Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002

Abstract

Purpose Few treatment options exist for adult T-cell leukemia/lymphoma (ATL), and the prognosis for this disease is poor. A phase I study of lenalidomide demonstrated preliminary antitumor activity in patients with relapsed ATL. The current phase II study evaluated the efficacy and safety of lenalidomide monotherapy in patients with relapsed or recurrent ATL. Patients and Methods Patients 20 years of age or older with acute, lymphoma, or unfavorable chronic subtype ATL, who had received one or more prior anti-ATL systemic chemotherapy and achieved stable disease or better on their last anti-ATL therapy with subsequent relapse or recurrence, were eligible. Patients received oral lenalidomide 25 mg/d continuously until disease progression or unacceptable toxicity. The primary end point was overall response rate; secondary end points included safety, tumor control rate (stable disease or better), time to response, duration of response, time to progression, progression-free survival, and overall survival. Results Objective responses were noted in 11 of 26 patients (overall response rate, 42%; 95% CI, 23% to 63%), including four complete responses and one unconfirmed complete response. The tumor control rate was 73%. The median time to response and duration of response were 1.9 months and not estimable, respectively, and the median time to progression was 3.8 months. The median progression-free survival and overall survival were 3.8 and 20.3 months, respectively. The most frequent grade ≥ 3 adverse events were neutropenia (65%), leukopenia (38%), lymphopenia (38%), and thrombocytopenia (23%), which were all manageable and reversible. Conclusion Lenalidomide demonstrated clinically meaningful antitumor activity and an acceptable toxicity profile in patients with relapsed or recurrent aggressive ATL, hinting at its potential to become a treatment option. Further investigations of lenalidomide in ATL and other mature T-cell neoplasms are warranted.

Epidemiological and clinical features of adult T‐cell leukemia–lymphoma in Japan, 2010–2011: A nationwide survey

“…Recently, for aggressive ATL, several promising therapeutic antibodies, such as anti‐CC chemokine receptor 4 mAb and an anti‐CD52 antibody, have been introduced and have achieved significant reduction of ATL cells. Furthermore, lenalidomide, an immune‐modulatory agent, has been introduced for relapsed aggressive ATL patients . In Europe and America, an antiviral therapy with a combination of zidovudine (AZT) and interferon‐α has been introduced for ATL patients with leukemic manifestation .…”

The outcome and characteristics of patients with relapsed adult T cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation

“…To enhance the GvATLL effect and to avoid the toxicity of GVHD, new molecular target therapies for ATLL are being investigated. Two promising new agents are mogamulizumab and lenalidomide . In particular, considering the increasing number of cord blood transplantations for patients with ATLL who cannot receive DLI, these agents might enhance GvATLL by immunomodulation after transplantation.…”

Prognostic index for chronic- and smoldering-type adult T-cell leukemia-lymphoma

“…Regarding the novel agents, the findings of a phase 2 study on lenalidomide showed a promising overall response rate and survival in relapsed and recurrent patients with aggressive ATL. 8 Furthermore, several clinical trials on novel agents such as the histone deacetylase inhibitors, alemtuzumab, brentuximab vedotin, nivolumab, and an EZH1/ 2 dual inhibitor are currently in progress. This novel prognostic model would be useful for risk-adapted therapeutic intervention in the future.…”

“…A phase 2 study of lenalidomide in relapsed or recurrent patients with aggressive ATL showed an overall response rate, median progression-free survival, and MST of 42%, 3.8 months, and 20.3 months, respectively. 8 In terms of antiviral therapies, the effect of a combination of IFN/AZT on patients with ATL was reported in 1995 for the first time. 9,10 Gill et al reported the overall response rate of 58% and MST of 3 months in 19 aggressive ATLs, including 12 patients previously treated.…”