High Risk Cytogenetic Abnormalities Are Poor Prognostic Factors for Newly Diagnosed Multiple Myeloma Patients Received Autologous Hematopoietic Cell Transplantation

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Background High risk cytogenetic abnormalities (HRCA) are associated with the poor prognosis of multiple myeloma (MM). Del (17p), t(4;14) and t(14;16) are common HRCA in patients with MM. At present, the prognostic value of 1q21 gain/amplification (1q21+) in newly diagnosed MM (NDMM) patients who received autologous hematopoietic stem cell transplantation (ASCT) remains controversial. Methods: We enrolled 682 NDMM patients received ASCT in 25 MM research centers in China to detect cytogenetic abnormalities including 1q21 gain/amplification (1q21+), del17p13, t(14; 16), t(4; 14) and t(11; 14) by fluorescence in situ hybridization (FISH). HRCA was defined by the presence of at least del(17p), t(4;14), t(14;16) and/or 1q21+. Results: Of 682 patients included in this study, the median age was 55 (25-73) years, and the male to female ratio was 1.46 (405/277). Among 682 patients, 547 (80.2%) patients received FISH detection before induction therapy. The median follow-up time for all patients was 34.9 (range 5.1-167.0) months. The median overall survival (OS) estimated by the Kaplan-Meier method were 114.4 (95% CI, 103.1-125.6) months and the median progression-free survival (PFS) estimated were 57.6 (95% CI, 43.4-71.8) months. Six hundred and seventy achieved partial response (PR) or better and 43.1% (277/642) patients had CR (complete response) or stringent CR (sCR) before ASCT. After ASCT, 373 (62.7%) patients achieved CR or sCR and the remission rate of patients after ASCT was further improved compared with the pre-transplant efficacy (p value < 0.001). Patients without HRCA had longer OS than that had HRCA (not reached vs. 73.3 months, p<0.001, Figure 1B), and also had longer PFS than that had HRCA (not reached vs. 69.7 months, p<0.001). Univariate Cox proportional risk regression analysis showed that five factors associated with OS: male, hemoglobin (HGB) < 100g/L, lactate dehydrogenase (LDH) >250U/L, HRCA and International Staging System (ISS) stage III. Multivariate analysis was performed for these five covariates, serum creatinine (sCr) >2mg/dl and corrected serum calcium (CsCa) >2.75mmol/L. It was showed that HRCA was a poor factor for OS in the multivariate analysis (HR=1.671, 95%CI: 1.064-2.625, p=0.026). Multivariate analysis also showed that HRCA was a poor factor for PFS (HR=2.242, 95%CI: 1.592-3.158, p<0.001). Conclusion This multicenter study demonstrates that HRCA is a poor prognostic factor for survival of NDMM patients received ASCT.

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