[Clinical characteristics and prognosis analysis of newly diagnosed multiple myeloma with t (4;14)]

Objective: This study aimed to analyze the clinical characteristics and prognosis of patients with newly diagnosed multiple myeloma (NDMM) with t (4;14) . Methods: Data of 431 patients with NDMM diagnosed in the First Affiliated Hospital of Nanjing Medical University between April 2017 and October 2024 were retrospectively analyzed. Cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization was used for cytogenetic testing to analyze the clinical characteristics and prognosis of patients with t (4;14) . Results: Among the enrolled patients, 69 (16.0%) were positive for t (4;14), and 362 (84.0%) were negative. Compared with the t (4;14) -negative group, patients in the t (4;14) -positive group demonstrated significantly higher proportions of IgG subtype, thrombocytopenia, and concomitant gain/amplification of chromosome 1q21 (all P<0.05). The median progression-free survival (PFS) of patients with t (4;14) was significantly shorter than that of patients with negative t (4;14) (27 months vs 39 months, P=0.014). However, no statistically significant difference in median overall survival (OS) was observed between the two groups (not reached vs not reached, P=0.056). Among the 69 patients with t (4;14), 18 had isolated t (4;14) and 51 had concomitant high-risk cytogenetic abnormalities (HRCA), including 50 patients with 1q21 gain/amplification or 1p32 deletion. The median PFS was 33 (95% CI: 24-42) months in patients with isolated t (4;14) and 26 (95% CI: 16-41) months in those with t (4;14) plus HRCA, whereas the median OS was not reached in either group. Patients with t (4;14) combined with HRCA demonstrated inferior PFS and OS compared with the t (4;14) -negative group (P=0.030 and P=0.026, respectively). Among patients with t (4;14), 25 underwent early autologous hematopoietic stem cell transplantation and demonstrated a trend toward longer median PFS compared with those who did not undergo transplantation [41 (95% CI: 14- not reached) months vs 26 (95% CI: 18-35) months], although the difference was not statistically significant (P=0.135). Treatment response was assessed in 22 transplanted patients, revealing that the rate of ≥ complete response increased from 40.9% before transplantation to 63.6% at 3 months post-transplantation, and the rate of ≥ very good partial response increased from 81.8% to 90.9%. Multivariate Cox regression analysis after adjustment for treatment-related factors identified that t (4;14) remained an independent adverse prognostic factor for PFS in patients with NDMM (HR=1.608, 95% CI: 1.103-2.346, P=0.014), but not for OS. Conclusion: In the era of novel agents, t (4;14) was identified as an independent risk factor for PFS in patients with NDMM, although it did not significantly affect OS. Patients with t (4;14) combined with other HRCA demonstrated a worse prognosis.