Evaluating Treatment Options for Patients With Relapsed/Refractory Multiple Myeloma

Noa Biran, MD, Hackensack Meridian Health, Hackensack, New Jersey, evaluates a variety of treatment options for patients with relapsed/refractory multiple myeloma, a topic which she presented on at the 2024 Great Debates & Updates (GDU) in Hematologic Malignancies meeting in New York, New York. 

Transcript:

Hi, my name is Noa Biran. I'm an associate professor of medicine at Hackensack Meridian Health School of Medicine at the John Theurer Cancer Center. I work in the division of multiple myeloma.

Today, I'll be talking about a talk that I gave at the Great Debates [and Updates in Hematologic Malignancies meeting] in New York this past weekend on the topic of relapsed/refractory multiple myeloma.

We're very lucky in our field and in treating our patients in that we have a variety of treatment options for patients in the relapsed/refractory setting. I think what is most important is to break down our patients into early versus late relapse. In the early relapse setting, we have patients who are eligible for 3 major classes of drugs: monoclonal antibodies, proteasome inhibitors, and [immunomodulatory drugs] (IMiDs). I think we can do a variety of treatment options with daratumumab-based therapy [and] isatuximab-based therapy, combined either with IMiDs or proteasome inhibitor.

What's notable is data from the IKEMA study that had the lowest hazard ratio in terms of [progression-free survival] (PFS) for patients with early relapsed myeloma and showed that the combination of isatuximab, carfilzomib, and dex[amethasone] was superior to the combination of carfilzomib and dex[amethasone]. That's a very effective option in patients who are relapsing after first induction or first transplant. Then, we get into some other options for early relapse, which include small molecule inhibitors, such as selinexor, or in the case of patients who have the t(11;14) translocation, venetoclax.

Once patients relapse after 1, 2, or 3 prior lines of therapy, they become what's considered triple-refractory. And these patients are refractory to the 3 most commonly used classes of drugs, monoclonal antibodies against CD38, IMiDs, and proteasome inhibitors. Their life expectancy historically has been much shorter and their response rates to therapies once they're triple refractory historically ha[ve] been around 30%.

Luckily, that has changed with now our chimeric antigen receptor (CAR) T-cell therapies as well as our bispecific T-cell engagers. We have 3 FDA-approved bispecific T-cell engagers [and] 2 of them target [B-cell maturation antigen] (BCMA) and [cluster of differentiation 3] (CD3), those are elranatamab and teclistamab. Those drugs have response rates nearing 60% among all patients in that triple-class refractory setting, which is very positive and good results for our patients.

Toxicities from the bispecifics in general include cytokine release syndrome and [immune effector cell-associated neurotoxicity syndrome] (ICANS), which is neurotoxicity from cytokine release, and we have to treat those patients in a step-up dosing fashion in the hospital before they achieve a therapeutic dose of [the] drug, and then those patients can be transitioned into the outpatient setting.

The 3rd bispecific T-cell engager is talquetamab, which targets both CD3 and [G protein-coupled receptor class C group 5 member D] (GPRC5D), which is a surface receptor on malignant plasma cells. That one has slightly less risk of infections compared to the BCMA bispecifics, but it does have some toxicity involving skin and taste changes, which have to be monitored and can increase with time.

The next class of drugs that's very effective in the triple-class refractory state is the CAR T-cell [therapies]. We have 2: [idecabtagene vicleucel] (ide-cel) and [ciltacabtagene autoleucel] (cita-cel), which as of last week have been approved for early relapse. So, patients who are lenalidomide-refractory and have had 1 prior line of therapy can receive cilta-cel. And, patients who have had 2 or more prior lines of therapy and have been exposed to both proteasome inhibitor, IMiD, and monoclonal antibodies are eligible for ide-cel.

Both of these therapies require apheresis of the T-cells with approximately a 6- to 8-week waiting period. And then, for those T-cells to be genetically manufactured, and then the cells are re-infused. Similarly to the bispecifics, we have to watch for cytokine release syndrome that occurs at a rate of 85% among patients receiving CAR T-cells, but most of those are not severe in nature and can be managed with tocilizumab and steroids.

Furthermore, we have to watch for [the] risk of infection in these patients for the long term. So, relapsed/refractory myeloma is now becoming more of a chronic disease where we have a whole host of therapies. The number of different treatments i[s] increasing with more robust, by specific T-cell engagers and CAR T-cells and clinical trials. It's about playing a chess game and figuring out how to best use each treatment and when. Thank you.

Source:

Biran N. Relapsed/Refractory Multiple Myeloma: Essential Strategies to Optimize the Utility of Novel and Cellular Therapies. Presented at the 2024 Great Debates & Updates in Hematological Malignancies: April 5-6, 2024. New York, NY.