Phase 2 teclistamab BCMA×CD3 T‑cell–redirecting bispecific antibody in R/R Waldenström’s macroglobulinemia.

This single-group, open-label Phase 2 study evaluates teclistamab (a BCMA×CD3 bispecific monoclonal antibody that redirects T cells to kill BCMA-expressing malignant B-lineage cells) in relapsed or refractory Waldenström’s macroglobulinemia after prior therapy, with outcomes including efficacy plus safety/tolerability and depth/speed of response. Participants receive subcutaneous step-up dosing on days 1, 4, and 7 of the first 14-day cycle, then weekly dosing for cycles 2–5 (28-day cycles) and less frequent dosing for cycles 6–9 (56-day cycles), for up to 9 cycles total, with follow-up up to 3 years after last dose. The study also explores whether response differs by MYD88 and CXCR4 mutation combinations—clinically relevant because MYD88 is very common in WM (90%+) and CXCR4 mutations occur in a meaningful subset (30–40%), and both can influence biology and drug sensitivity. The drug is developed by Janssen (Johnson & Johnson), while Massachusetts General Hospital is leading this investigator-sponsored trial. Today’s care for R/R WM typically relies on BTK inhibitors (ibrutinib, zanubrutinib, acalabrutinib), rituximab-based chemoimmunotherapy (e.g., bendamustine-rituximab), proteasome inhibitor–based regimens, and clinical trials; this program tests whether BCMA-directed T-cell redirection—proven in multiple myeloma—can translate into meaningful activity in WM.