Emma Searle, PhD, discusses the dosing approach of the MajestTEC-2 trial (NCT04722146) and sequencing teclistamab (Tecvayli) in patients with multiple myeloma.
Emma Searle, MBChB, PhD, MA, MRCP, FRCPath, consultant hematologist at the Christie Hospital NHS Foundation Trust, and honorary senior lecturer at the University of Manchester, discusses the dosing approach of the MajestTEC-2 trial (NCT04722146) and sequencing teclistamab (Tecvayli) in patients with multiple myeloma.
The phase 1b trial had multiple cohorts in order to investigate the combination of teclistamab with other agents. In cohort E, it was given weekly in combination with daratumumab (Darzalex) and lenalidomide (Revlimid) and showed favorable efficacy and tolerability. Searle says that in other cohorts, investigators increasingly moved to longer dosing intervals for teclistamab when using it with other combinations such as daratumumab, lenalidomide, and bortezomib (Velcade) or daratumumab plus pomalidomide (Pomalyst). Because of the safety issues caused by using multi-agent regimens, longer dosing intervals may be helpful in improving tolerability.
According to Searle, trials have yet to determine the best line of therapy to use teclistamab. It is currently approved for patients who have received 4 prior lines of therapy, whereas MajesTEC-2 is investigating it in patients who had 1 to 3 prior lines. She notes that though oncologists try to use the most powerful agents earlier when patients can benefit most, it is unknown whether moving it earlier will be the best usage. Teclistamab will be investigated as part of a frontline regimen in transplant-ineligible patients in combination with daratumumab and lenalidomide in the phase 3 MajesTEC-7 trial (NCT05552222).
0:08 | I still think we've got a lot to learn about immunotherapy. We don't know how long we should be treating for. We don't know [if] we need to maintain the same dosing intensity. In the MajesTEC-2 trial, increasingly, we moved to longer dosing intervals. In this cohort, we moved to weekly dosing, but actually, in other cohorts in this study, there were longer dosing intervals. We do need to understand more about how to keep patients safe on these treatments. And we need to understand more about what line of therapy to use them at. Intuitively, we always think that we should use our most efficacious agents as early as possible. But we don't have the data yet to tell us where and when to use them. So [there is] lots of research to be done.