B-cell maturation antigen targeted CD3-engaging bispecific molecule for relapsed or refractory multiple myeloma

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Published: 18 Sep 2021
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Prof Bhagirathbhai Dholaria - Vanderbilt University Medical Center, Nashville, USA

Prof Bhagirathbhai Dholaria speaks to ecancer about the B-cell maturation antigen (BCMA) targeted CD3-engaging bispecific molecule, for patients with relapsed or refractory multiple myeloma. Initially, he discusses the background of the study. Prof Dholaria then explains the methodology and key results. He concludes by talking about the impact these results can have on the future treatment of refractory multiple myeloma.

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

18th International Myeloma Workshop

B-cell maturation antigen targeted CD3-engaging bispecific molecule for relapsed or refractory multiple myeloma

Prof Bhagirathbhai Dholaria - Vanderbilt University Medical Center, Nashville, USA

MagnetisMM-1 is a phase I multipart study basically evaluating the safety of this new bispecific antibody, elranatamab, which targets the B-cell maturation antigen on the myeloma cells and CD3 on the host T-cells. So that’s pretty much the background. We tested this drug on a number of patients with relapsed or refractory multiple myeloma.

It was a phase I study and in part 1 we treated around 30 patients at the different dose levels to show the safety and also find the recommended phase II dose. We found a good number of patients who developed cytokine release syndrome so part 1.1 was opened where a priming dose was introduced and we presented the outcome at IMW on 20 of those patients who received a drug with a priming dose. We also presented the results of part 1c which is a combination arm of elranatamab with lenalidomide. It’s still a little bit early, we presented the outcome for four patients.

The key finding was that overall, across the board, the drug appears to be safe. There was no DLT reported in part 1 of the study and the recommended phase II dose was determined to be 1,000μg/kg. We also learned that the cytokine release syndrome was quite common but most of the CRS events were grade 1 or 2 and they were only seen during cycle 1 of the study. So subsequently patients tolerated the treatment well without any ongoing cytokine release syndromes. There were no significant neurotoxicity events reported.

Another key finding was that at the efficacious dose of greater than 215μg/kg the overall response rate was around 73%. At the recommended phase II dose, which is 1,000μg/kg, the overall response rate was 83.3%.

We also learned that there were a handful of patients who had prior exposure to BCMA-directed therapies such as BCMA monoclonal antibody conjugates such as belantamab and BCMA-targeting CAR T-cell therapy. Out of those four patients three patients responded to elranatamab.

The drug in combination with lenalidomide was also determined to be safe although only four patients’ data but overall there were no new safety signals and the overall response rates were also comparable to the monotherapy arm.

It’s still a little bit early to say anything because it’s still a phase I study. So we really need to confirm the efficacy in a phase II study which is currently ongoing in a monotherapy sub-cutaneous fashion. If the drug can move on and prove to be really effective and safe this will open up a really new therapeutic avenue for patients with relapsed or refractory multiple myeloma. The drug appears to be tolerable even in older, frail patients, at least in our experience. The response appears to be durable so patients who respond early on continue to maintain the responses. It was good to see the handful of patients with prior BCMA CAR T failure were also able to salvage with this therapy. So I see this drug being used in the relapsed/refractory setting; hopefully, with future studies, we’ll be testing this in earlier lines of therapies.