Teclistamab Efficacy Following Prior BCMA-Directed Therapy in RRMM

A multicenter US study investigated the outcomes of teclistamab-cqyv (Tecvayli), a BCMA-directed bispecific antibody, in patients with relapsed/refractory multiple myeloma who had prior exposure to BCMA-directed therapy. While teclistamab is approved for RRMM after ≥4 prior lines of therapy, the pivotal MajesTEC-1 trial (NCT04557098) excluded patients with prior BCMA-directed therapy. This retrospective analysis of 385 patients, 193 of whom received prior BCMA-directed therapy, provides crucial real-world data on this increasingly common clinical scenario.

The study revealed that patients with prior BCMA-directed therapy had a numerically lower overall response rate (ORR) to teclistamab (51.4%) compared with those without prior BCMA-directed therapy (61.5%). There was also a trend towards worse progression-free survival (PFS) in the prior BCMA-directed therapy group (median 4.6 vs 8.2 months). Notably, multivariable analysis did not find prior BCMA-directed therapy to be independently associated with PFS.

Interestingly, the time interval between the last BCMA-directed therapy exposure and teclistamab initiation appeared to impact outcomes. Patients with a longer interval (>8.7 months) demonstrated a superior median PFS with teclistamab (8.1 months) compared with those with a shorter interval (<8.7 months; 2.5 months).

“What we found was that those patients had a slightly lower response rate, so 51% vs 61% which is what we usually see in patients who did not receive BCMA-directed therapy before teclistamab. So it was slightly lower,” explains Jack Khouri, MD, assistant professor at Cleveland Clinic Lerner College of Medicine and Case Western Reserve University, in an interview with Targeted Oncology^TM.

“Then there was a trend towards a worse progression-free survival when patients had received BCMA-directed therapies before the teclistamab. This is really important to know, and this is kind of similar to what we've seen in clinical trials that looked at prior BCMA-directed therapies on the response to teclistamab.”

The toxicity profile of teclistamab in BCMA-exposed patients was generally similar to that observed in BCMA-naïve patients, with comparable rates of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome.

“The main message from the abstract [is that] we are always looking into tips on how to sequence these therapies in the real-world and and knowing that, I think, is really going to inform our practice.”