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

The study cohort of double-hit multiple myeloma patients with concurrent 1q21+ and t(4;14) had a median age of 62 years and predominantly presented at advanced disease stage.

• 96 newly diagnosed DHMM patients were included, with median age 62 (range: 36-79) years.
• 50 cases (52%) were at R2-ISS stage IV.
• 11 cases (11%) had concurrent del(17p).
• Patients were treated at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from September 2014 to September 2024.

The median progression-free survival was 26 months and the estimated median overall survival was 4.3 years in DHMM patients with concurrent 1q21+ and t(4;14).

• Median PFS was 26 months (95% CI: 22-50 months).
• Estimated median OS was 4.3 years (95% CI: 2.1-6.4 years).
• Median follow-up was 36 months (range: 6-126 months).
• 22 cases (23%) experienced extramedullary relapse.

Newly diagnosed extramedullary involvement of soft tissue was an independent risk factor for both PFS and OS in DHMM patients.

• Multivariate analysis identified newly diagnosed extramedullary soft tissue involvement as an independent risk factor for both PFS and OS (all P<0.05).
• Del(17p) was found to shorten PFS.
• MRD negativity significantly prolonged PFS.
• 22 cases (23%) had extramedullary relapse during follow-up.

Triple-agent induction therapy (PI+IMiD+CD38Ab) and auto-HSCT were both associated with improved MRD-negative rates.

• 39 cases (41%) received triple-agent induction therapy with PI+IMiD+CD38Ab.
• 35 cases (36%) underwent auto-HSCT.
• 25 cases (26%) achieved MRD-negative complete response (CR).
• Logistic regression analysis showed both triple-agent induction therapy and auto-HSCT improved MRD-negative rates (all P<0.05).

The clone size of 1q21+ was positively correlated with that of t(4;14), but the clonal burden of 1q21+ was significantly lower than that of t(4;14).

• Clone size of 1q21+ and t(4;14) were positively correlated (r=0.46, P<0.001).
• The clonal burden of 1q21+ was significantly lower than that of t(4;14).
• This finding suggests these two abnormalities may arise in a clonally related but hierarchically ordered manner.

Triple-agent induction therapy and auto-HSCT were associated with improved MRD negativity and PFS, but long-term survival remained challenging.

• Both PI+IMiD+CD38Ab induction and auto-HSCT improved MRD-negative rates (P<0.05 for both).
• MRD negativity was associated with significantly prolonged PFS.
• Despite these improvements, the paper concludes that 'achieving long-term survival remains challenging for these patients.'
• The study explored effective strategies to improve outcomes of this high-risk subgroup.