Saad Usmani, MD, MBA, FACP, discusses the MagnetisMM-1 trial data evaluating elranatamab in patients with relapsed or refractory multiple myeloma (RRMM) and reviews innovations that are needed to improve the management of RRMM.
Saad Usmani, MD, MBA, FACP: The MagnetisMM-1 trial looked at the safety and efficacy of elranatamab in patients who have relapsed/refractory multiple myeloma. This study was reported on for the first time last year, showing overall response rates of well over 60%. At that time, the follow-up for the trial was shorter. At ASH [the American Society of Hematology annual meeting] this year, Noopur Raje, [MD,] reported on elranatamab, and this was a dose-escalation study looking at various doses of elranatamab given subcutaneously, starting from 80 to 1000 µg/kg, given either weekly or every 2 weeks. They looked at safety and the PK/PD [pharmacokinetics/pharmacodynamics] in this particular intervention. Elranatamab is a BCMA-directed bispecific antibody, and this data set also included patients who had prior BCMA-targeted therapies, mostly antibody-drug conjugates [ADCs], as well as CAR [chimeric antigen receptor] T-cell therapies. There were some patients, I think 13 of the 55 patients reported on, and who had both an ADC and a CAR T given in a previous line of treatment.
What was very encouraging to see, we have a follow-up of about 12 months now on this study, and 56% of the patients had a partial response or better. If we look at the median duration of response, that appears to be around 17 months. Several BCMA bispecifics were reported at ASH, and the elranatamab data looked really good. We already have one BCMA bispecific that has been both FDA and EMA [European Medicines Agency] approved earlier this year. I don’t think elranatamab will be far behind in terms of its regulatory approval, hopefully sometime next year.
I think when defining the duration of treatment, we have been talking about this for the past year and a half or so. Now that we have all these newer therapies, the bispecifics and the CAR Ts that are even in the relapsed/refractory state providing a very good depth of response, MRD [minimal residual disease] negativity, which is sustained even at the 10-6 level, we have to start thinking about designing clinical trials that define the duration of treatment. We are already planning several studies in the US cooperative group mechanism to that end. Other cooperative groups both in the United States and Europe are looking at this particular issue as well. I think from a clinical investigator and researcher standpoint, we have to start moving in that direction. From a regulatory standpoint, I think it will be a more difficult task to have regulators aligned with that sustained MRD negativity as a regulatory end point, but if we generate good data that help support that, I think we’d be able to do it. Over the next 5 to 10 years, I think the big innovation would be how we combine these therapies, the BCMA- and GPRC5D-directed therapies, into frontline strategies for a fixed duration, with the goal of sustained MRD negativity. We’ll see many more data sets coming out in the next 5 to 10 years highlighting that.
We have seen for well over the past 4 years, a focus on BCMA-directed therapies, both chimeric antigen receptor T cells and bispecifics. It was really good to see more therapies targeting GPRC5D, that’s a relatively new kid on the block. My colleague, Sham Mailankody, [MD,] reported on the GPRC5D CAR T-cell therapy, a study from MSK [Memorial Sloan Kettering Cancer Center] last year, and now we have 2 bispecifics and another CAR T construct that were presented at ASH this year. The talquetamab data just came out at the right time around ASH as well. I think GPRC- targeted therapies are the eye-catcher we have to look out for.
The other data sets I was interested in include the iStopMM screening study from Iceland. There were several abstracts presented from that data set. There was a very interesting algorithmic abstract presented on how to distinguish patients who may need a bone marrow biopsy when they have MGUS [monoclonal gammopathy of undetermined significance] vs those who may not. I’m looking forward to getting more details about how that algorithm can be utilized by the myeloma community at large. Those are some of the interesting abstracts that caught my eye.
Transcript edited for clarity.