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Predicting Clinical Outcomes of Patients With High-Risk MCL

Patients with high-risk mantle cell lymphoma (MCL) biology—defined by blastoid variance, Ki-67 greater than 30%, or high p53 immunohistochemistry expression—are more likely to experience shorter failure-free and overall survival, according to a study presented at the European Hematology Association (EHA) Annual Meeting (June 11-21, 2020).

MCL is characterized as a lymphoma subtype with a wide variance in clinical outcomes. Prospective trials have shown that disease cytology (classical type vs blastoid variant), cell proliferation as determined by Ki-67-expression, and p53 alterations should be considered indicators of high-risk disease.

Martin Dreyling, MD, professor of medicine, University of Munich Hospital (Germany), and colleagues designed an analysis to determine a biologically-based prognostic score for MCL that could lead to further risk-based therapeutic approaches in clinical trials. A total of 1229 patients with MCL from the MCL Younger and MCL Elderly trials were included in the analysis.

Researchers classified lymphomas as classical or blastic/pleomorphic variant and analyzed each case with Ki-67 or p53 immunohistochemistry. Patients were considered to have high-risk biology if they exhibited blastoid cytomorphology, Ki-67 greater than 30%, or high p53 staining that indicated a mutated gene status expression.

Dr Dreyling and colleagues utilized a control group of standard-risk patients (classical disease with Ki-67 less than 30% and p53 immunohistochemistry expression less than 50%) for comparison purposes.

In 365 of the patients, at least one of the biological parameters indicated a high-risk biology, or high-risk biology was excluded by determination of all three parameters. Sixty-five of 651 analyzed cases (10%) had blastoid cytomorphology, 175 of 591 cases (30%) had an increased Ki-67 greater than 30%, and 54 of 348 cases (16%) had mutated p53 status.

Patients in the standard-risk control cohort had a significantly higher median-free survival (6.3 vs 2.2 years, respectively; P < .0001) and overall survival (median not reached vs 4.5 years, respectively; P < .0001) compared with those in the high-risk biology cohort. This trend remained significant in both patients treated with conventionally-dosed chemotherapy (median progression-free survival, 3.8 vs 1.3 years, respectively) as well as patients receiving a cytarabine-containing induction regimen and autologous transplantation (median progression-free survival, 7.5 vs 3.7 years, respectively).

Authors of the study concluded that, “As these biological factors seem to dictate the sometimes dismal clinical course of MCL, we recommend to incorporate these factors in routine diagnostic practice.”—Zachary Bessette