Phase I study of continuous high dosing lenalidomide in patients with acute myeloid leukemia

Data from the phase I dose escalation study (NCT00839059) evaluating the safety and efficacy of single-agent continuous high dose lenalidomide in patients with relapsed or refractory (R/R) or older patients with newly diagnosed acute myeloid leukemia (AML) who are not suitable for other treatment options, were reported in Haematologica by researchers from the University of Ulm, Ulm, Germany.

Fourteen patients (median age = 71.5 years, range: 35–83) were enrolled between March 2009 – June 2010. Twelve patients with R/R (n = 8) or newly diagnosed (n = 4) AML were treated with a starting dose of 25 mg lenalidomide per day as a continuous treatment until complete remission (CR) or dose-limiting toxicity (DLT) on day 56. Five patients received 25 mg/day lenalidomide with no DLT. Seven patients received 50 mg/day lenalidomide.

Key findings:

Safety

• DLT of grade III polyneuropathy occurred in two patients receiving 50 mg/day lenalidomide
• No cytokine release syndrome was observed in patients
• Ten patients had serious adverse events that were not manageable in an out-patient setting
• 30-day mortality rate: 42% (5/12)
• 60-day mortality rate: 50% (6/12)

On day 22 (first evaluation response time point), seven patients were evaluable for response. Five patients did not continue treatment on trial due to rapid progressive disease (n = 3) or severe infectious complications (n = 2).

Response evaluation

• No patient treated in this study achieved CR or partial response
• A decrease in bone marrow blasts from 40% to 15% occurred in one patient

In summary, “high-dose lenalidomide in relapsed or refractory as well as elderly treatment naïve AML is not feasible and has a limited efficacy as monotherapy”.