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Adopting the Latest Guidelines in MM
FAQs: Adopting the Latest Guidelines in MM

Released: July 08, 2026

Natalie S. Callander
Natalie S. Callander, MD
Carol Ann Huff
Carol Ann Huff, MD
Mark A. Schroeder
Mark A. Schroeder, MD, MSCI
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Key Takeaways
  • Quadruplet regimens are rapidly becoming standard of care for patients with newly diagnosed multiple myeloma (MM); however, this will create new real-world challenges, especially for patients with double-refractory disease following frontline quadruplet therapy.
  • For patients with MM older than 80 years of age, the choice of frontline treatment using a triplet or quadruplet regimen should reflect their level of frailty and fitness.
  • The future treatment paradigm in MM is likely to see a shift toward use of immunotherapies, including CAR T-cell therapy and bispecific antibodies, earlier in the course of the disease.

In this commentary, 3 experts who serve on the National Comprehensive Cancer Network (NCCN) Multiple Myeloma (MM) guideline panel, Natalie S. Callander, MD, Carol Ann Huff, MD, and Mark A. Schroeder, MD, MSCI, address key questions posed by the audience during a recent symposium held in conjunction with the 2026 ASCO Annual Meeting titled, “Myeloma Masterclass: Adopting the Latest Guidelines for Evidence-Based, Equitable Care”. During this symposium, the experts discussed the latest clinical developments and provided clinical guidance focusing on recent and emerging treatment advances in the personalization of care of patients with smoldering and symptomatic MM.

What are the clinical implications of the recent updates to the NCCN guidelines for the upfront treatment of patients with newly diagnosed MM?

Natalie S. Callander, MD:
With the rapidly adopted use of quadruplet regimens as first-line therapy, we will soon be seeing patients with double-refractory MM (with lenalidomide and anti-CD38 monoclonal antibody refractory disease) in our clinics. Some of these patients may also have undergone autologous stem cell transplant (ASCT), whereas for some, ASCT was deferred or, in some cases, the patient is transplant ineligible. Unfortunately, many current trials do not yet reflect these real-world patient populations, making the selection of optimal evidence-based next-line of therapy challenging.

Mark A. Schroeder, MD, MSCI:
I agree. For patients with lenalidomide-refractory MM after first-line therapy, next-line treatment with a bispecific antibody or CAR T-cell therapy plays a major role. In my clinical practice, I would consider CAR T-cell therapy after relapse on first-line therapy for most of my patients.

Carol Ann Huff, MD:
I also agree. The field is rapidly evolving with the swift integration of quadruplet regimens into the first-line MM setting. The arising question now points to what the optimal next line of therapy should be after a patient has received a quadruplet regimen. Currently, we have very limited evidence from clinical trials to support the optimal choice of next-line therapy in this setting.

How do you decide whether quadruplet therapy is an appropriate primary treatment for patients older than 80 years of age?

Carol Ann Huff, MD:
Validated frailty scores should be used as a tool to guide treatment decision-making. Most of my patients older than 80 years of age are able to receive triplet therapy with daratumumab plus lenalidomide and dexamethasone. However, for those older than 80 years of age who are otherwise healthy and fit, I would favor quadruplet therapy with the addition of a proteasome inhibitor.

Natalie S. Callander, MD:
The ongoing phase III ECOG-EAA181 (EQUATE) trial is comparing the efficacy and safety of the quadruplet regimen containing daratumumab, bortezomib, lenalidomide, and dexamethasone vs the triplet regimen of daratumumab, lenalidomide, and dexamethasone for patients 18 years of age or older who are newly diagnosed with MM for whom there is no intention to undergo early ASCT (NCT04566328). In this trial, all patients will receive 9 induction cycles of daratumumab, lenalidomide, and dexamethasone before randomization based on measurable residual disease status to either continue to receive the triplet regimen alone or in combination with bortezomib for another 9 cycles as consolidation therapy. Thereafter, patients will receive long-term treatment with daratumumab and lenalidomide as maintenance therapy until disease progression or unacceptable toxicity. This is an important study that will help to determine whether the addition of a proteasome inhibitor, in this case bortezomib, improves benefit for transplant-ineligible patients with previously untreated MM.

Which dosing schedule for belantamab mafodotin do you use to prevent ocular toxicities?

Natalie S. Callander, MD:
In my institution, we have long-term experience with belantamab mafodotin because we participated in the initial DREAMM studies of belantamab mafodotin for patients with MM. We have found it to be a very useful drug. For patients on the initial DREAMM trials, we treated patients at the recommended starting dose of 2.5 mg/kg every 3 weeks for 12 weeks. We have had some patients who have received belantamab mafodotin on the extended use program with the administration of biannual infusions and have achieved a sustained remission.

Carol Ann Huff, MD:
In my practice, I tend to begin treatment with the recommended dose with close monitoring for toxicity. Over time, the interval between doses often has to be lengthened, and some patients have achieved sustained remissions on dosing once every 3 months or even less frequently. For grade 2 or 3 ocular toxicity, treatment should be held with close monitoring until symptom resolution to grade 1 or less. Thereafter, treatment should be restarted at the reduced dose of 1.9 mg/kg every 3 weeks. When recurrent grade 2 or 3 ocular toxicities occur, treatment should be withheld until grade 1 or less and reinitiated at the reduced dose of 1.9 mg/kg every 8 weeks. If grade 4 ocular toxicities occur, treatment should immediately be permanently discontinued. It is very important to carefully balance efficacy with toxicity and quality of life concerns before making treatment decisions for patients.

Mark A. Schroeder, MD, MSCI:
In my clinical practice, I seldom use belantamab mafodotin. However, it appears that using the less frequent dosing schedule every 8 weeks significantly reduces the risk of ocular toxicity without impacting efficacy.

What are your thoughts on how the treatment of MM will change in the near future?

Natalie S. Callander, MD:
There are several ongoing trials with the potential to change clinical practice. In the newly diagnosed MM setting, CARTITUDE-5, a phase III trial, is investigating bortezomib plus lenalidomide and dexamethasone followed by ciltacabtagene autoleucel, a BCMA-directed CAR T-cell therapy, vs bortezomib plus lenalidomide and dexamethasone followed by lenalidomide and dexamethasone for patients for whom ASCT is not planned (NCT04923893). For ASCT-eligible patients, the phase III CARTITUDE-6 trial is investigating daratumumab, bortezomib, lenalidomide, and dexamethasone followed by ciltacabtagene autoleucel vs daratumumab plus bortezomib, lenalidomide, and dexamethasone followed by ASCT for newly diagnosed patients with MM (NCT05257083). These 2 trials will help to clearly define the role and utility of ASCT in the newly diagnosed MM setting. Also, the earlier use of bispecific antibodies in MM is being investigated. For instance, the phase III MajesTEC-4 trial is evaluating single-agent lenalidomide or teclistamab vs the combination of lenalidomide and teclistamab as maintenance therapy for patients with newly diagnosed MM following ASCT (NCT05243797).

These interesting trials will shape the future in the care of our patients with MM, and I am looking forward to seeing the results.

Mark A. Schroeder, MD, MSCI:
Immunotherapy, including bispecific antibodies, is increasingly being studied in the newly diagnosed MM setting. For example, the phase II LINKER-MM8 trial is investigating linvoseltamab in combination with bortezomib and lenalidomide vs daratumumab in combination with bortezomib, lenalidomide, and dexamethasone for transplant-eligible patients with previously untreated MM (NCT07428369). Of interest, LINKER-MM8 is also investigating whether there is a need to undergo ASCT after a patient has received first-line therapy with linvoseltamab plus bortezomib and lenalidomide.

The future remains bright for our patients with MM, with the high potential that bispecific antibodies and CAR T-cell therapy will soon be moved into the first-line setting, especially for patients with high-risk disease. These times are exciting as the treatment algorithm continues to evolve.

Carol Ann Huff, MD:
I agree. In the near future, we will need to determine what the next line of therapy should be after disease progression following first-line use of CAR T-cell therapy. For those who do not achieve complete remissions with CAR T-cell therapy, we will need to determine how best to deepen and extend the duration of these responses potentially with CELMoDs and/or bispecific antibodies.

Your Thoughts?
What questions do you have regarding optimizing the use of newer therapies such as belantamab mafodotin and bispecific antibodies in the care of your patients with MM? Answer the polling question and join the conversation in the discussion box below.

Coming Soon! Watch for our new Interactive Decision Support Tool for R/R MM. With just a few clicks to answer a few quick questions about your actual or hypothetical patient, we will show you how your approach compares with treatment recommendations from 5 experts!

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