Second Primary Malignancies Emerge as Clinically Relevant Complication of T-Cell–Engaging Bispecific Antibody Therapy
核心洞察
A meta-analysis of 20 studies with 2,551 patients found a 3.5% rate of second primary malignancies following T-cell–engaging bispecific antibody therapy at a median follow-up of 17.4 months.
Second primary malignancies led to treatment discontinuation in 2.2% of patients and death in 1.4%, highlighting the clinical significance of this adverse event.
Nonmelanoma skin cancers and hematologic malignancies including myelodysplastic syndromes (搜索) and acute myeloid leukemias (搜索) were the most commonly identified second primary malignancies.
A systematic review and meta-analysis published in JAMA Oncology has identified second primary malignant neoplasms as a "clinically relevant complication" of treatment with T-cell–engaging bispecific antibodies (搜索) (BsAbs) in patients with non-Hodgkin lymphoma (搜索) or multiple myeloma (搜索). The findings, reported by Tomasik et al, underscore the need for standardized long-term safety monitoring as these therapies become increasingly integrated into hematologic malignancy treatment paradigms.
The analysis pooled data from clinical trials and real-world studies reported through October 1, 2025, encompassing 20 studies with 26 cohorts and a total of 2,551 patients.
Quantifying the Risk
Among eight studies comprising 10 cohorts and 1,003 patients that reported total second primary malignancies, the overall rate was 3.5% (95% CI = 1.8%–6.9%) at a median follow-up of 17.4 months (range = 5.7–25.6 months). When stratified by disease type, rates were 3.8% (95% CI = 2.3%–6.3%) among patients with non-Hodgkin lymphoma (搜索) and 3.4% (95% CI = 0%–76.7%) among those with multiple myeloma (搜索).
In a prespecified analysis incorporating study-level covariates—including follow-up duration, disease category, prior therapy courses, and patient age—no variables were found to be significantly associated with total second primary malignancy estimates.
Spectrum of Second Primary Malignancies
The second primary malignancies identified in the analysis included nonmelanoma skin cancers (n = 9) and hematologic malignant neoplasms (n = 7). Among the hematologic malignancies, myelodysplastic syndromes (搜索) accounted for four cases and acute myeloid leukemias (搜索) for two. The remaining cases consisted of heterogeneous solid tumors with no predominant subtype emerging from the data.
Clinical Consequences
The clinical impact of these second primary malignancies was further quantified. 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%). Across 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%).
Call for Standardized Surveillance
The investigators emphasized that despite the relatively short follow-up duration captured in the analysis, second primary malignancies represent a measurable and clinically relevant complication of BsAb therapy. They highlighted that heterogeneous and inconsistent reporting across studies currently complicates comprehensive assessment of this risk, underscoring the need for standardized long-term safety surveillance in clinical trials examining bispecific antibodies.
Roni Shouval, MD, PhD, of the Department of Medicine at Memorial Sloan Kettering Cancer Center in New York, served as the corresponding author for the JAMA Oncology article.