Systematic review and meta-analysis of second primary malignant neoplasms after T-cell-engaging bispecific antibody therapy

T-cell-engaging bispecific antibodies (BsAbs) are increasingly used in B-cell non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). Understanding their safety profile is critical. Systematic review and meta-analysis of clinical trials and real-world studies of BsAbs in adults with NHL or MM evaluated the frequency of second primary malignancies (SPMs) after BsAbs therapy. Twenty studies (26 cohorts; 2551 patients) met inclusion criteria. Among 8 studies (10 cohorts; 1003 patients) reporting total SPMs, meta-analysis yielded a pooled estimated frequency of3.5% (95% CI 1.8-6.9) at a median follow-up of 17.5 months (range 5.7-25.6). Disease-specific estimates were 3.8% (95% CI 2.3-6.3) for NHL and 3.4% (0-76.7) for MM. Six studies (8 cohorts; 748 patients) reporting SPMs leading to treatment discontinuation showed a pooled estimate of 2.2% (95% CI 1.5-3.1). Nineteen studies (24 cohorts; 2330 patients) reporting SPMs leading to death yielded a pooled estimate of1.4% (95% CI 1.1-1.9). In exploratory analyses, no variables were associated with total SPM estimates. The authors conclude that SPMs are a clinically relevant complication of BsAbs therapy.