The triple combination of teclistamab plus daratumumab and lenalidomide had an acceptable side effect profile and showed early efficacy among transplant-eligible patients with newly diagnosed multiple myeloma (NDMM) who do not receive a transplant because of a patient or physician’s choice, as well as those who are ineligible for or not intended for autologous hematopoietic cell transplantation (AHCT). These preliminary results of the phase III MajesTEC-7 trial’s safety run-in cohort 1 were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.1
The rationale for combining teclistamab with daratumumab and lenalidomide is based on the hypothesis that this will lead to a synergistic effect on myeloma cells after observing the positive results from this triple combination in the phase Ib MajesTEC-2 study in patients with relapsed or refractory MM, according to presenting author Cyrille Touzeau, MD, PhD, of the University Hospital of Nantes in France.
While the standard of care for patients with NDMM who are not eligible for transplant is the combination of daratumumab, lenalidomide, and dexamethasone (DRd), based on the MAIA phase III trial,2 this combination eventually leads to relapse for most patients, highlighting that additional, more effective frontline therapy options are needed.
“The most important result of the study is that the combination of teclistamab, daratumumab, and lenalidomide (tec-DR) in the safety run-in, non-randomized cohort 1 of the study showed substantial efficacy in patients with NDMM who were transplant ineligible or not intended for transplant,” Dr. Touzeau told ASH Clinical News.
Patients in cohort 1 of the MajesTEC-7 trial were a median age of 72.5 years, and 17 of the 26 patients (65.4%) were male. A total of 21 patients were white (80.8%), 22 (84.6%) were transplant ineligible, and 16 of the patients (61.5%) were fit according to the International Myeloma Working Group fragility score.
Patients received step-up dosing of teclistamab and daratumumab in cycle 1 and introduction of lenalidomide in cycle 2. They received the triple combination every two weeks in cycles 3 to 6 and every four weeks in cycle 7 and beyond. At the time of the clinical cutoff, patients had received a median of 15 cycles of therapy.
Among the 26 patients recruited to cohort 1, 92.3% of the patients achieved a very good partial response or better, and 80.8% of the patients achieved a complete response. At the time of the data cutoff with a median follow-up of 13.8 months, no patient who had achieved a response had progressed. The median time to first response was 1.0 month (range = 0.9-4.6 months), and the median time to best response was 6.5 months (range = 1.0-12.1 months). At the median follow-up, one progression-free survival (PFS) had occurred.
The estimated duration of response and PFS at 12 months is 100% and 96.2%, respectively.
“The [triple] combination had a manageable safety profile with low rates of treatment discontinuations due to treatment-emergent adverse events,” Dr. Touzeau said.
Cytokine release syndrome occurred in 61.5% of patients, mostly in cycle 1; all but one event were grade 1. One case of grade 1 immune effector cell-associated neurotoxicity syndrome occurred in one patient in cycle 1 and resolved. All patients experienced an infection (100%), the most frequent of which was COVID-19 in eight patients (30.8%), followed by bronchitis in seven patients (26.9%) and an upper respiratory tract infection, also in seven patients (26.9%). One death from influenza pneumonia occurred in a patient in cycle 3. Hypogammaglobulinemia occurred in 21 patients (80.8%).
Eight of the 26 patients (30.8%) had a grade 3-4 infection, most of which had an initial onset within the first three months. The authors concluded that the cumulative exposure to the triple combination over time has low impact on the incidence of grade 3-4 infections. Based on the experience of the program, the study authors also recommended that IVIg supplementation and infection prophylaxis should be initiated early and maintained throughout the course of treatment.
Going forward, Dr. Touzeau explained that “the randomized part of the MajesTEC-7 study has started, with lenalidomide initiated in cycle 2, as informed by the safety run-ins and the totality of data to date.” The randomized portion of the trial will compare teclistamab plus lenalidomide and daratumumab, and talquetamab plus lenalidomide plus daratumumab, each to the standard-of-care combination of DRd in 1,500 patients with NDMM.
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
- Touzeau C., Beksac M., Terpos, E. et al. Safety results from the phase 3 MajesTEC-7 study in patients (pts) with transplant ineligible/not intended newly diagnosed multiple myeloma (NDMM). Abstract 7506. Presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting; June 3, 2024; Chicago, Illinois.
- Facon T, Kumar SK, Plesner T, et al. Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(11):1582-1596.
