Updates in Newly Diagnosed and Relapsed/Refractory Multiple Myeloma from ASH 2021 - Episode 2

A Role for Bispecific Antibodies in R/R MM: Data From MonumenTAL-1 and MajesTEC-1 Studies

Insight on results from the MonumenTAL-1 and MajesTEC-1 studies, which evaluated bispecific antibodies in patients with relapsed/refractory multiple myeloma.


Amrita Y. Krishnan, MD: ASH [American Society of Hematology Annual Meeting] 2021 was exciting for the myeloma field because of data with bispecific antibodies. There were multiple different bispecific antibodies presented at ASH. One was the MonumenTAL-1 study that I presented, which used a bispecific antibody targeting GPRC5D, a receptor that’s highly expressed in myeloma cells. In this study with patients with relapsed/refractory myeloma who had a median of 5 to 6 prior lines of therapy, including 80% of them being penta-drug exposed, we saw response rates of 67% to 70%; that was very encouraging. Over 50% of the patients had a vgPR [very good partial response] or better.

The adverse-effect profile showed that the majority of patients, 77%, had cytokine release but mostly mild. Some of the unique adverse effects with talquetamab were in terms of its target on keratinized tissue, so we did see nail toxicity and some skin rashes in up to 70% of patients. We also saw dysgeusia in about 60% of patients. The encouraging thing about the drug was that patients seemed to get durable and deep responses, and many patients are still on treatment in both the weekly and biweekly dosing cohorts.

The other bispecific that was also very exciting was the teclistamab, a bispecific targeting BCMA. Teclistamab is in a more crowded space because there are multiple BCMA-targeting bispecific antibodies and, as many people know, also BCMA-targeting CAR [chimeric antigen receptor] T cells. Nonetheless, teclistamab in the MajesTEC-1 study showed very promising results in patients with advanced myeloma. We had about 70% of patients penta-drug exposed, and 30% were penta-drug refractory. They saw an overall response rate of 62%, with 58% of the patients getting a vgPR or better. Overall, the drug did seem to be well tolerated. There was a signal of infections in about a third of patients, so that certainly bears watching.

Teclistamab seemed to show durable and deep responses, and 1 question with bispecifics has always been the durability of response. Teclistamab did present some early progression-free survival [PFS] data. The 6-month PFS was 64%, the 9-month PFS was 58.5%, and the median overall survival has not been reached. It seems quite encouraging in terms of the durability of these responses.

Transcript edited for clarity.