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Clinical implications of cytogenetic heterogeneity in multiple myeloma patients with TP53 deletion.


ABSTRACT: TP53 deletion (?TP53) in myeloma is known to be a high-risk finding associated with poorer prognosis. The prognostic impact of underlying cytogenetic heterogeneity in patients with myeloma associated with ?TP53 is unknown. We studied 90 patients with myeloma associated with ?TP53 identified by interphase fluorescence in situ hybridization and assessed the impact of karyotype and coexisting alterations of IGH, RB1, and CKS1B. There were 54 men and 36 women with a median age of 59 years (range 38-84); 14 patients had a normal karyotype (NK/?TP53), 73 had a complex karyotype (CK/?TP53), and 3 had a non-complex abnormal karyotype. Patients with CK/?TP53 showed a significantly poorer overall survival compared with patients with NK/?TP53 (P=0.0243). Furthermore, in the CK/?TP53 group, patients with IGH rearrangement other than t(11;14)(q13;q32)/CCND1-IGH, designated as adverse-IGH, had an even worse outcome (P=0.0045). In contrast, RB1 deletion, CKS1B gain, ploidy, additional chromosome 17 abnormalities, or ?TP53 clone size did not impact prognosis. Stem cell transplant did not improve overall survival in either the NK/?TP53 or CK/?TP53 (P=0.8810 and P=0.1006) groups, but tandem stem cell transplant did improve the overall survival of patients with CK/?TP53 (P=0.0067). Multivariate analysis confirmed in this cohort that complex karyotype (hazard ratio 1.976, 95% CI 1.022-3.821, P=0.043), adverse-IGH (hazard ratio 3.126, 95% CI 1.192-8.196, P=0.020), and tandem stem cell transplant independently correlate with overall survival (hazard ratio 0.281, 95% CI 0.091-0.866, P=0.027). We conclude that comprehensive genetic assessment adds to TP53 status in the risk stratification of myeloma patients.

SUBMITTER: Hao S 

PROVIDER: S-EPMC5628266 | BioStudies | 2017-01-01T00:00:00Z

REPOSITORIES: biostudies

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