Lenalidomide trials show potential for expanding lymphoma, leukaemia indications

By Lynda Williams, Senior medwireNews Reporter

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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