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Overview of Multiple Myeloma
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Physician Assistants/Physician Associates: 0.25 AAPA Category 1 CME credit

Pharmacists: 0.25 contact hour (0.025 CEUs)

Physicians: maximum of 0.25 AMA PRA Category 1 Credit™

Nurse Practitioners/Nurses: 0.25 Nursing contact hour

Released: March 17, 2026

Expiration: September 16, 2026

Doris K. Hansen
Doris K. Hansen, MD

We know that multiple myeloma at this time is not a curable disease, but it is very much a treatable disease. So, certainly the treatment is a marathon. It is not a sprint, as it says there. And myeloma may start as MGUS, or it can be smoldering. And ultimately, patients might relapse, and they require multiple different lines of therapy. But generally, we know attrition rates are high, and these immunotherapies have proven to be quite impressive in terms of improving outcomes for our patients.

 

Next slide, please.

 

[00:11:06]

 

Treatment Goals and When to Initiate Therapy at Relapse

 

Now, treatment really depends on the type of relapse that our patients are experiencing. So, if you look there to the left, we want to establish disease control. We want to improve efficacy and durability of response for our patients. But certainly, we want to maintain quality of life, and really we want to keep in check the toxicity profile.

 

So, when we look to the right, if somebody's asymptomatic and has a very indolent biochemical relapse, well, generally, we might be able to observe these patients for some time. If they have high-risk or rapid disease progression, well, certainly we need to think about what treatment might be best suited for these patients and then target certain different, for example, if it is t(11;14), we might consider venetoclax. Or if they have a plasmacytoma, we might give radiation.

 

But truly, if somebody's rapidly progressive and they have symptomatic disease, then most certainly we are going to have to initiate treatment and probably more aggressive treatment for those type of patients.

 

Next slide, please.

 

[00:12:10]

 

Novel Therapies in Multiple Myeloma

 

In myeloma, I like to say we have an embarrassment of riches. Unlike, for example, leukemia, we have had a lot of exciting new therapies. I mean, daratumumab, 2015. Subsequently, we had our first CAR T-cell approval in myeloma in 2021, our second in 2022 of ciltacabtagene autoleucel. And then we had bispecific antibodies. Teclistamab was first in 2022. Then we had talquetamab and elranatamab. Most recently, we had another BCMA-directed bispecific antibody, linvoseltamab, which was approved in July. And we had re-approval of belantamab mafodotin, which is an antibody-drug conjugate, very recently in the last few months.

 

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[00:12:54]

 

InterACT Case 1

 

Here is a patient case. This is a 72-year-old man who was diagnosed 10 years ago, and he had standard-risk multiple myeloma. He has CAD, hypertension, diabetes.

 

In terms of his treatment history, he has had VRD, followed by transplant and lenalidomide, and did well for about five years. Subsequently, the patient received Dara-bortezomib-dexamethasone, and this lasted for about 2.5 years. And then elotuzumab-pomalidomide-dexamethasone, and then carfilzomib-cyclophosphamide-dexamethasone.

 

With each course of treatment, the duration of response is less. So, now the patient is relapsing. So, essentially, we have this patient who has had four prior lines of therapy, and now they are relapsing.

 

Next slide, please.

 

[00:13:42]

 

Poll 4: Which of the following would you recommend as the next step in the care of this patient?

 

Which of the following would you recommend as the next step in the care of this patient?

 

  1. Start belantamab mafodotin/bortezomib/dexamethasone (BVd) with an ophthalmology consult;
  2. Start a bispecific antibody with step-up dosing;
  3. Refer the patient to the nearest CAR T-cell treatment center for evaluation; or
  4. Ask the patient about their daily activities, treatment goals, and therapy preferences?

 

I do not know that this is such a fair question, because I feel like any of these could be considerations, but I would like to see what your option would be.

 

Yes, precisely, right? We are speaking about bispecifics. So, certainly, B is appropriate to your patients. Generally, the current approval is four or more prior lines of therapy and triple-class exposure, though I do not believe it is wrong to consider some of these other options and also share decision-making with the patients about what are their goals, what are their therapy preferences, and things like that.

 

Next slide, please.

 

[00:15:02]

 

Bispecific Antibodies in MM

 

Bispecific antibodies are a type of immunotherapy different from CAR T-cell therapy. These are readily available off the shelf. They target CD3 on the T-cell, and depending on which target, we have BCMA and GPRC5D bispecific antibodies, at least at the present time.

 

We have three BCMA-directed bispecific antibodies, as you see there at the bottom. We have teclistamab, elranatamab, linvoseltamab, all of which are currently approved after four or more prior lines of therapy and triple-class exposure to an immune-modulatory drug, a proteasome inhibitor, and a CD38 monoclonal antibody. The only GPRC5D-directed bispecific antibody is talquetamab with the same indication in terms of lines of therapy.

 

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[00:15:52]

 

Considerations for Selecting Treatment

 

So, certainly when we think about treatment selection for our patients, and I think this will become more and more important now that we are going to have multiple BCMA agents that will be approved in early line, we have to think about patient characteristics. Their age, their frailty, their comorbidities. We have to think about the disease. Do they have high-risk disease? Do they have functional high-risk? Do they have extramedullary disease? Do they have high-risk cytogenetics? What are the kinetics of relapse? Are they rapidly progressing?

 

We have to think about regimens. What have they been exposed to in the past? What is their disease responding to? Do they have treatment refractoriness to certain agents? And certainly we have to think about toxicities, right? We think about cytopenias, infections, immune toxicity, CRS, ICANS, non-ICANS toxicities. Now we have a new entity of IEC colitis with CAR T. So certainly all of these are considerations when we choose our next line of therapy.

 

Next slide, please.

 

[00:16:48]

 

Targets for Bispecific Antibody Therapy in MM

 

As I mentioned, we really have BCMA and GPRC5D bispecific antibodies. BCMA is expressed on normal and malignant plasma cells. And then GPRC5D, which is a little bit interesting, is expressed on myeloma cells, but also on hard keratinized epithelium. So that is why patients will have these on-target, off-tumor toxicities, basically on hair and epithelial cells. So patients will have skin rashes. They will have nail changes. They might have dysgeusia and weight loss. We can talk about that in a little bit more detail shortly.

 

So next slide, please.

 

[00:17:27]

 

Efficacy of Bispecific Antibodies in R/R MM

 

So here we have the efficacy of our BCMA and GPRC5D bispecific antibodies. Generally speaking, the response rate ranges somewhere between 61-74%. So fairly similar, I would say. The median progression-free survival is somewhere between 11-17 months, though in the most recently approved linvoseltamab, the median PFS was not reached in that cohort. But generally speaking, really the message is that bispecifics lead to high response rate and durable responses, which is impressive.

 

Next slide, please.

 

[00:18:01]

 

Comparing Bispecific Antibodies for R/R MM

 

So here we show the comparison of the different bispecific antibodies. We are going to go into this in more detail.

 

But importantly, for example, route of administration, for example, Tec, Elra, talquetamab, these are all subcutaneous. Linvoseltamab is the only one that is intravenous. And then dosing is going to slightly vary between them, and we will go over step-up dosing in a minute.

 

CRS generally is common, but mostly grade 1. And these patients are much less likely to develop ICANS compared, for example, to CAR T, but they are more likely to develop infections. So that is something that we have to really support and continue, for example, IVIG and supportive measures for our patients.

 

And then we talked briefly about GPRC5D. This is going to be more of this on-target, off-tumor with skin, nail, or oral toxicities.

 

So, new directions.

 

Next slide.

 

[00:46:16]

 

MajesTEC-3: Teclistamab + Daratumumab vs Daratumumab-Based Regimens in R/R Multiple Myeloma

 

This is some new data. We will discuss a few new data that was recently presented.

 

Some of you voted about giving bispecifics initially early in lines of therapy. You are also not wrong. So, this is based on MajesTEC-3 data.

 

This was recently published and presented at ASH and published in the New England Journal of Medicine, comparing 1-3 prior lines of therapy in patients who were IMiD and PI exposed, though only 5% were daratumumab- or CD38-exposed, comparing to teclistamab-daratumumab with daratumumab-based combinations, as you see there, daratumumab, pomalidomide, dexamethasone, or daratumumab, bortezomib, dexamethasone. And the primary endpoint was progression-free survival. This was a 1:1 randomization Phase III study.

 

Next slide, please.

 

[00:47:06]

 

MajesTEC-3: PFS

 

We saw significant improvement in progression-free survival with Tec-Dara compared to daratumumab-based combinations. What is really impressive is the hazard ratio of 0.17, which is really unheard of. So, quite impressive in terms of efficacy and durability of response.

 

Next slide, please.

 

[00:47:27]

 

RedirecTT-1: Talquetamab + Teclistamab in R/R Multiple Myeloma With Extramedullary Disease

 

Another population of significant unmet need in multiple myeloma, I would say, is our patients with high risk, and one of those is extramedullary disease. Generally, no matter what you give these patients, they are going to have inferior outcomes. So, the RedirecTT-1 study was a combination of talquetamab and teclistamab.

 

The Phase II data was also recently presented and published also in the New England Journal of Medicine, but basically, this is a single-arm study for patients who had true extramedullary disease, and they received basically Tec and talquetamab. As you see there, the primary endpoint being overall response rate, and then the secondary endpoint being more of the long-term PF/OS and durability of response.

 

Next slide, please.

 

[00:48:15]

 

RedirecTT-1: Efficacy

 

And very impressive data, actually, with RedirecTT. I mean, this is what we do for patients, for example, who fail CAR T. We give them Tec and Tal if they have EMD. But the overall response rate, nearly 80%. Complete remission rate over 50%, which is really, really quite great. And then the median PFS of 15 months, which is unheard of in this patient population.