Teclistamab is the first approved off-the-shelf BCMA×CD3 bispecific antibody, with personalized weight based dosing, for the treatment of patients (pts) with RRMM based on data from the pivotal phase 1/2 MajesTEC-1 study (NCT03145181/NCT04557098). Moreau et al (NEJM 2022) reported rapid, deep, and durable responses: overall response rate (ORR) was 63% (39% ≥ complete response [CR] rate), with a median duration of response (mDOR) of 18.4 mo, and median progression-free survival (mPFS) of 11.3 mo after a median follow-up (mFU) of 14.1 mo. This subgroup analysis of MajesTEC-1 reports the overall safety and efficacy of RRMM patients who received 2-3 prior lines of therapy vs. patients with 4 or more prior lines of therapies, with extended follow-up of 23 months.

Eligible pts were aged ≥18 y, had documented MM (per IMWG 2016 criteria), and had received ≥3 prior lines of therapy (LOT), including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody. Prior BCMA-targeted therapy was not allowed in this cohort. The primary endpoint was ORR (assessed per IMWG 2016 criteria by independent review committee). AEs were graded per CTCAE v4.03. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT guidelines. Safety was reported in the overall population and efficacy was evaluated in patients who received 2-3 prior lines of therapy (≤3 LoT) vs. patients who received more than 3 prior lines of therapies (>3 LoT).

As of Jan 4, 2023, 165 pts had received teclistamab at the RP2D (median age, 64 y; 58% male; 26% high-risk cytogenetics; 12% International Staging System stage III). Pts had a median of 5 prior LOT (range, 2–14). 43 patients received ≤3 prior LoT and 122 patients received >3 prior LoT. In patients with ≤3 and >3 prior LOT; 58.1% vs. 84.4% pts were TCR and 46.5% vs. 78.7% pts were penta-drug exposed respectively. At 23 mo mFU, patients with ≤3 and >3 prior LOT achieved an ORR of 74.4% with 58.1% of patients achieving ≥CR vs. 59% with 41% of pts achieving ≥CR; the mPFS was 18.1 mo (95% CI, 13.8–26.9) vs. 9.7 mo (95% CI, 6.4–13.1), and the mOS was 25.9mo (95% CI, 18.3–NE) vs. 17.7 mo (95% CI, 12.2–NE), respectively. In the overall population, Hematologic AEs (any grade [gr]/gr 3/4) included neutropenia (72%/65%), anemia (55%/38%), thrombocytopenia (42%/22%), and lymphopenia (36%/35%). Infections occurred in 80% of pts (55% gr 3/4); key infections included respiratory (58%), COVID-19 (29%), other key viral (12%), GI (9%), fungal (6%), PJP (4%), and hepatitis B (0.6%). CRS occurred in 72% of pts (0.6% gr 3; no gr 4/5); 5 (3%) pts reported 9 ICANS events (all gr 1/2; all resolved). 1 pt in phase 1 required a teclistamab dose reduction due to neutropenia. 7 treatment-related deaths have occurred (4 due to COVID-19). Of the 47 pts who remain on study, ̃90% have received Q2W dosing.

With a 23 mFU, these data support teclistamab as a safe and effective therapeutic option for RRMM patients. The subgroup of less heavily treated patients (≤3 prior LoT) demonstrates even better PFS and complete response rate results than those patients in later lines of treatment (>3 prior LOT).

The development of this study was funded by Janssen Research & Development.