Outcomes of de novo del(17p) in multiple myeloma.

Abstract

e19558 Background: Del(17p) (de novo) occurring in up to 10% of newly diagnosed myeloma patients is an independent risk factor for shorter progression free survival (PFS) and overall survival (OS). Current definitions for high-risk myeloma per R-ISS and more recently updated IMS/IMWG consensus support del(17p) as a poor prognostic factor with inferior outcomes. Several studies have evaluated outcomes of patients with de novo del(17p), however, limited data exists on impact of other concomitant cytogenetic abnormalities on outcomes of these patients. In this large retrospective analysis, we present long-term outcomes of patients with de novo del(17p) with concomitant cytogenetic abnormalities. Methods: Among 421 myeloma patients identified with del(17p), 164 patients had de novo del(17p), defined as presence of del(17p) at myeloma diagnosis. Descriptive analyses were performed within the de novo del(17p) cohort, including evaluation of associated abnormalities. Survival outcomes were estimated using Kaplan–Meier method and compared with log-rank tests. Univariate Cox proportional hazards models were used to assess associations with PFS and OS. Statistical analyses performed using SAS version 9.41, with significance set at p < 0.05. Results: In the overall evaluable cohort of del(17p) patients (N = 388), with a median follow-up of 114 months, median PFS was 30 months, and median OS was 74.4 months. For patients with de novo del(17p) (N = 164), 48% were females, 42% were black. With median follow-up of 94.8 months, median PFS was 26.4 months and median OS was 56.4 months. Univariate analysis revealed inferior PFS in del(17p) in combination with gain(1q) [HR 2.24, 95%CI 1.54-3.26], complex karyotype [HR 1.49, 95%CI 1.02-2.18], circulating plasma cells [HR 3.02, 95%CI 1.72-5.28] and extramedullary disease [HR 1.86, 95%CI 1.21-2.86] and superior PFS with hyperdiploidy [HR 0.65, 95%CI 0.45-0.94] and interestingly with autologous stem cell transplant (ASCT) [HR 0.58, 95%CI 0.39-0.88]. Univariate analysis revealed inferior OS in del(17p) in combination with gain(1q) [HR 2.12, 95%CI 1.39-3.24], del(13q) [HR 1.83, 95%CI 1.15-2.93], %plasma cells with del(17p) ≥20 vs < 20% [HR 2.52, 95%CI 1.37-4.63], complex karyotype [HR 1.81, 95%CI 1.18-2.78], circulating plasma cells [HR 3.88, 95%CI 2.16-6.97] and extramedullary disease [HR 2.19, 95%CI 1.38-3.46] and superior OS with hyperdiploidy [HR 0.56, 95%CI 0.37-0.84] and ASCT [HR 0.61, 95%CI 0.38-0.98]. Conclusions: De novo del(17p) combined with gain(1q), complex karyotype, circulating plasma cells, extramedullary disease had inferior PFS and OS while hyperdiploidy and ASCT were associated with superior PFS and OS. Del(13q) and %plasma cells with del(17p) ≥20% were associated with inferior OS. Further evaluation of the dataset might enable us to unfold the differential prognostic outcomes of patients with de novo del(17p) and develop therapeutic strategies to overcome their poor prognostic significance.