Teclistamab Demonstrates Durable Response Rates in BCMA-Pretreated Multiple Myeloma

Teclistamab (Tecvayli) displayed deep and durable responses with a manageable safety profile in patients with prior exposure to BCMA-targeted agents, according to Saad Z. Usmani, MD, MBA, FACP. He added that these results suggest that this population can benefit from serial targeting of BCMA.

The phase 1/2 MajesTEC-1 trial (NCT04557098) is an open-label, multicohort study investigating teclistamab, a T-cell redirecting bispecific antibody that targets BCMA and CD3 receptors, in patients with relapsed/refractory multiple myeloma who have received at least 3 prior lines of therapy. Findings from an efficacy and safety analysis of cohort C of this trial, which included patients with prior BCMA-directed exposure, were presented at the 2022 EHA Congress.¹

In cohort C, among 40 patients with prior exposure to either antibody-drug conjugates (ADCs) or CAR T-cell therapy, the overall response rate (ORR) with teclistamab was 52.5% (n = 21; 95% CI, 36.1%-68.5%). Among 29 patients with prior ADC exposure, the ORR was 55.2%. The ORR was 53.3% among the 15 patients with prior CAR T-cell therapy exposure. Additionally, 3 of the 4 patients who had been exposed to both CAR T-cell therapy and ADCs responded.

At the data analysis cutoff date of March 16, 2022, the median duration of response (DOR) was not reached (95% CI, 10.5 months-not evaluable). Additionally, at a median follow-up of 11.8 months (range, 3.6-13.8 months), 71.4% of responders maintained their response.

“Patients who have had prior BCMA, ADC, or CAR T-cell therapy targeting BCMA can benefit from a BCMA-directed bispecific antibody,” Usmani said.

In an interview with OncLive^®, Usmani, chief of the Myeloma Service at Memorial Sloan Kettering Cancer Center, discussed key efficacy findings that support the use of teclistamab in this population. In addition, he raised considerations for next steps in the patients who did not respond to this agent.

OncLive^®: Of all the cohorts studied in the MajesTEC-1 trial, what were you looking for in the patient population for this analysis?

Usmani: Cohort C was specifically designed to enroll patients who had relapsed/refractory myeloma. Patients had to have prior proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody exposure and/or refractoriness, along with prior BCMA-directed therapy, as this was a BCMA-exposed patient population.

What were some of the key efficacy findings that were presented at EHA?

The primary end point for this study was ORR. Secondary end points included DOR, very good partial response or better, and complete response or better. A total of 40 patients were enrolled, and all patients were triple-class exposed, with 85% being triple-class refractory and 85% being refractory to the last line of treatment. Of the 40 patients, 29 had prior treatment with ADCs targeting BCMA, and 15 had prior BCMA-directed CAR T-cell therapy. A total of 4 patients had both.

In the patients who had prior ADC exposure, the ORR was 55.2%. In prior CAR T-cell therapy–exposed patients, the ORR was 53.3%. In the whole cohort of 40 patients, the ORR was 52.5%. These were good results that we were not expecting and were pleasantly surprised with. We saw high response rates with what looks like good durability.

How did safety data compare with that of other cohorts?

Safety [in this cohort] was similar to that in the other MajesTEC-1 cohorts. In terms of cytokine release syndrome management, low neurotoxicity signals were seen.

What do these responses show about potential treatment sequencing strategies in this population?

[These data] help us get some hypotheses around sequencing of treatment. Now that we know the effectiveness of using a bispecific antibody targeting BCMA after a patient has had a BCMA-directed CAR T-cell therapy and progressed on it, it’s [an option] we can certainly consider.

What are the next steps for research in this arena?

We are looking at the long-term follow-up data in these patients to see if they get the same kind of progression-free survival benefit compared with the non–BCMA exposed patients. More importantly, considering those who did not respond, which was a little under half of the patients, [we are asking:] What were the reasons for that? Was it a T-cell health issue that prevented those patients from responding? Was it disease biology? There are more questions that we can ask about the patients who did not respond.

Reference

Touzeau C, Krishnan AY, Moreau P, et al. Evaluating teclistamab in patients with relapsed/refractory multiple myeloma following exposure to other B-cell maturation antigen (BCMA)–targeted agents. Presented at: 2022 EHA Congress; June 9-12, 2022; Vienna, Austria. Abstract S184.