All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit the Lymphoma Coalition.
Introducing
Now you can personalise
your Lymphoma Hub experience!
Bookmark content to read later
Select your specific areas of interest
View content recommended for you
Find out moreThe Lymphoma Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the Lymphoma Hub cannot guarantee the accuracy of translated content. The Lymphoma Hub and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.
The Lymphoma & CLL Hub is an independent medical education platform, sponsored by Beigene and Roche, and supported through educational grants from Bristol Myers Squibb, Ipsen Biopharmaceuticals, Pfizer, and Pharmacyclics LLC, an AbbVie Company and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC View funders.
Bookmark this article
On 17th August, in Blood, Christian W. Eskelund from Rigshospitalet, Copenhagen, Denmark, and colleagues published findings on common genomic alterations in Mantle Cell Lymphoma (MCL) and how they impact prognosis in two, large Nordic trials: MCL2 and MCL3 (NCT00514475).
Patients were aged 66 years or less, had stage II-IV disease, and were considered fit for Autologous Stem Cell Transplant (ASCT). The regimen used in the MCL2 and MCL3 trials included induction of alternating R-maxi-CHOP and R-high-dose-cytarabine, subsequently followed with BEAM or BEAC high-dose chemotherapy and ASCT. Overall, 320 patients were enrolled onto the two trials; one patient withdrew from the MCL2 trial because of a change in diagnosis.
Overall, the authors stated that “TP53-mutated MCL represents a phenotypically distinct and highly aggressive disease entity”. Patients who harbor mutated TP53 have poor responses to high-dose regimens that include rituximab, cytarabine, and ASCT. The authors recommend stratifying patients by TP53 mutational status and should be studied separately in clinical trials that aim to explore novel targeted agents.
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 MCL patients from the Nordic MCL2 and MCL3 trials, which represent current standard-of-care regimens. In the univariate model, mutations of TP53 (11%) and NOTCH1 (4%), and deletions of TP53 (16%) and CDKN2A (20%) were significantly associated with inferior outcomes (together with MIPI, MIPI-c, Blastoid morphology and Ki67>30%); however, in multivariate analyses only TP53 mutations (HR=6.2, p<0.0001) retained prognostic impact for overall survival (OS), while TP53 mutations (HR=6.9, p<0.0001) and MIPI-c high-risk (HR=2.6, p=0.003) had independent prognostic impact on time to relapse. TP53-mutated cases had a dismal outcome with a median OS of 1.8 years and 50% relapsed at 1.0 years (compared to not reached (NR) and 12.7 years, respectively, for TP53-unmutated cases, p<0.0001). TP53 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 TP53 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 that MCL patients should be stratified according to TP53 status, and that patients with TP53 mutations should be considered for experimental frontline trials exploring novel agents.
Understanding your specialty helps us to deliver the most relevant and engaging content.
Please spare a moment to share yours.
Please select or type your specialty
Your opinion matters
Subscribe to get the best content related to lymphoma & CLL delivered to your inbox