Angioimmunoblastic T-cell lymphoma (AITL) is a frequent T-cell lymphoma in the elderly population that has a poor prognosis when treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy. Lenalidomide, which has been safely combined with CHOP to treat B-cell lymphoma, has shown efficacy as a single agent in AITL treatment. We performed a multicentric phase 2 trial combining 25 mg lenalidomide daily for 14 days per cycle with 8 cycles of CHOP21 in previously untreated AITL patients aged 60 to 80 years. The primary objective was the complete metabolic response (CMR) rate at the end of treatment. Seventy-eight of the 80 patients enrolled were included in the efficacy and safety analysis. CMR was achieved in 32 (41%; 95% confidence interval [CI], 30%-52.7%) patients, which was below the prespecified CMR rate of 55% defined as success in the study. The 2-year progression-free survival (PFS) was 42.1% (95% CI, 30.9%-52.8%), and the 2-year overall survival was 59.2% (95% CI, 47.3%-69.3%). The most common toxicities were hematologic and led to treatment discontinuation in 15% of patients. This large prospective and uniform series of AITL treatment data was used to perform an integrative analysis of clinical, pathologic, biologic, and molecular data. TET2, RHOA, DNMT3A, and IDH2 mutations were present in 78%, 54%, 32%, and 22% of patients, respectively. IDH2 mutations were associated with distinct pathologic and clinical features and DNMT3A was associated with shorter PFS. In conclusion, the combination of lenalidomide and CHOP did not improve the CMR in AITL patients. This trial clarified the clinical impact of recurrent mutations in AITL. This trial was registered at www.clincialtrials.gov as #NCT01553786.
About The Expert
François Lemonnier
Violaine Safar
Asma Beldi-Ferchiou
Anne-Ségolène Cottereau
Emmanuel Bachy
Guillaume Cartron
Virginie Fataccioli
Laura Pelletier
Cyrielle Robe
Audrey Letourneau
Edoardo Missiaglia
Slim Fourati
Marie-Pierre Moles-Moreau
Alain Delmer
Reda Bouabdallah
Laurent Voillat
Stéphanie Becker
Céline Bossard
Marie Parrens
Olivier Casasnovas
Victoria Cacheux
Caroline Régny
Vincent Camus
Marie-Hélène Delfau-Larue
Michel Meignan
Laurence de Leval
Philippe Gaulard
Corinne Haioun
References
PubMed