Lenalidomide in Adult T-Cell Leukemia/Lymphoma

Adult T-cell lymphoma/leukemia (ATLL), a rare malignancy caused by infection with the retrovirus human T-lymphotropic virus type 1, is an aggressive T-cell lymphoma subtype that has one of the poorest prognoses of any non-Hodgkin lymphoma. In a large retrospective analysis, patients with ATLL had a 5-year failure-free and overall survival of only 12% and 14%, respectively.1 The disease is typically subdivided into four clinical presentations: smoldering (generally indolent), chronic (variable course), lymphoma, and acute (both aggressive), with the poorest prognoses seen among those with poor risk or relapsed chronic, lymphoma, and acute subtypes.2 Although most common in human T-lymphotropic virus type 1–endemic regions such as Japan, the Caribbean, and sub-Saharan Africa, ATLL constitutes 1% to 2% of T-cell lymphomas in the United States and Europe.1

The treatment of ATLL remains a challenge. Prospective clinical trials from Japan, using regimens such as cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or an aggressive combination chemotherapy, vincristine, cyclophosphamide, doxorubicin, and prednisone; doxorubicin, ranimustine, and prednisone; vindesine, etoposide, carboplatin, and prednisone (VCAP-AMP-VECP), for patients with the chronic, lymphoma, and acute subtypes, showed median overall survival rates from 8.3 to 10.6 months.3,4 These initial therapies provide response rates of approximately 70%, with a complete response rate of approximately 30%.4 However, nearly 90% of patients relapse, on average within months of completing therapy, and currently consolidation of first remission with allogeneic stem-cell transplantation is strongly considered.5 For patients with relapsed/refractory ATLL, the prognosis is even poorer.

In addition to the poor prognosis, patients with ATLL have either been underrepresented or excluded from many trials of novel agents more recently tested in T-cell lymphoma. In the development of pralatrexate, there were a total of three subjects in the pivotal phase I and phase II trials. Those with ATLL were excluded from the registration studies of romidepsin, belinostat, and alisertib. In the phase II Southwest Oncology Group trial of alisertib, four patients with ATLL were treated and one of them responded.6 There is otherwise only anecdotal use reported with brentuximab vedotin and romidepsin.7,8 Although not excluded from the phase II study of brentuximab vedotin in T-cell lymphoma, there were no patients with ATLL enrolled in this trial. Of note, two patients were treated in the phase I/II study of brentuximab vedotin with CHOP without vincristine (CHP).9 In a retrospective analysis, Bazarbachi et al10 demonstrated that patients with the acute and lymphoma subtypes of ATLL had median overall survival of 9 months with initial therapy with interferon and zidovudine. However, when this strategy was evaluated as a maintenance approach after combination chemotherapy, there was little to no evidence of durable benefit.11 In 2015, mogamulizimab, an anti-CCR4 antibody, was approved in Japan on the basis of a 50% response rate and median progression-free survival of 5.2 months in 27 patients with relapsed ATLL.12 (...)

Journal of Clinical Oncology , éditorial en libre accès, 2016

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