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Immunotherapy: long-term benefits on survival and relapse in a rare lymphoma


New data from a major Phase 3 trial in mantle cell lymphoma (LYMA), led by Prof. Steven Le Gouill, hematologist and Director of Institut Curie Hospital Group, and Dr. Clémentine Sarkozy, hematologist at Institut Curie, reveal the long-term benefits of immuno-chemotherapy maintenance for 3 years after chemotherapy and autologous transplantation: over 75% of patients remained progression-free at 7 years. This work is published in the Journal of Clinical Oncology on December 18, 2023.


With some 200,000 people diagnosed each year worldwide, including around 600 in France, mantle cell lymphoma (MCL) accounts for 2-10% of lymphomas (cancers of the lymphatic system). These rare lymphomas entity affect the B lymphocytes of the immune system in a region of the lymph node known as the "mantle zone". Often aggressive with high recurrence rates, MCL affects men more than women, and more frequently those over the age of 65.

An extensive phase 3 study sparking change in standard treatment

In 2017, the findings to come out of an extensive phase 3 study (so-called LYMA[1] trial) coordinated by Prof. Steven Le Gouill, Director of Institut Curie Hospital Group, demonstrated that adding immunotherapy (rituximab, an anti-CD20 antibody, a specific marker for B lymphocytes) for three years following initial chemotherapy treatment, improves overall survival rates in patients with mantle-cell lymphoma (aged under 66 at the time of diagnosis) [2].

Five years ago, our findings changed the standard of care for mantle-cell lymphoma for patients under 65. Today, we are publishing the long-term data from the study, which are very positive: more survival without more side effect

Enthuses Prof. Steven Le Gouill.

75% of the patients who responded to immuno-chemotherapy had not progressed seven years later

The long-term results (seven years after treatment) show that the immunological benefits persist after treatment has been stopped in 75% of patients.

Our results also show that stopping maintenance treatment after 3 years does not increase the risk of relapse

Adds Dr. Sarkozy.

However, while the number of long-term recurrences dropped, it is important to note that around 15% of patients experience recurrence early, (within 2 years of starting treatment), with a poor prognosis at relapse. Identifying these patients as soon as they are diagnosed, in order to provide them with new therapeutic solutions, remains a crucial challenge.

Just a few years ago, median overall survival for patients with this rare form of lymphoma was around four years. Today, 75% of patients are alive seven years later, which points to considerable progress. Now, our goal is to identify the 15% of patients who are refractory to conventional approaches new protocols right from the beginning of treatment in order to provide them with suitable alternatives such as Car-T cells or bispecific antibodies...which still remain to be explored

Concludes Prof. Steven Le Gouill.

Reference: Long-term follow-up of rituximab maintenance in young patients with mantle cell lymphoma included in the LYMA trial, a LYSA study. Clémentine Sarkozy, Catherine Thieblemont, Lucie Oberic, Anne Moreau, Krimo Bouabdallah, Gandhi Damaj, Thomas Gastinne, Benoit Tessoulin, Vincent Ribrag, Olivier Casasnovas, Corinne Haioun, Roch Houot, Fabrice Jardin, Eric Van Den Neste, Morgane Cheminant, Franck Morschhauser, Mary Callanan, Violaine Safar, Remy Gressin, Olivier Hermine et Steven Le Gouill. Journal of Clinical Oncology. 18 décembre 2023 - DOI: 10.1200/JCO.23.01586


[1] The LYMA study was a multicenter, randomized Phase 3 trial in mantle cell lymphoma patients aged 18 to 65. This trial examined the efficacy of maintenance treatment with immunotherapy (rituximab) for 3 years, after induction treatment with chemotherapy followed by autograft. The study was coordinated by the LYSA lymphoma clinical research network.

[2]Rituximab after Autologous Stem-Cell Transplantation in Mantle-Cell Lymphoma. Steven Le Gouill, M.D., Ph.D. et al. for the LYSA Group. September 28, 2017. N Engl J Med 2017; 377:1250-1260 . DOI: 10.1056/NEJMoa1701769