In a meta-analysis reported in JAMA Oncology, Tomasik et al found that second primary malignant neoplasms were a “clinically relevant complication” of treatment with T-cell–engaging bispecific antibodies (BsAbs) in patients with non-Hodgkin lymphoma or multiple myeloma.
Study Details
The analysis involved data from clinical trials and real-world studies in non-Hodgkin lymphoma and multiple myeloma reported through October 1, 2025, that included second primary malignant neoplasm outcomes.
Key Findings
A total of 20 studies, including 26 cohorts and a total of 2,551 patients, met inclusion criteria for the analysis.
Among eight studies (10 cohorts, 1,003 patients) reporting total second primary malignancies, the second primary malignancy rate was 3.5% (95% confidence interval [CI] = 1.8%–6.9%) at a median follow-up of 17.4 months (range = 5.7–25.6 months); rates were 3.8% (95% CI = 2.3%–6.3%) among patients with non-Hodgkin lymphoma and 3.4% (95% CI = 0%–76.7%) among those with multiple myeloma. In an analysis including prespecified study-level covariates (such as follow-up duration, disease category, prior therapy courses, and age), no variables were significantly associated with total second primary malignancy estimates. Second primary malignancies identified included nonmelanoma skin cancers (n = 9) and hematologic malignant neoplasms (n = 7), including myelodysplastic syndromes (n = 4) and acute myeloid leukemias (n = 2); remaining cases consisted of heterogeneous solid tumors with no predominant subtype.
Among six studies (8 cohorts, 748 patients) reporting second primary malignancies leading to treatment discontinuation, the discontinuation rate was 2.2% (95% CI = 1.5%–3.1%). Among 19 studies (24 cohorts, 2,330 patients) reporting second primary malignancies leading to death, the death rate was 1.4% (95% CI = 1.1%–1.9%).
The investigators concluded: “In this systematic review and meta-analysis, despite relatively short follow-up, second primary malignancies were a measurable and clinically relevant complication of BsAb therapy. Heterogeneous and inconsistent reporting currently complicates their comprehensive assessment, highlighting the need for standardized long-term safety surveillance in clinical trials examining BsAbs.”
Roni Shouval, MD, PhD, of the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, is the corresponding author for the JAMA Oncology article.
DISCLOSURE: The study was supported by the U.S. National Cancer Institute and others. For full disclosures of the study authors, visit jamanetwork.com.
