Background

Four BCMA-directed bispecific antibodies (BsAbs), teclistamab, talquetamab, elranatamab, and linvoseltamab,

are FDA-approved for relapsed/refractory multiple myeloma (RRMM) after at least four prior lines of therapy.

While immune-related toxicities and infections from these T-cell redirecting agents have been studied, the risk of

secondary primary malignancies (SPMs) is not well defined. We evaluated SPM frequency, characteristics, and

safety signals for the four BsAbs using real-world pharmacovigilance data.

Methods

We performed a retrospective analysis of the FDA Adverse Event Reporting System (FAERS) from Q4 2022 to Q4

2025. Cases reporting exposure to the four agents were classified by SPM status and grouped by cancer type

(hematologic, skin, lung/pleural, solid tumor, other). Reporting odds ratios (ROR) with 95% confidence intervals

were calculated for each drug using pooled data from the remaining three as comparators. Case fatality rates

(CFR) were calculated overall and by SPM status.

Results

Of 5419 cases (teclistamab: 2436; talquetamab: 1531; elranatamab: 1435; linvoseltamab: 17), 143 SPMs were

identified (2.6%). Teclistamab showed a significant disproportionality signal (ROR, 2.00; 95% CI, 1.42–2.81), with

skin cancers as the most common subtype (36.4%). Elranatamab (ROR, 0.64; 95% CI, 0.42–0.98) and talquetamab

(ROR, 0.61; 95% CI, 0.40–0.93) had significantly lower SPM reporting, with hematologic malignancies

most common (48.1% and 42.9%, respectively). Linvoseltamab had zero SPM reports among 17 cases, reflecting

limited post-marketing data. Overall CFR was 19.4% (1053/5419), with variation across drugs (teclistamab: 24.8%;

elranatamab: 21.3%; talquetamab: 9.3%; linvoseltamab: 0%). Pooled CFR for SPM cases was 22.4% (32/143).

Conclusion

These findings provide a baseline estimate of SPM burden with BsAbs in RRMM. Teclistamab is associated with a

significant SPM signal, mostly skin cancers, while elranatamab and talquetamab show lower signals with mostly

hematologic SPMs. This pattern suggests heterogeneity within the class rather than a uniform class-wide risk.

Linvoseltamab data are too limited for any meaningful assessment. Continued pharmacovigilance, inclusion of

SPM endpoints in clinical trials, and prospective long-term studies are warranted.

BCMA: B-cell maturation antigen, FDA: Food and Drug Administration

Keywords

MM, secondary primary malignancies, bispecific antibodies, multiple myeloma, teclistamab, talquetamab,

elranatamab, linvoseltamab, FAERS, pharmacovigilance