Patients With MCL and a Specific Mutation in Need of Alternative Frontline Therapies

Submitted by admin5 on Mon, 08/21/2017 - 14:47

Patients with mantle cell lymphoma (MCL) should be stratified based on the status of a specific mutation and considered for alternative first-line therapy, according to a new study published in Blood (online August 18, 2017; doi:10.1182/blood-2017-04-779736).

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Recent advancements in lymphoma therapy have revolutionized the treatment landscape. However, MCL remains an incurable blood cancer and clinicians are still unable to identify at diagnosis the patients who will not benefit from the current standard-of-care (involving cytarabine, rituximab, or autologous stem-cell transplantation).

A group of multinational researchers led by Christian W Eskelund, department of hematology, Copenhagen University Hospital (Denmark), conducted a study to examine the prognostic value of recurring genetic aberrations in diagnostic bone marrow specimens of younger patients with MCL. A total of 183 patients were selected for the analysis from the Nordic MCL2 and MCL3 trials, which represent current standard-of-care regimens.

A univariate model showed mutations of TP53 (11%) and NOTCH1 (4%), along with deletions of TP53 (16%) and CDKN2A (20%) were significantly associated with inferior outcomes in these trials. However, multivariate analysis showed that only TP53 mutations (HR, 6.2; P < .0001) and MIPI-c high-risk (HR, 2.6; P = .003) demonstrated independent prognostic implications on time to relapse.

After their analysis, researchers reported that patients with TP53-mutated MCL had poor prognosis; the median overall survival among these patients was 1.8 years and 50% of patients relapsed after 1.0 years (compared to not reached and 12.7 years, respectively, in patients without the mutation; P < .0001).

Additionally, researchers reported that TP53 mutations were strongly associated with Ki67 greater than 30%, blastoid morphology, MIPI-c high-risk, and inferior responses to both induction and high-dose chemotherapy.  

Authors of the study concluded that TP53 mutations classify a phenotypically distinct and highly aggressive form of MCL with poor or no response to current standard-of-care. They suggest that patients with MCL should be stratified according to TP53 status, and that patients with TP53 mutations should be considered for experimental frontline trials assessing novel agents.—Zachary Bessette