Teclistamab is the first approved B-cell maturation antigen × CD3 bispecific antibody (BsAb) for the treatment of triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM), with weight-based dosing and the longest study follow-up of any BsAb in MM. In the pivotal phase 1/2 MajesTEC-1 study (NCT03145181/NCT04557098), teclistamab demonstrated rapid, deep, and durable responses (overall response rate [ORR], 63.0%; complete response or better [≥CR] rate, 46.1%; median duration of response [mDOR], 24 mo) and a low rate of discontinuations due to adverse events (AEs; 4.8%). This subgroup analysis of MajesTEC-1 reports the overall safety and efficacy of RRMM patients (pts) who received 2-3 prior lines of therapy vs. pts with 4 or more prior lines of therapies, with extended follow-up of 30 months.

Pts received the recommended phase 2 dose (RP2D) of teclistamab (1.5 mg/kg QW) and could switch to Q2W dosing if in partial response or better after ≥4 cycles of therapy (phase 1) or in ≥CR for ≥6 mo (phase 2). The primary endpoint was ORR (assessed per IMWG 2016 criteria). AEs were graded per CTCAE v4.03. CRS and ICANS were graded per ASTCT. Safety was reported in the overall population and efficacy was evaluated in pts who received 2-3 prior lines of therapy (≤3 LoT) vs. pts who received more than 3 prior lines of therapies (> 3 LoT).

Of 165 pts who had received teclistamab as of Aug 2023, 26% (43/165) pts received ≤ 3 prior LoT and 74% (122/165) patients received > 3 prior LoT. Pts characteristics were similar between the groups, especially in terms of high-risk features. At 30.4 mo mFU, pts that received ≤3 prior LoT achieved an ORR of 74.4% with 60.5% of pts achieving ≥ CR [sCR 46.5% and CR 14%]. mPFS was 21.7 mo (95% CI, 13.8–NR), mDOR was 24.0 mo (95% CI, 14.0–NE) and median overall survival was not reached (95% CI, 18.3–NE). Pts who had > 3 prior LoT had an ORR of 59%, with 41% of pts achieving ≥CR [sCR 36.1% and CR 4.9%], mPFS was 9.7 mo (95% CI, 6.4–13.1), mDOR was 22.4 mo (95% CI, 14.9–NE) and median overall survival was 17.7 mo (95% CI, 12.2–29.7). In the overall population, hematologic AEs (any grade/grade 3/4) included neutropenia (72%/65%), anemia (55%/38%), thrombocytopenia (42%/23%), and lymphopenia (36%/35%). Infections occurred in 79% of pts (55% grade 3/4). Of grade 5 infections, 18/22 were due to COVID-19, reflecting study conduct during the COVID-19 pandemic. Onset of new grade ≥3 infections generally decreased over time, which aligned approximately with the median time of switch to Q2W dosing; other factors, such as increasing use of IVIG, may also contribute to this trend. AEs leading to dose reduction (n = 1) or discontinuation (n = 8; 5 due to infection) were infrequent. No new safety signals were reported.

With the longest follow-up of any BsAb in MM, teclistamab continues to demonstrate deep and durable responses, especially in the subgroup of less heavily treated patients (≤3 prior LoT), which demonstrates even better PFS and complete response rates results than those patients in later lines of treatment (> 3 prior LOT). The safety profile of teclistamab remains consistent with that of BCMA-targeted bispecific therapies, with an important decrease in new onset of severe infections with time.

This study was funded by Johnson & Johnson Innovative Medicine.