Abstract
Introduction: Teclistamab (tec) is the first globally approved B-cell maturation antigen (BCMA) × CD3 bispecific antibody (BsAb) with weight-based dosing. Tec demonstrated deep, and durable responses with a manageable safety profile in patients with triple-class exposed relapsed/refractory multiple myeloma (TCE RRMM) in MajesTEC-1. Here, we present data from a large cohort of Asian pts who received tec in trials and in a non-trial setting.
Methods: Two cohorts of Asian pts were evaluated: the Asian Trial cohort included 52 pts with RRMM from theMajesTEC-1 China cohort (NCT04557098) and MMY1002 Japan study (NCT04696809), and the Asian non-trial cohort included 47 pts from Korea and Singapore who received tec via a pre-approval access program. Enrolled pts received ≥3 prior lines of therapy (LOT), including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.Pts received tec at the RP2D (1.5 mg/kg subcutaneous once weekly [QW] preceded by step-up dosing with the option to switch to Q2W if response was maintained for ≥6 mo). The efficacy outcomes included overall response rate (ORR), complete response or better (≥CR), very good partial response or better (≥VGPR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety graded per CTCAE v4.03.
Results: In the Asian trial cohort (N=52), median age was 67 years (range 42−84), median weight was 58.0 kg [range, 37.5–86.4]), median prior LOT was 5 (range, 2–14), 38.5% had high-risk cytogenetics, and 25.0% had soft-tissue extramedullary disease (EMD), no pts had prior BCMA exposure. At 26.3 month (mo) median follow-up (FU), ORR (95% CI) was 76.9% (63.2–87.5), with 63.5% and 76.9% achieving ≥CR and ≥VGPR, respectively. Overall, 82.6% of responders achieved ≥CR. Twenty-eight pts (53.8%) switched from QW to Q2W (13 and 15 in China and Japan cohorts, respectively) with a median time to switch to Q2W of 9.3 mo (range: 7.1–26.0). Median DOR, PFS, and OS were not reached. The 24-mo DOR, PFS, and OS were 67.5%, 59.5%, and 71.4%, respectively. The ORR and ≥CR rates across subgroups were: triple-class refractory (n=33), 78.8%/60.6%; penta-drug refractory (n=9), 66.7%/55.6%; age ≥75 years (n=7), 85.7%/71.4%; ECOG PS ≥1 (n=28), 64.3%/50.0%; ISS-III (n=10), 60.0%/30%; high-risk cytogenetics (n=20), 60.0%/30%; and EMD (n=13), 46.2%/23.1%. For pts with ≥CR (n=33), 24-mo DOR, PFS, and OS trended longer at 81.8%, 81.8%, and 90.9%, respectively; medians were not reached. Pts who received ≤3 prior LOT (n=14) had higher ORR/≥CR rates (85.7%/85.7%), and higher 24-mo DOR, PFS and OS rates (91.7%, 78.6%, 85.7%, respectively).
The most frequent adverse events were cytokine release syndrome, cytopenias, and infections, which are consistent with the known profile of BCMA BsAbs. The incidence of new-onset grade ≥3 infections were more frequent within the first 6 mo of tec therapy and decreased over time: 32.7% (17/52) within first 6 mo, 26.3% (10/38) within >6 to 12 mo, 26.7% (8/30) within >12 to 18 mo, 14.8% (4/27) within >18 to 24 mo, and 10.5% (2/19) >24 mo. There was 1 discontinuation and 1 death due to infection. 46 pts (88.5%) had ≥1 postbaseline IgG level <400mg/dL after tec therapy; median time to IgG <400mg/dL was 1.3 mo (range 0.2–5.7), and 43 pts (82.7%) received ≥1 dose of Ig replacement (either IV or SC). Mean IgG level began to rise after 6 mo of tec therapy and remained consistently above 400 mg/dL after 8 mo.
In the non-trial cohort (N=47), 55.3% of pts were aged ≥65 yrs, 72.3% had ≥5 prior LOTs; 25.5% had high risk cytogenetics, and 19.1% had soft-tissue EMD. Many pts also had features that would have made them ineligible for MajesTEC-1 inclusion: 29.8% with ECOG 2-3, 12.8% with CrCl <30 mL/min, and 6.4% with prior BCMA exposure. Overall, 32 pts (68.1%) achieved a response, and 21 pts (44.7%) had ≥CR (serological), 16/32 pts (50.0%) remained in response at 12-mo.Conclusions: In this largest cohort of Asian pts treated with BCMA BsAb reported to date, tec consistently showed deep and durable responses in both trial and non-trial setting. The overall safety profile was consistent with the pivotal MajesTEC-1 study. A notable temporal decrease in the incidence of new onset high grade infections may reflect increased Ig use and a biweekly dosing interval. These findings support Tec's adoption as the new standard of care for patients with TCE RRMM and emphasize the importance of infection management including Ig use.
