you plan to make any changes in your clinical practice based on what you learned in today's program?

I will take that.

[01:09:46]

Poll 5: Please take a moment to text in 1 key change that you plan to make in your clinical practice based on this education.

[01:10:02]

Thank You For Attending Our Program!

Q&A

Speaker: Was there any patient who approached you with a question about the suitability of a second stem cell transplant, and what would be the answer to such a proposal?

Dr. McKay: I do not think I have done a second stem cell transplant for a while. I think, to be honest, now that we have CAR T, if they are wanting if they want to do something more intensive, then I would probably opt to do CAR T. I think that is a lot. I mean, I think I did a second transplant for one person. They had been in remission for 10 years after transplant, and had a very slow relapse. So I figured if they got another 10 years or 5-10 years after a second transplant, they did really well with it. But again, I think very few people are going to go through a second stem cell transfer with CAR T. So if they relapse, then you have CAR T available in the second-line. I would probably much rather go through that because, again, you're going through something novel as opposed to Cytoxan chemo again.