title: Outcomes in patients with multiple myeloma with TP53 deletion after autologous hematopoietic stem cell transplant.
abstract: TP53 gene deletion is associated with poor outcomes in multiple myeloma (MM). We report the outcomes of patients with MM with and without TP53 deletion who underwent immunomodulatory drug (IMiD) and/or proteasome inhibitor (PI) induction followed by autologous hematopoietic stem cell transplant (auto-HCT). We identified 34 patients with MM and TP53 deletion who underwent IMiD and/or PI induction followed by auto-HCT at our institution during 2008-2014. We compared their outcomes with those of control patients (n = 111) with MM without TP53 deletion. Median age at auto-HCT was 59 years in the TP53-deletion group and 58 years in the control group (P = 0.4). Twenty-one patients (62%) with TP53 deletion and 69 controls (62%) achieved at least partial remission before auto-HCT (P = 0.97). Twenty-three patients (68%) with TP53 deletion and 47 controls (42%) had relapsed disease at auto-HCT (P = 0.01). Median progression-free survival was 8 months for patients with TP53 deletion and 28 months for controls (P < 0.001). Median overall survival was 21 months for patients with TP53 deletion and 56 months for controls (P < 0.001). On multivariate analysis of both groups, TP53 deletion (hazard ratio 3.4, 95% confidence interval 1.9-5.8, P < 0.001) and relapsed disease at auto-HCT (hazard ratio 2.0, 95% confidence interval 1.2-3.4, P = 0.008) were associated with a higher risk of earlier progression. In MM patients treated with PI and/or IMiD drugs, and auto-HCT, TP53 deletion and relapsed disease at the time of auto-HCT are independent predictors of progression. Novel approaches should be evaluated in this high-risk population. Am. J. Hematol. 91:E442-E447, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sameh
authors.initials: S
authors.lastname: Gaballa
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Rima M
authors.initials: RM
authors.lastname: Saliba
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Samer
authors.initials: S
authors.lastname: Srour
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Gary
authors.initials: G
authors.lastname: Lu
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Brammer
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Nina
authors.initials: N
authors.lastname: Shah
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Qaiser
authors.initials: Q
authors.lastname: Bashir
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Krina
authors.initials: K
authors.lastname: Patel
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Fabian
authors.initials: F
authors.lastname: Bock
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Simrit
authors.initials: S
authors.lastname: Parmar
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Chitra
authors.initials: C
authors.lastname: Hosing
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Uday
authors.initials: U
authors.lastname: Popat
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ruby
authors.initials: R
authors.lastname: Delgado
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Rondon
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jatin J
authors.initials: JJ
authors.lastname: Shah
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Elisabet E
authors.initials: EE
authors.lastname: Manasanch
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas. mqazilba@mdanderson.org.
authors.forename: Muzaffar H
authors.initials: MH
authors.lastname: Qazilbash
mesh_terms: D000328:Adult; D000368:Aged; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D017353:Gene Deletion; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D061988:Proteasome Inhibitors / Q000627:therapeutic use; D012008:Recurrence; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D007155:Immunologic Factors; D061988:Proteasome Inhibitors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53