[Clinical characteristics, treatment, and prognosis of double-hit multiple myeloma with concurrent 1q21+ and t (4;14)]

Objective: To analyze the clinical characteristics, therapeutic regimens, and prognosis of double-hit multiple myeloma (DHMM) patients with concurrent 1q21 copy number gain (1q21+) and t (4;14) , and to explore effective strategies to improve outcomes of this high-risk subgroup. Methods: A retrospective analysis was performed on 96 newly diagnosed DHMM patients with both 1q21+ and t (4;14) admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from September 2014 to September 2024. Baseline clinical characteristics, prognosis, and independent prognostic factors were evaluated. A logistic regression model was used to analyze the correlation between induction regimens, autologous hematopoietic stem cell transplantation (auto-HSCT) , and minimal residual disease (MRD) negativity. Results: The median age of the 96 DHMM patients was 62 (range: 36-79) years. Among them, 50 cases (52% ) were at R2-ISS stage Ⅳ, 11 cases (11% ) had concurrent del (17p) , 35 cases (36% ) underwent auto-HSCT, 39 cases (41% ) received triple-agent induction therapy with proteasome inhibitor (PI) , immunomodulatory drug (IMiD) and anti-CD38 monoclonal antibody (CD38Ab) , 25 cases (26% ) achieved MRD-negative complete response (CR) . The clone size of 1q21+ was positively correlated with that of t (4;14) (r=0.46, P<0.001) , while the clonal burden of 1q21+ was significantly lower than that of t (4;14) . With a median follow-up of 36 (range: 6-126) months, the median progression-free survival (PFS) was 26 (95% CI: 22-50) months, and the estimated median overall survival (OS) was 4.3 (95% CI: 2.1-6.4) years. Extramedullary relapse occurred in 22 cases (23% ) . Multivariate analysis showed that newly diagnosed extramedullary involvement of soft tissue was an independent risk factor for both PFS and OS (all P<0.05) . Del (17p) shortened PFS, whereas MRD negativity significantly prolonged PFS. Both triple-agent induction therapy (PI+IMiD+CD38Ab) and auto-HSCT improved the MRD-negative rate (all P<0.05) . Conclusion: DHMM patients with concurrent 1q21+ and t (4;14) exhibit aggressive clinical features and poor prognosis. Triple-agent induction therapy (PI+IMiD+CD38Ab) and auto-HSCT are associated with MRD negativity and improved PFS, but achieving long-term survival remains challenging for these patients.