Baseline characteristics, chromosomal alterations, and treatment affecting prognosis of deletion 17p in newly diagnosed myeloma

Abstract

Deletion 17p13, del(17p), is associated with poor outcome in myeloma but some patients show long-term survival. With the current study we intended to identify factors impacting outcome of such high risk patients. We analyzed 110 newly diagnosed, symptomatic patients with del(17p) detected by fluorescence in situ hybridization (FISH) in CD138-purified myeloma cells to identify prognostic factors for survival. Age >65 years, ISS III, and elevated LDH negatively impacted survival. Patients with subclonal (10-60% of plasma cells) del(17p) had longer progression-free survival (PFS) than patients with del(17p) in >60% of plasma cells (26 vs. 19 months, P = 0.03). Additional gain of 1q21 was associated with shorter PFS (17 vs. 25 months, P = 0.01). Hyperdiploidy did not ameliorate impact of del(17p), but gain 19q13 predicted longer PFS (30 vs. 18 months, P = 0.01) and overall survival (50 vs. 29 months, P = 0.01). Multivariate analysis in transplant eligible patients (≤65 years) revealed better survival for patients treated with upfront autologous transplantation (hazard ratio, [95% confidence interval]: 0.15 [0.04, 0.58], P = 0.006). Application of maintenance therapy was associated with better survival in transplant-eligible patients (0.30 [0.09, 0.99], P = 0.05). We demonstrate heterogeneous outcome of patients with del(17p) according to baseline characteristics and treatment. 19q13 should be included in routine FISH panel, since gains were associated with better survival. Am. J. Hematol. 91:E473-E477, 2016. © 2016 Wiley Periodicals, Inc.

Validation of multiple myeloma risk stratification indices in routine clinical practice: Analysis of data from the Czech Myeloma Group Registry of Monoclonal Gammopathies

“…It has been recently suggested that the clone size plays major role in prognosis of patients with del(17p). The patients with 10%‐60% of del(17p) were shown to have longer survival as published by Merz et al21 in their recent work. An et al22 suggested similar cutoff of 50% in their work.…”

The level of deletion 17p and bi-allelic inactivation of TP53 has a significant impact on clinical outcome in multiple myeloma

“…The impact of this variability on clinical outcomes has been uncertain with the importance having been addressed by only a few research groups. 1,8,9 The…”

“…1,8,9 Experimentally the value for the number of positive cells in this test was established based on the background detection rate of false positive signals in cells lacking the abnormality. In clinical studies it is clear that del17p is present at different percentages within the plasma cell population.…”

“…[1][2][3] MM is initiated by a number of genetic events, which sets a background upon which alterations associated with disease progression are superimposed. 4,5 Deletion of the short arm of chromosome 17 (del17p) is an independent prognostic marker associated with poor clinical outcome, as identified by a number of studies, and more recently it has been incorporated into risk stratification models.…”

Prognostic significance of cytogenetic heterogeneity in patients with newly diagnosed multiple myeloma

“…Additionally, recent studies in patients with deletion 17p demonstrated that higher cutoffs for the aberration (eg, 60% instead of 10% as in our routine practice) resulted in significantly shorter PFS, whereas results for OS were less significant. 20,21 In that context, longitudinal iFISH analyses might help identify distinct clones that are susceptible to certain agents. 22 In line with that hypothesis, we show that bortezomib might overcome the poor prognostic impact of gain 1q21 and deletion 17p if there are no additional subclones.…”