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Lenalidomide shows promise in rare leukemia, lymphoma subtypes
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Single-agent lenalidomide exhibited favorable antitumor activity and acceptable toxicity in patients with aggressive relapsed or recurrent adult T-cell leukemia/lymphoma, according to phase 2 study results.
Patients with relapsed or recurrent adult T-cell leukemia/lymphoma (ATL) experience generally poor outcomes due to a lack of effective therapeutic options. A phase 1 study of continuous oral lenalidomide (Revlimid, Celgene) demonstrated antitumor activity at a maximum tolerated dose of 25 mg per day.
Takashi Ishida, MD, PhD, of the department of medical oncology and immunology at Nagoya City University Graduate School of Medical Sciences in Japan, and colleagues sought to determine the clinical efficacy and safety profile of lenalidomide monotherapy in this patient population.
The study included data from 26 patients (median age, 68.5 years; range, 53-81; 54% men) who experienced relapse or recurrence after previously achieving stable disease. The researchers assigned patients to daily lenalidomide at the maximum tolerated dose until disease progression or unacceptable toxicity.
The study population included three disease subtypes: acute ATL (n = 15), lymphoma (n = 7) and unfavorable chronic ATL (n = 4).
Overall response rate served as the primary outcome measure. Secondary outcome measures included safety, tumor control rate, duration of response, time to progression, PFS and OS.
Median follow-up was 3.9 months.
Eleven patients achieved an objective response, which corresponded to an ORR of 42% (95% CI, 23-63). Four patients achieved a complete response and one patient achieved an unconfirmed complete response.
Thirty-three percent (n = 5) of patients with acute ATL responded, as did 57% (n = 4) of patients with lymphoma and 50% (n = 2) of patients with chronic unfavorable ATL.
The cohort had a tumor control rate — defined as stable disease or better — of 73%, with a median time to response of 1.9 months (range, 1.8-3.7) and time to progression of 3.8 months (range, 1.9-not reached).
The median duration of response was not reached; the mean duration of response was 5.2 months (range, 0-16.6).
The cohort had a median PFS of 3.8 months (95% CI, 1.9-not reached) and median OS of 20.3 months (95% CI, 9.1-not reached).
Five patients remained on study at the time of data cutoff. The remaining patients discontinued treatment due to disease progression (n = 13), adverse events (n = 6) or other reasons (n = 2).
Commonly observed hematologic adverse events included thrombocytopenia (77%), neutropenia (73%), lymphopenia (69%) and anemia (54%).
Nine patients experienced serious adverse events, two of whom experienced thrombocytopenia — the only serious adverse event observed in more than one. All but two serious adverse events resolved; the researchers reported an ongoing case of thrombocytopenia and a case of acute hepatic failure that appeared to be improving at the end of follow-up.
The researchers acknowledged study limitations, including the small sample size and inclusion of patients with multiple disease subtypes. Further, enrolled patients received disparate prior therapies, which may have influenced outcomes.
“On the basis of these promising results, further investigations of lenalidomide in ATL and other T-cell neoplasms are warranted,” Ishida and colleagues wrote.
The degree to which these study findings can be translated to real-world practice remains unclear, Neha Mehta-Shah, MD, assistant professor of medicine at Washington University School of Medicine, and Steven M. Horwitz, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, wrote in a related editorial.
“Although we are excited about the reported activity, our enthusiasm is a bit tempered by concerns as to how applicable these results may be to the typical population of patients with relapsed disease we see in the United States,” Mehta-Shah and Horwitz wrote. “There has been no formal comparison between patients in Japan and elsewhere, but in a New York City experience, the median survival for all patients (regardless of subtype) was 24 weeks from diagnosis. On the basis of the eligibility criteria, many of our typically symptomatic and frequently treatment-refractory patients would not have been candidates for this study. The accompanying study required a 4-week washout period, as well as maintenance of at least stable disease from the antecedent therapy.”
These results may be most important as a form of hypothesis-generating research.
“Although the response rate in the Japanese population may not be recapitulated in aggressive refractory disease, Ishida and colleagues provide evidence of an important option for patients with ATL and lay important groundwork to build upon,” Mehta-Shah and Horwitz wrote. – by Cameron Kelsall
Disclosure: Celgene K.K. provided funding for this study. Ishida reports honoraria and institutional research funding from Bayer Pharma AG, Celgene K.K. and Kyowa Hakko Kirin. Please see the full study for a list of all other researchers’ relevant financial disclosures. Horwitz reports research funding and travel expenses from, as well as consultant roles with, multiple pharmaceutical companies, including Celgene. Mehta-Shah reports no relevant financial disclosures.
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