Therapeutic Strategies in Myeloma

CE / CME

Therapeutic Strategies in Multiple Myeloma: Overview of Current and Emerging Treatment Options

Pharmacists: 1.00 contact hour (0.1 CEUs)

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit

Nurses: 1.00 Nursing contact hour

Released: April 26, 2023

Expiration: April 25, 2024

Shaji K. Kumar
Shaji K. Kumar, MD

Activity

Progress
1
Course Completed

Overview of BCMA-Targeting Bispecific Antibodies in R/R MM

The BCMA targeted therapies continue to evolve. There are multiple different bispecific antibodies in clinical trials with different doses, schedules, and toxicity profiles. Hopefully as these drugs get approved, we will have more choices for treating patients with R/R disease.110,125-127

MagnetisMM-1: Phase I Study of Elranatamab for R/R MM After Established Therapy

The MagnetisMM trial looked at elranatamab, which is again a BCMA targeted bispecific antibody. The response rate was 64% in a heavily pretreated patient population.125,128

LINKER-MM1: Linvoseltamab (REGN5458) in R/R MM

The LINKER-MM1 trial was a first-in-human, open-label phase I/II study with step-up dosing followed by weekly, then every 2-week infusions in patients with MM who were R/R to ≥3 lines of prior therapy. Part 1 of the study involved linvoseltamab IV dose escalation. The primary objectives were safety, tolerability, dose-limiting toxicities, and RP2D. The secondary objectives were ORR, DoR, PFS, MRD status, and OS.129

Linvoseltamab in R/R MM: Responses

Linvoseltamab showed similar response rates of approximately 60% to 70% in this heavily pretreated patient population.130

Phase I Trial of ABBV-383, a BCMA-CD3 Bispecific Antibody

And finally, we have ABBV383, a third BCMA targeted bispecific antibody, which is convenient since it is administered once every 3 weeks. This agent has also shown very good activity in the relapsed setting.131

TRIMM-2: Phase IB Study of SC Teclistamab + Daratumumab in R/R MM

There are ongoing trials evaluating whether these bispecific antibodies can be combined with standard-of-care agents. We saw some early data with teclistamab in combination with daratumumab, again showing high response rates, including those patients who are refractory to anti CD38 monoclonal antibodies.132

The TRIMM 2 trial was a phase IB study of SC teclistamab plus daratumumab. A limited number of patients have been treated with this combination thus far.132

TRIMM-2: Response With Teclistamab + Daratumumab in R/R MM

The results appear to be quite promising and hopefully the larger cohort data will confirm these findings. Responses were durable and deepened over time. At median follow-up of 8.6 months, 66.7% of responders were alive and continuing on treatment.132

UNIVERSAL: Allogeneic CAR T-Cell Therapy With Anti-BCMA ALLO-715 in Patients With R/R MM

One of the greatest challenges that we encounter with the use of autologous CAR T cell therapy is the need to wait for CAR T cell manufacturing, so there has been significant interest in trying to use off-the-shelf allogeneic CAR T cells in patients with all hematologic malignancies, particularly MM. The UNIVERSAL trial was a multicenter, open-label, dose-escalation phase I study evaluating the anti-BCMA therapy ALLO-715 in patients with R/R MM, with the primary endpoints of safety and tolerability.133-135

UNVERSAL: Updated Phase I Safety and Efficacy Results From Dose Level 3

Limited data from the UNIVERSAL trial has shown that we can see good responses using these allogeneic CAR T cells, but more data are needed before we see how this therapy would fare in contrast to the autologous CAR T cell therapies.135

Which of the following investigational bispecific antibodies targeting BCMA could be an option on clinical trial for patients who are refractory to an IMiD, PI, and anti-CD38 mAb?