Despite recent advances in lymphoma treatment, mantle cell lymphoma (MCL) remains incurable, and we are still unable to identify patients who will not benefit from the current standard of care. Here, we explore the prognostic value of recurrent genetic aberrations in diagnostic bone marrow (BM) specimens from 183 younger patients with MCL from the Nordic MCL2 and MCL3 trials, which represent current standard-of-care regimens. In the univariate model, mutations of (11%) and (4%), and deletions of (16%) and (20%), were significantly associated with inferior outcomes (together with MIPI, MIPI-c, blastoid morphology, and Ki67 > 30%); however, in multivariate analyses, only mutations (HR, 6.2; < .0001) retained prognostic impact for overall survival (OS), whereas mutations (HR, 6.9; < .0001) and MIPI-c high-risk (HR, 2.6; = .003) had independent prognostic impact on time to relapse. -mutated cases had a dismal outcome, with a median OS of 1.8 years, and 50% relapsed at 1.0 years, compared to a median OS of 12.7 years for -unmutated cases ( < .0001). mutations were significantly associated with Ki67 > 30%, blastoid morphology, MIPI high-risk, and inferior responses to both induction- and high-dose chemotherapy. In conclusion, we show that mutations identify a phenotypically distinct and highly aggressive form of MCL with poor or no response to regimens including cytarabine, rituximab, and autologous stem-cell transplant (ASCT). We suggest patients with MCL should be stratified according to status, and that patients with mutations should be considered for experimental frontline trials exploring novel agents.
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| http://dx.doi.org/10.1182/blood-2017-04-779736 | DOI Listing |
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