Ps1400 Assessment of Survival in Patients With Newly Diagnosed Multiple Myeloma by Using Modified Risk Stratification Msmart 3.0

Abstract

Background: Studies over the past decade, have greatly improved our understanding of the molecular basis of multiple myeloma and mechanisms of disease progression. Metaphase cytogenetics and fluorescence in situ hybridization (FISH) help us to identify the most frequent genetic abnormalities. The division of patients into various risk groups based on the chromosomal markers is being utilized by many centers for select and optimize of therapeutic strategy. However, such molecular risk-stratification systems are repeatedly updated in accordance with the emergence of new information about the prognostic impact of anomalies. The role of complex karyotype and combination of genetic abnormalities remains unclear. Aims: To estimate the incidence of genetic abnormalities and their impact on overall and progression-free survival in patients with newly diagnosed multiple myeloma (NDMM). Methods: The study included 159 patients (median age 63 years, range 28 -83; male: female ratio -1:1.37) with NDMM. Metaphase cytogenetics on bone marrow samples was done by standard GTG-method. FISH analyses were performed according to the manufacturer's protocol for detection primary IgH translocations, 13q (13q14/13q34) deletion, 1p32/1q21 amplification/deletion, P53/cen 17 deletion (MetaSystems DNA probes). We additional searched the t(4;14), t(6;14), t(11;14), t(14;16) and t(14;20) in patients with IgH translocation. All patient was treated by bortezomib-based programs (VD, CVD, VMP, PAD). Results: The frequency of genetic abnormalities in NDMM patients was 49% (78/159). IgH translocation was detected in 26.4% (42/159) patients: t(11;14) -16.3% (26/159), t(4;14) -5.0% (8/159); TP53/del17p -5.6% (9/159); 1p32/1q21 amp/del -12% (19/159); hypodiploidy -3.1% (5/159); hyperdiploidy -1.25% (2/159); del5q -0,6% (1/159); other -not found. Combination two aberrations was discovered in 11.9% (19/159) patients, complex abnormalities (≥3 aberrations) -in 4.4% (7/159) patients. The median OS in "two aberration'' and "complex abnormalities'' groups were lower than in standard-risk mSMART 3.0 (normal, t(11;14), hypodiploidy, hyperdiploidy and other): 49 months, 37 months and not reached, respectively (p = .02). The median PFS for these groups was 12 months, 11 months and 30 months, respectively (p = 0.004). We modified high-risk mSMART 3.0 by adding "two aberration'' and "complex abnormalities'' groups on based the OS and PFS results. The median OS in standard-risk mSMART 3.0 was not reached, in high-risk mSMART 3.0 mod -50 months; 5-years OS was 65% and 38%, respectively (p = 0.01). The median PFS was 58 and 29 months, respectively (p = .02). Summary/Conclusion: Combination two aberrations and complex abnormalities are unfavorable prognostic markers. The median OS and PFS was higher in standard-risk than high-risk patients mSMART 3.0 mod . It can be useful for update risk stratification in future.