Outcome of Patients with Multiple Myeloma and CKS1B Gene Amplification after Autologous Hematopoietic Stem Cell Transplantation

Outcome of Patients with Multiple Myeloma and CKS1B Gene Amplification after Autologous Hematopoietic Stem Cell Transplantation

Transplantation and Cellular Therapy, September 2016

27638366

Fabian Bock, Gary Lu, Samer A. Srour, Sameh Gaballa, Heather Y. Lin, Veerabhadran Baladandayuthapani, Medhavi Honhar, Maximilian Stich, Nina Das Shah, Qaiser Bashir, Krina Patel, Uday Popat, Chitra Hosing, Martin Korbling, Ruby Delgado, Gabriela Rondon, Jatin J. Shah, Sheeba K. Thomas, Elisabet E. Manasanch, Berend Isermann, Robert Z. Orlowski, Richard E. Champlin, Muzaffar H. Qazilbash

The gain/amplification of the CKS1B gene on chromosome 1q21 region is associated with a poor outcome in patients with multiple myeloma (MM). However, there are limited data on the outcome of patients with CKS1B amplification after a single high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT). We retrospectively evaluated the outcome of patients with CKS1B amplification who received an auto-HCT between June 2012 and July 2014 at our institution. We identified 58 patients with MM and CKS1B gene amplification detected by fluorescent in situ hybridization (FISH). We compared their outcomes with a propensity score matched control group of 58 patients without CKS1B amplification that were treated at approximately the same time. The primary objective was to compare the progression-free (PFS) and overall survival (OS) between the CKS1B and the control group. Stratified log-rank test with the matched pairs as strata and double robust estimation under the Cox model were used to assess the effect of CKS1B gene amplification on PFS or OS in the matched cohort. Patients in the CKS1B and control groups were well matched for age, gender, disease status, year of auto-HCT, response to pre-transplant therapy and baseline hemoglobin level. In both groups, 57% patients were in first remission and 43% had relapsed disease at auto-HCT. Twenty-seven (47%) patients with CKS1B amplification had concurrent monosomy 13 or 13q deletion [del(13q)]; 6 (10%) by conventional cytogenetics only, 16 (28%) by FISH only, and 5 (9%) by both. Median follow up after auto-HCT was 25.4 months. The median PFS of the CKS1B and the control group were 15.0 months and 33.0 months (p= 0.002), respectively. The median OS have not been reached yet. The 2-year OS rates in the CKS1B and the control group were 62% and 91% (p=0.02), respectively. In conclusion, Patients with CKS1B amplification are more likely to have additional high-risk cytogenetic abnormalities, and a shorter PFS and OS after an auto-HCT.