Exploring the Results of Elranatamab for Relapsed/Refractory Multiple Myeloma With Noopur Raje, MD

Recently, Dr. Noopur Raje, Director of the Center for Multiple Myeloma at Massachusetts General Hospital, sat down with Oncology Data Advisor at the 64th American Society of Hematology (ASH) Annual Meeting to discuss the results of the MagnetisMM-1 study of elranatamab for multiple myeloma that she presented. Dr. Raje elaborates on the efficacy and safety of this promising agent and highlights the other exciting multiple myeloma research with the potential to change practice in the coming year.

This podcast episode was recorded live by Oncology Data Advisor and ConveyMED at the 2022 ASH Annual Meeting in New Orleans.

Oncology Data Advisor: Welcome to Oncology Data Advisor. Today, I’m at the ASH Annual Meeting with Dr. Noopur Raje. Thanks so much for being here.

Noopur Raje, MD: Thank you for having me.

Oncology Data Advisor: Would you like to introduce yourself and tell us about what you do?

Dr. Raje: Sure, my name is Noopur Raje. I work in Boston. I’m a Professor at Harvard Medical School, and I direct the Multiple Myeloma Program at Massachusetts General, in Boston.

Oncology Data Advisor: I know you have an abstract here about elranatamab for relapsed/refractory multiple myeloma. Would you like to tell us about the study?

Dr. Raje: What I presented was the MagnetisMM-1 study. This was the first in-human trial of elranatamab in relapsed/refractory multiple myeloma patients. What I presented yesterday were data on 55 patients who had reached the maximum tolerated dose (MTD) and the phase 2 dose (≥215 μg/kg). These 55 patients were heavily pretreated patients, as is seen with all the bispecifics. They had received a median of five lines of therapy.

I think what is interesting about the MagnetisMM-1 study is that it is the only B-cell maturation antigen (BCMA) bispecific where we allowed prior BCMA treatment, in the first in-human trial. About 23% of our patients had a prior BCMA. What is notable in this study is the fact that we had a pretty high response rate. The response rate was about 63% in this heavily pretreated patient population, and we had a stringent complete response rate of about 38%.

The majority of our patients had received either an antibody-drug conjugate (ADC), so belantamab mafodotin, or a chimeric antigen receptor (CAR) T-cell therapy, and some of them had received both. The one thing which we did not allow on the study was a prior bispecific, obviously. Notably, we saw a response rate that, albeit a little bit lower, was about 54% in the prior BCMA–treated patient population.

This is really relevant now, given that we have so many different drug products which are BCMA-targeting at this point in time. This high response rate translated nicely into a good duration of response in the responders. We saw that patients responded for up to about 17 months, and the median progression-free survival of this patient population was about 11.5 months. Again, toxicity-wise, it was well tolerated, with the expected toxicity of cytokine release syndrome (CRS), which was mostly grade 1 and 2 and easy to manage.

Oncology Data Advisor. That’s great. Is there any other exciting myeloma research that you’ve seen presented here that you’d like to talk about?

Dr. Raje: I think the meeting is all about bispecifics this year. Bispecifics are getting a lot of attention, and rightfully so. There was one more abstract which was presented with another BCMA bispecific, alnuctamab. The data’s still early, but it looks very similar.

To me, what was exciting were the other targets that were also presented. We saw data with a bispecific against G protein–coupled receptor, class C, group 5, member D (GPRC5D), talquetamab, and that had really high response rates and a good durability of response, approximately nine months or so. Notably, they did see some toxicities of dysgeusia and nail and skin changes, so I think we’ll have to just watch for that a little bit. Another target in the bispecific world is Fc receptor–like protein 5 (FcRH5), so cevostamab is out there. Data with that is being presented as well.

Given that we have our first-in-class bispecific already approved in the context of myeloma, to me what was interesting was a study here looking at using prophylactic tocilizumab to reduce the incidence of CRS. As of right now, what we are doing with all bispecifics is hospitalizing patients for about a week.

If we start using these prophylactic strategies, it’s potentially possible that we are not going to need to use this. It’s going to be a big step forward in terms of how we take care of our patients.

Oncology Data Advisor: So, with all these data being presented, what are you most looking forward to in the next year or so in myeloma treatment?

Dr. Raje: There is also data at this year’s meeting on CAR T cells, and the CAR T cells being brought in earlier. We have the KarMMa-2 data being presented. We’ve seen data with CARTITUDE-2 as well. The hope is that the KarMMa-3 and CARTITUDE-4 data will come up soon. I’m looking forward to seeing CAR T-cells being moved earlier on in the course of treatment for myeloma.

I’m now honestly interested in looking at some of these bispecifics in antibody treatments. We saw an abstract where teclistamab was combined with daratumumab and lenalidomide in the relapsed refractory setting, but the intent there is to bring it up front. Having that trial to try and beat the gold standard of lenalidomide/dexamethasone/daratumumab with this combination, to me, is a step in the right direction. It’s really exciting to see how these immunotherapeutic strategies are moving so much earlier in the course of treatment.

Oncology Data Advisor: Definitely, that’s very exciting. Well, thank you so much for sharing all this. It was great talking with you.

Dr. Raje: Awesome. Thank you.

Thank you for listening to this podcast recorded live at the 2022 ASH Annual Meeting by Oncology Data Advisor and ConveyMED. For more expert perspectives on the latest in cancer research and treatment, be sure to subscribe to the podcast at OncData.com and conveymed.io. Don’t forget to follow us on social media for news, exclusive interviews, and more!

About Dr. Raje

Noopur Raje, MD, is the Director of the Center for Multiple Myeloma at Massachusetts General Cancer Center and a Professor of Medicine at Harvard Medical School. Her research interests include understanding the biology of multiple myeloma, including the roles of B-cell activating factor and cyclin D dysregulation, as well as the biology of bone disease in multiple myeloma. In addition, Dr. Raje’s translational research focuses on the development of novel therapeutics for the treatment of multiple myeloma, including ADCs and small molecule inhibitors. She has authored or coauthored numerous publications in peer-reviewed journals.

For More Information

Raje N, Bahlis NJ, Costello C, et al (2022). Elranatamab, a BCMA targeted T-cell engaging bispecific antibody, induces durable clinical and molecular responses for patients with relapsed or refractory multiple myeloma [oral presentation]. 64th American Society of Hematology Annual Meeting. Abstract 158.

Wong SW, Bar N, Paris L, et al (2022). Alnuctamab (ALNUC; BMS-986349; CC-93269), a B-cell maturation antigen (BCMA) x CD3 T-cell engager (TCE) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): results from a phase 1 first-in-human clinical study [oral presentation]. 64th American Society of Hematology Annual Meeting. Abstract 162.

Chari A, Touzeau C, Schinke C, et al (2022). Talquetamab, a G protein–coupled receptor family C group 5 member D x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM): phase 1/2 results from MonumenTAL-1 [oral presentation]. 64th American Society of Hematology Annual Meeting. Abstract 157.

Lesokhin AM, Richter J, Trudel S, et al (2022). Enduring responses after 1-year, fixed-duration cevostamab therapy in patients with relapsed/refractory multiple myeloma: early experience from a phase I study [oral presentation]. 64th American Society of Hematology Annual Meeting. Abstract 1924.

Yao JM, Kim H, Yang D, et al (2022). Tocilizumab for the management of cytokine release syndrome after haploidentical hematopoietic transplant with post-transplant cyclophosphamide-based GvHD prophylaxis [oral presentation]. 64th American Society of Hematology Annual Meeting. Abstract 3374.

Ferreri CJ, Hildebrandt MAT, Hashmi H, et al (2022). Idecabtagene vicleucel (ide-cel) chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory multiple myeloma (RRMM) who have received a prior BCMA-targeted therapy: real world, multi-institutional experience [oral presentation]. 64th American Society of Hematology Annual Meeting. Abstract 766.

Van de Donk NWCJ, Agha M, Cohen AD, et al (2022). Ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR-T cell therapy, in patients with multiple myeloma (MM) and early relapse after initial therapy: CARTITUDE-2 Cohort B 18-month follow-up [oral presentation]. 64th American Society of Hematology Annual Meeting. Abstract 3354.

Searle E, Quach H, Wong SW, et al (2022). Teclistamab in combination with subcutaneous daratumumab and lenalidomide in patients with multiple myeloma: results from one cohort of MajesTEC-2, a phase 1b, multicohort study. [oral presentation]. 64th American Society of Hematology Annual Meeting. Abstract 160.

Transcript edited for clarity. Any views expressed above are the speaker’s own and do not necessarily reflect those of Oncology Data Advisor. 

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