Effect of daratumumab on patients with high-risk cytogenetic multiple myeloma: a systematic review and meta-analysis...

Although daratumumab has been reported to significantly improve the prognosis of multiple myeloma (MM), its efficacy in patients with cytogenetically high-risk MM (HRMM) remains unclear. This meta-analysis aims to evaluate the effect of daratumumab on progression-free survival (PFS) and overall survival (OS) in patients with cytogenetically HRMM. Compared to treatment without daratumumab, treatment with daratumumab showed significant PFS (HR = 0.58, P < 0.001) and OS (HR = 0.74, P = 0.017) benefit in patients with cytogenetically HRMM. Subgroup analyses revealed similar PFS benefits for newly diagnosed MM (HR = 0.63, P < 0.001), relapsed or refractory MM (HR = 0.53, P < 0.001), subcutaneous daratumumab (HR = 0.69, P = 0.038), and intravenous daratumumab (HR = 0.53, P < 0.001). Meanwhile, daratumumab significantly improved PFS in patients with revised high cytogenetic risk (HR = 0.51, P < 0.001). Another subgroup analysis revealed that daratumumab significantly improved PFS in both the one high-risk cytogenetic abnormality (HRCA) group (HR = 0.46, P < 0.001) and the isolated gain/amp(1q21) group (HR = 0.49, P < 0.001), while no significant improvement in PFS was observed in the group with more than or equal to two HRCAs (HR = 0.64, P = 0.212). However, sensitivity analysis showed that the beneficial OS is not robust. These results suggested that incorporating daratumumab into treatment regimens for patients with cytogenetic HRMM resulted in improved PFS. However, the effect of daratumumab on PFS may depend on HRCAs status. Additionally, the OS findings were suggestive of a potential benefit but require validation in future trials.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251244272.