Prognostic impact of hyperdiploidy in multiple myeloma patients with high-risk cytogenetics: a pilot study in China

Purpose: Multiple myeloma is genetically heterogeneous with varied clinical outcomes, primarily due to the coexistence of diverse numerical and structural cytogenetic abnormalities. The prognostic impact of hyperdiploidy in myeloma patients with high-risk cytogenetics remains controversial in Western studies and is unknown in China.

Methods: We examined the cytogenetic features of hyperdiploidy in 201 Chinese patients with newly diagnosed myeloma using magnetic-activated cell sorting and interphase fluorescence in situ hybridization and analyzed the effect of hyperdiploidy on the prognosis of patients with high-risk cytogenetics.

Results: Hyperdiploidy was detected in 50.7% (102/201) of the examined patients, and the incidence of hyperdiploidy coexisting with high-risk cytogenetics [del(17p13), +1q21 and adverse t(14q32)] was 33.8% (68/201). Survival analysis showed that the median progression-free survival (PFS) and 2-year overall survival (OS) of patients were better for hyperdiploidy than those for non-hyperdiploidy (43 vs. 20 months, P = 0.01; 86.8% vs. 70.5%, P = 0.04) and for standard-risk cytogenetics than those for high-risk cytogenetics (not reached vs. 23 months, P = 0.0001; 87.6% vs. 74.4%, P = 0.01). Strikingly, the high-risk cytogenetics patients with hyperdiploidy showed a better median PFS than those without hyperdiploidy (34 vs. 15 months, P = 0.01); however, compared to standard-risk cytogenetics patients, the median PFS and 2-year OS were poorer (34 months vs. not reached, P = 0.02; 78.8% vs. 87.6%, P = 0.05). The independent predictors of PFS were non-hyperdiploidy, high-risk cytogenetics, and bone marrow plasma cells ≥ 30%, with hazard ratios of 2.01 (95% CI 1.25-3.25), 2.56 (95% CI 1.38-4.74), and 1.81 (95% CI 1.08-3.05), respectively, and those for OS were non-hyperdiploidy and serum lactate dehydrogenase ≥ 250 U/L, with hazard ratios of 2.53 (95% CI 1.24-5.46) and 3.53 (95% CI 1.50-6.96), respectively.

Conclusions: These results suggest that the coexistence of hyperdiploidy may ameliorate the adverse prognosis of multiple myeloma patients with high-risk cytogenetics. High-risk cytogenetics patients without hyperdiploidy showed the worst prognosis.