Updates in Novel and Cellular Therapies for Patients With R/R Multiple Myeloma  

At the 2024 Great Debates and Updates (GDU) meeting in Los Angeles, California, Jonathan Kaufman, MD, Emory University, Atlanta, Georgia, discusses recent updates and optimal strategies for treating patients with relapsed/refractory multiple myeloma with new and immune cellular therapies.

Transcript:

Hi, my name is Jonathan Kaufman. I'm a professor of hematology and medical oncology at Emory University in Atlanta, Georgia, and I'm here today at GDU 2024 in Los Angeles. I'll be presenting on updates in relapsed/refractory myeloma, focusing on new and immune and cellular therapies.

The first update that I'm giving today is reiterating the role of multiple triplets in the management of myeloma, oftentimes a monoclonal antibody targeting CD38 in combination with a proteasome inhibitor or an immunomodulatory agent. The most common treatments we give are daratumumab or isatuximab in combination with either pomalidomide or carfilzomib.

There are a new class of drugs that's being developed called the [Cereblon E3 Ligase Modulatory Drugs] (CELMods). They're very similar to the [Immunomodulatory drugs] (IMiDs) in terms of their molecular structure, iberdomide and mezigdomide. There's now preliminary data that these medications are effective even in patients who are refractory to lenalidomide and pomalidomide, mezigdomide in particular in combination with dexamethasone was very effective. We even saw evidence of benefit in patients who have extramedullary disease. We have to be very conscientious when we use mezigdomide because one of the major side effects of mezigdomide is the development of neutropenia.

Over the past several years, we've had significant advances in myeloma in the relapsed setting with the use of immune-targeted therapies, both bispecific as well as our CAR T-cell therapies. From a bispecific perspective, we now have 2 targets: BCMA, as well as the GPRC5D. There's 2 approved products, teclisatmab and elranatamb. They are both effective in patients with relapsed/refractory myeloma with response rates approximately 60%.

The major toxicity outside of the initial [cytokine release syndrome] CRS and neurologic toxicity that can happen is the development of infections with BCMA-bispecific antibodies. We have as a community gotten much better at managing infections and primarily early use of [intravenous immunoglobulin] (IVIG) for patients who have hypogammaglobulinemia, [immunoglobulins] (IG) levels less than 400, and nearly all patients who are on BCMA-bispecifics do get hypogammaglobulinemia. It's very critical to monitor and to come up with a preventative strategy for the BCMA-targeted bispecifics.

From a GPRC5D [perspective], we have talquetamab. Talquetamab is a very potent medication, response rate closer to 70%. The GPRC5D has less infection risk than associated with the BCMA bispecifics, but it has on-target off-tumor toxicities, primarily taste changes, dysgeusia, skin changes, rash, nail changes, weight loss. It's very important to know about these toxicities and help the patients manage these toxicities.

Finally, over the past several years, we've had the development of CAR T-cells. We have a CAR T-cells, ide-cel and cilta-cel, both target BCMA. They were both approved initially for patients who had greater than 4 lines of prior therapy. And now they moved up earlier in the course of therapy with the KarMMa-3 study in patients who've had 2 prior lines of therapy at least, and the CARTITUDE-4 study in the patients who have had 1 prior line of therapy. Both studies show an improvement in progression-free survival versus standard of care. We're really in a massive shift right now in the relapsed/refractory setting, trying to understand the optimal time to use CAR T-cell therapies.

Source:

Kaufman J. Relapsed/Refractory Multiple Myeloma: Essential Strategies to Optimize the Utility of Novel and Cellular Therapies. Presented at the Great Debates and Updates in Hematologic Malignancies Meeting; July 27-28, 2024; Los Angeles, California.