Complex karyotype and translocation t(4;14) define patients with high-risk newly diagnosed multiple myeloma: results of CMG2002 trial.

The prognostic impact of chromosomal abnormalities was evaluated by fluorescence in situ hybridization with cytoplasmic immunoglobulin light chain staining (cIg-FISH) and by classical metaphase cytogenetics in a cohort of 207 patients with newly diagnosed multiple myeloma who were treated with high-dose therapy followed by autologous stem cell transplantation in the CMG2002 clinical trial. The incidence of chromosomal abnormalities detected by FISH was as follows: 52.7% for del(13)(q14), 6.5% for del(17)(p13), 18.6% for t(11;14)(q13;q32), 22.8% for t(4;14)(p16;q32) and 45.7% for gain(1)(q21). Metaphase cytogenetic analysis revealed a complex karyotype in 19.1% and hyperdiploidy in 21.7% of patients. The overall response rate was not influenced by the presence of any studied chromosomal abnormality. Patients with a complex karyotype, those with translocation t(4;14) and those with gain of the 1q21 locus had a shorter time to progression (TTP) and overall survival (OS). Other genomic changes such as translocation t(11;14) and del(13q) had less impact on TTP and OS. In multivariate analysis, complex karyotype, translocation t(4;14) and ß(2)-microglobulin level > 2.5 mg/L were independent prognostic factors associated with poor overall survival. Their unfavorable prognostic impact was even more pronounced if they were present in combination. Patients with t(4;14) present together with a complex karyotype had the worst prognosis, with a median OS of only 13.2 months, whereas patients with a normal karyotype or karyotype with ≤ 2 chromosomal changes had the best outcome, with 3-year OS of 85.9%. In conclusion, complex karyotype, gain of 1q21 region and translocation t(4;14) are major prognostic factors associated with reduced survival of patients with newly diagnosed multiple myeloma treated with autologous stem cell transplantation.

Long-term outcomes of autologous transplantation in multiple myeloma: significant survival benefit of novel drugs in post-transplantation relapse.

BACKGROUND: Autologous stem cell transplantation (autoSCT) has an important role in the treatment of patients with symptomatic multiple myeloma (MM). Treatment options for myeloma have expanded in the past decade, and it seems that patients who are treated with novel drugs such as thalidomide and bortezomib for relapse after autoSCT have longer overall survival (OS). PATIENTS AND METHODS: Herein, we describe the long-term outcome of a cohort of 185 patients with newly diagnosed MM treated with autoSCT. We have analyzed factors that might predict for long-term survival. RESULTS: Following autoSCT, the overall response rate was 94% (173 of 185 patients); 29% (53 of 185 patients) were in complete remission (CR). Median time to progression (TTP) and OS from start of therapy were 39.8 months and 77.9 months, respectively. The median follow-up was 103.8 months (range, 60.8-144.8 months); 23% of the patients are alive and disease free, 21% of the patients are alive with relapse, and 56% of the patients have died. On multivariate analysis, factors associated with significantly better OS were International Staging System (ISS) disease stage < III (hazard ratio [HR], 2.6; P < .001), achievement of CR after autoSCT (HR, 2.8; P < .001) and use of thalidomide (HR, 4.3; P < .001) and/or bortezomib (HR, 7.3; P < .001) in posttransplantation relapse treatment. The patients' age, renal impairment, disease status before autoSCT and maintenance therapy with interferon-alpha (IFN-alpha) or IFN-alpha and dexamethasone did not significantly affect TTP and OS after transplantation. CONCLUSION: According to our results, the achievement of CR after transplantation, ISS stage other than III, and administration of thalidomide or bortezomib in posttransplantation relapse were significant parameters favoring long-term posttransplantation survival.