Abstract
Fluorescence in situ hybridization evaluation is essential for initial risk stratification in multiple myeloma. While the presence of specific cytogenetic high-risk abnormalities (HRA) is known to confer a poor prognosis, less is known about the cumulative effect of multiple HRA. We studied 1181 patients with newly diagnosed multiple myeloma who received novel agents as first-line therapy. High-risk abnormalities were defined as t(4;14), t(14;16), t(14;20) and del(17p). There were 884 patients (75%) without any HRA and 297 patients (25%) with HRA, including 262 (22%) with one HRA and 35 (3%) with two HRA. The presence of one HRA (versus zero, hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.32–2.05, p<0.001) and the presence of two HRA (versus zero, HR 3.15, 95% CI 2.00–4.96, p<0.001) were of prognostic significance after adjusting for other prognostic factors. Abnormalities of chromosome 13 were of prognostic significance independent of the established HRA: Monosomy 13 (HR 1.27, 95% CI 1.04–1.56, P=0.022) and del(13q) (HR 0.48, 95% CI 0.28–0.81, P=0.006) with opposite effects. Patients with HRA experienced worse overall survival suggesting a cumulative adverse effect of multiple HRA. Abnormalities of chromosome 13 were of prognostic significance after adjusting for other prognostic factors.
Highlights
Cytogenetic evaluation using fluorescence in situ hybridization (FISH) at the time of diagnosis is essential for initial risk stratification in multiple myeloma.1,2 The presence of specific cytogenetic high-risk abnormalities (HRA) including t(4;14), t(14;16), t(14;20), del(17p) and dup(1q) is known to confer a poor prognosis.3 Proteasome inhibition seems to improve outcomes in patients with t(4;14) and del(17p) while the effect on other HRA is less clear.4,5 These improvements in outcomes were observed for t(4;14) and del(17p) occurring in isolation but not for the presence of both abnormalities.6 Patients are usually considered high-risk based on the presence of any one of the known HRA, given the observed adverse impact on survival outcomes
The introduction of novel agents including immunomodulators and proteasome inhibitors has led to significant improvements in overall survival for patients with multiple myeloma
Patients with high-risk multiple myeloma do not seem to benefit from these new treatments as much as patients with standard-risk disease
Summary
Cytogenetic evaluation using fluorescence in situ hybridization (FISH) at the time of diagnosis is essential for initial risk stratification in multiple myeloma. The presence of specific cytogenetic high-risk abnormalities (HRA) including t(4;14), t(14;16), t(14;20), del(17p) and dup(1q) is known to confer a poor prognosis. Proteasome inhibition seems to improve outcomes in patients with t(4;14) and del(17p) while the effect on other HRA is less clear. These improvements in outcomes were observed for t(4;14) and del(17p) occurring in isolation but not for the presence of both abnormalities. Patients are usually considered high-risk based on the presence of any one of the known HRA, given the observed adverse impact on survival outcomes. The presence of specific cytogenetic high-risk abnormalities (HRA) including t(4;14), t(14;16), t(14;20), del(17p) and dup(1q) is known to confer a poor prognosis.. Patients are usually considered high-risk based on the presence of any one of the known HRA, given the observed adverse impact on survival outcomes. We aimed to evaluate the prognostic implications of the presence of chromosome 13 abnormalities and the established HRA in patients with newly diagnosed multiple myeloma treated with novel agents, taking into account other known prognostic factors. We retrospectively studied 1181 patients who were diagnosed with multiple myeloma between July 2005 and July 2015 at Mayo Clinic Rochester, underwent FISH evaluation within six months of diagnosis, and received first-line therapy with at least one novel agent (immunomodulator or proteasome inhibitor).
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