Positive findings from two clinical trials have been published for the immunomodulatory agent lenalidomide in patients with heavily pretreated mantle cell lymphoma, and in adults with T-cell leukaemia-lymphoma or peripheral T-cell lymphoma.
The results of the phase II MCL-002 (SPRINT) study suggest that, compared with an investigator's choice of treatment, lenalidomide 25 mg/day on days 1-21 of a 28-day cycle significantly improved progression-free survival (PFS) in patients with relapsed or refractory mantle cell lymphoma who were ineligible for intensive chemotherapy or stem cell transplantation.
After a median of 15.9 months, the 170 lenalidomide-treated patients had a median PFS of 8.7 months compared with 5.2 months in the 84 patients who were treated with single-agent rituximab, gemcitabine, fludarabine, chlorambucil or cytarabine, giving a hazard ratio (HR) of 0.61.
As reported in The Lancet Oncology, lenalidomide-treated patients were significantly more likely than those given the investigator's choice to achieve an objective response (40 vs 11%), and there were trends towards a longer duration of response (16.1 vs 10.4 months) and overall survival (27.9 vs 21.2 months).
Marek Trnĕný, from Charles University Hospital in Prague, Czech Republic, and co-authors note that patients given lenalidomide maintained their global quality of life status despite a longer duration of treatment than with an investigator's choice of treatment.
The safety profile was "consistent" with previous reports for lenalidomide and although there was a higher rate of adverse events than with investigator's choice, this may in part be attributed to the longer duration of treatment, the researchers say. Grade 3 and 4 side effects included neutropenia (44 vs 34%), thrombocytopenia (18 vs 28%), leucopenia (8 vs 11%) and anaemia (8 vs 7%).
The phase I ATLL-001 dose-escalation study in Japanese patients, published in The Lancet Haematology, successfully determined a dose and schedule for lenalidomide based on results for nine participants with relapsed adult T-cell leukaemia-lymphoma and four with peripheral T-cell lymphoma, treated for a median of 2.2 months.
The maximum tolerated dose was 25 mg/day given on a continuous basis, with grade 3 or more severe events at all doses including neutropenia (62%), lymphopenia (54%) and thrombocytopenia (31%). Although 62% of patients experienced a serious adverse event, thrombocytopenia was the only such effect to occur in more than one patient, affecting 23% in all.
Three patients with adult T-cell leukaemia-lymphoma had a response in the peripheral blood, including two complete responses. A further four patients met some criteria for a partial response in target lesions or peripheral blood.
"Pharmacokinetic, safety, and preliminary efficacy results from this phase 1 study of single-agent lenalidomide provide the rationale for and establish the dosage used in the phase 2 ATLL-002 study of a larger number of patients with relapsed or recurrent adult T-cell leukaemia-lymphoma", say Michinori Ogura, from Tokai Central Hospital in Kakamigahara, Japan, and co-authors.
Noting that there is great unmet need for patients with relapsed adult T-cell leukaemia-lymphoma, the team writes that this first report for lenalidomide in this population suggests the agent may have a "positive benefit-risk ratio, with the potential for becoming a treatment option".
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