Background: Teclistamab is the first approved off-the-shelf BCMA×CD3 bispecific antibody 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. Here, we present updated results with extended follow-up of ~2 y (22 mo). Methods: 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. Pts received teclistamab 1.5 mg/kg QW (the recommended phase 2 dose [RP2D]), with the option to switch to Q2W dosing if they achieved ≥partial response after ≥4 cycles of therapy in phase 1 or ≥CR for ≥6 months in phase 2. The primary endpoint was ORR (assessed per IMWG 2016 criteria by computerized algorithm). AEs were graded per CTCAE v4.03. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT guidelines. Results: As of Dec 9, 2022, 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): 92% daratumumab exposed; 78% triple-class refractory; 81% daratumumab-refractory; and 90% refractory to last LOT. At 22 mo mFU, 43% of pts achieved ≥CR, mDOR was 24 mo (95% CI, 16.2–not estimable [NE]), mDOR in pts achieving ≥CR was not reached (95% CI, 24.0–NE), mPFS was 12.5 mo (95% CI, 8.8–17.2), and median overall survival was 21.9 mo (95% CI, 16.0–NE). Hematologic AEs (any grade [gr]/gr 3/4) included neutropenia (72%/65%), anemia (54%/38%), thrombocytopenia (42%/22%), and lymphopenia (35%/33%). Infections occurred in 78% of pts (52% gr 3/4); key infections included respiratory (56%), COVID-19 (27%), other viral (10%), GI (8%), fungal (5%), 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. 6 treatment-related deaths have occurred (3 due to COVID-19). Of the 49 pts who remain on study, ~90% have received Q2W dosing. Conclusions: After ~2 y mFU, pts receiving teclistamab demonstrated deep and durable responses regardless of refractory status, with mPFS of 12.5 mo and mDOR of 24 mo (not reached in those achieving ≥CR). These long-term follow-up data support teclistamab as a safe and effective off-the-shelf BCMA bispecific therapy for pts with RRMM. Clinical trial information: NCT03145181, NCT04557098.