At the 2023 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, Illinois, Niels W.C.J. van de Donk, MD, PhD, presented results from the 2-year follow-up of the MajesTEC-1 trial, which indicated that BCMA-CD3 bispecific antibody teclistamab demonstrated durable responses for heavily pre-treated patients with relapsed/refractory (R/R) multiple myeloma (MM). 

Transcript: 

Hello, my name is Niels van de Donk. I'm a professor of hematology at Amsterdam University Medical Center in Amsterdam, the Netherlands. At ASCO I will present the results from [the] MajesTEC-1 study with a longer follow-up now of approximately 2 years. 

In the MajesTEC-1 study, we evaluated the safety profile and efficacy of teclistamab in heavily pretreated multiple myeloma patients. When the study was starting, we needed new drugs for the population of patients that [were] exposed to CD38 antibody, to [immunomodulatory imide drug (IMiD), and to [proteasome inhibitors] (PI), because these patients have a very poor outcome. They have a response of only 30%, a median progression-free survival of only 3 months, and a median overall survival of only 12 months. We needed new drugs with novel modes of action for this unmet medical need population.

At this moment, we have treated 165 patients with heavily pretreated multiple myeloma, all triple-class exposed, and 75% being triple-class refractory with teclistamab at the recommended phase 2 dose. Now with a longer follow-up of 2 years, we see a 65% response rate, and with longer follow-up, we also see that the percentage of patients with a deep remission, with a complete response, is increasing towards 45%. This is of course much higher than what you may expect from other therapies in this segment of patients.

With longer follow-up, we also see that the median duration of response has increased to 22 months for all the patients with [a] response and to 27 months for the patients that have achieved complete remission. With 2 years follow-up, median progression-free survival remains stable at 11 months, and it was 27 months for those who achieved complete remission. We also have now more mature data on overall survival. For the whole group of patients, [the] median overall survival was 22 months. This is almost double what we typically saw in this segment of patients when they were treated with a physician's choice of therapy outside of a clinical trial.

For the patients [who] had achieved complete remission, median overall survival was not yet reached. The safety profile remained similar to what has been reported before. We see cytokine release syndrome in approximately 70% of the patients, especially during step-up dosing and the first full dose. This can be managed well with tocilizumab or sometimes steroids. We also see cytopenias in these patients, especially during cycles 1 and 2, probably related to the cytokines that are produced in the bone marrow when the myeloma cells are eliminated by the T-cells. These cytokines can also suppress normal hematopoiesis. What we see increase is the percentage of infections, and there's also an increase in severe infections [of] grade 3 or higher.

The good thing is that we now have a better understanding of how to manage these infections in patients treated with teclistamab. We need to give our patients prophylactic antibiotics like cotrimoxazole. We have to give them a herpes simplex virus prophylaxis to prevent against herpes zoster and herpes simplex infections. I think what is also very important is to give [intravenous immunoglobulin] IVIG supplementation treatment when IgG levels drop below 4 grams per liter.

The increase in infections is, in fact, reducing over time. This may be related to the fact that an increasing number of patients [are] now getting teclistamab every 2 weeks or every 4 weeks in the trial while they started with every week dosing. Probably less intensive sort of maintenance strategy is also important when it comes to infectious risk. This data is very important and led last year to the approval of teclistamab in Europe and in the United States so that we now can treat also outside of a clinical trial these triple-class refractory patients with teclistamab, which is important because again, the results in this patient population were very poor.

These patients now have access to a novel BCMA-targeting drug. Because of the efficacy of this drug in heavily pretreated myeloma, we are now also trying to bring this agent to early lines of therapy. We had the MajesTEC-3 trial in early relapse refractory multiple myeloma, where it was combined with daratumumab and compared with [the] standard-of-care. We will learn about this study in the nearby future. 

We have an ongoing study in patients that have been transplanted where we evaluate teclistamab either as monotherapy or in combination with lenalidomide and compare it with the standard-of-care maintenance drug lenalidomide. We hope to give also transplant-eligible patients teclistamab as part of first-line therapy to probably have in the future a more effective maintenance strategy. So, more to come in the nearby future.

Source: 

van de Donk, N, Moreau, P, Garfall A, et al. Long-term follow-up from MajesTEC-1 of teclistamab, a B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM). Presented at the ASCO Annual Meeting; June 2-6, 2023; Chicago, Illinois. Abstract 220069