Emma Searle, MD, University of Manchester, Manchester, United Kingdom, discusses findings from the MajesTEC-2 trial, evaluating teclistamab combined with subcutaneous datatumumab and lenalidomide in patients with multiple myeloma (MM).

These results were presented at the 2022 American Society of Hematology (ASH) Annual Meeting & Exposition in New Orleans, LA.

Transcript:

Hello, my name's Emma Searle. I'm a consultant hematologist based at the Christie Hospital in University of Manchester in England. It was my pleasure to have an abstract selected by the organizers to present the MajesTEC-2 data here at ASH 2022. I think this is the first of early data we're starting to get through in which the BCMA bispecifics are being considered as earlier lines of therapy and in combination for the management of patients with relapsed multiple myeloma.

In this cohort of MajesTEC-2, we looked at patients who'd received between 1 and 3 prior lines of therapy, and they were given teclistamab, daratumumab, and lenalidomide. There were 2 different teclistamab dosing schedules looked at, but the overall data showed a very high response rate of 94% with a [complete response] CR or better rate of 55% and a [very good partial response] VGPR or better rate of 90%—so, very exciting efficacy rates.

It's a bit too early really to comment on the durability of response because the median length of follow-up was just over 8 months. But at the point of data cutoff, over 80% of patients remained on treatment with an ongoing response. In terms of what we've learned about the safety signals from using these agents in combination, neutropenia is a very common event, and the use of [granulocyte colony-stimulating factor] G-CSF was encouraged during the study to help manage that. Febrile neutropenia, though, was much less common with only 4 patients out of the 32 treated in this cohort experiencing that side effect.

Cytokine release syndrome (CRS) was also a very common event, but it appears to be very manageable. All but 1 case occurred during cycle 1 with the majority of incidents of CRS occurring during step-up or first treatment dose. Tocilizumab use was frequent but encouraged by the protocol that wasn’t used prophylactically, and the CRS [in the main cohort] resolved rapidly with a median duration of 2 days. There were no grade 3 or 4 cytokine release syndrome events and no cases of [immune effector cell-associated neurotoxicity syndrome] ICANS, which I think is important for all of us as we think about our future practice with these agents.

In terms of non-hematological toxicity, a lot of it is low grade and very common with other treatment modalities that we have in myeloma, but I think the area of precaution is around infection. 90% of patients experienced an infection of some grades during the treatment with this regime, and around a third of patients experienced more serious infection—grade 3 or 4 infection. In the main [cohort], those were COVID-19, upper respiratory tract infections and pneumonia, and we did lose 2 patients from this cohort to infection, 1 from COVID-19, and 1 from multi-organ failure secondary to sepsis. There was an additional COVID patient who experienced COVID-19 that led to the cessation of therapy.

Moving forward, we all need to be vigilant in prophylaxing against those infections and managing them promptly. That's an important learning point from the data that we're seeing with both teclistamab and other BCMA-targeting immunotherapy modalities.

In conclusion, it’s exciting to see the response rates that can be achieved through combination therapy with teclistamab as an earlier line of therapy, but the important next step is comparison against standard-of care, and that is planned in the upcoming MajestTEC-7 trial, in which teclistamab, daratumumab, and lenalidomide will be compared to lenalidomide, daratumumab, and dexamthasome, so I’ll look forward to seeing the data emerging from that.

Source:

Searle E, Quach H, Wong S W, et al. Teclistamab in Combination with Subcutaneous Daratumumab and Lenalidomide in Patients with Multiple Myeloma: Results from One Cohort of MajesTEC-2, a Phase1b, Multicohort Study. Presented at the ASH Annual Meeting & Exposition; December 10-13, 2022; New Orleans, LA, and virtual. Abstract 160.