Teclistamab in Relapsed Refractory Multiple Myeloma: Multi-Institutional Real-World Study

Introduction: Teclistamab is the first BCMA-targeting bispecific antibody (bsAb) that has received FDA approval in RRMM based on the MajesTEC-1 study, which showed a single-agent ORR of 63%. In this report, we present the safety and efficacy of teclistamab since its approval in a real-world multi-institutional cohort.

Methods: All consecutive patients with RRMM treated with at least one dose of standard-of-care teclistamab at 5 academic centers in the US were included in this study. Data including patient demographics, disease, and treatment characteristics at the most recent assessment before starting treatment were retrospectively collected.

Results: A total of 89 patients were treated across 5 academic institutions. The median age was 68 years (range: 37-89), with 48% (n=43) females. Among the patients, 30% (n=27) were Black, 2.2% (n=2) Asian and 12% (n=11) were other minorities. High-risk cytogenetic profile was observed in 65% (n=49/75) of the patients. About 48% (n=39) of the patients exhibited EMD on PET-CT. Four patients had CNS involvement, 1 had pPCL, and 3 had concomitant AL amyloidosis. Furthermore, 98% (n=87) of the patients had triple-class refractory MM, while 85% (n=76) had penta-refractory MM. The median prior lines of therapy were 6 ( range: 3-13) and 80% (n=71) of patients received a prior ASCT. About 37% (n=33) had received prior BCMA-directed therapy, which included BCMA CAR-T in 17, BCMA BsAb in 5, and Belantamab mafadotin in 11 patients . Table 1 compares this patient cohort with the MajesTEC-1 study population. Grade 1/2 CRS was observed in 48% (n=43) of patients, while 3% (n=3) experienced grade 4 CRS. Grade 1/2 ICANS was noted in 7% (n=6) of patients, grade 3/4 in 4.4% (n=4), and grade 5 in 1 patient. Steroids were utilized in 22% (n=16) of patients, while tocilizumab was administered in 44% (n=32) of patients. Notably, step-up dosing of teclistamab was administered entirely in the outpatient setting in 9% (n=8) of patients. For the remaining, inpatient step-up dosing was administered, and the median hospitalization duration was 10 days. At a median follow-up of 1.35 months (range: 0.16-4.38), the ORR among the evaluable patients was 55%, with rates of ≥ VGPR and PR at 37% (n=28) and 18% (n=13), respectively. The 3-month PFS rate was 54% (95% CI: 43%, 69%), while the 3-month OS rate was 80% (95% CI: 71%, 90%). Multivariate analysis did not reveal any significant associations between disease response and the following factors: number of prior lines of therapy (HR 1.03, 95% CI 0.76-1.42), baseline lymphocyte counts (HR 0.98, 95% CI 0.47-2.02), high-risk cytogenetics (HR 0.38, 95% CI 0.09-1.39) and the presence of extramedullary disease (HR 0.56, 95% CI 0.15-1.93). There was a trend towards worse ORR in patients with prior exposure to BCMA targeting agents, albeit not quite significant (HR 0.28, 95% CI 0.07-1.04, p=0.065). There were 61 infectious events with 50%, 45% and 5% of these being viral, bacterial, and fungal infections, respectively. The most common sources of infections were upper respiratory tract infections/pneumonias (33%), blood borne infections including bacteremia and viremia (27%) and urinary tract infections (11%). The cumulative incidence of any infection at 3 months was 55% and grade 3/4 infections were seen in 55% (n= 54) of cases. There was one grade 5 infection noted in this study due to COVID 19 pneumonia. Primary IVIG and PJP prophylaxis were used in 40% (n=34) and 51% (n=43) of patients, respectively and the use of such was associated with a significant reduction of infectious events (26/51 [51%] of any infectious event for no IVIG use vs 13/34 [38%] for IVIG use, p= 0.015). The results will be updated with longer follow-up at the meeting.

Conclusion : In this large real-world, multi-institutional study including a diverse cohort of heavily pretreated patients with triple-class and penta-refractory MM, including approximately 40% with prior BCMA exposure, teclistamab demonstrated a respectable ORR of 55% with ≥ VGPR in 37% of cases. The incidence of Grade 3 or higher infections at 3 months remained high at 56%, however the use of prophylactic measures, including primary IVIG prophylaxis was associated with a significant reduction of all infections and should be strongly considered in patients receiving teclistamab.