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Azacitidine, lenalidomide treatment appears safe for myelodysplastic syndrome, AML
A sequential treatment combination of lenalidomide and azacitidine appeared active in and safe for patients with high-risk myelodysplastic syndrome or acute myeloid leukemia, according to study results.
Azacitidine is a hypomethylating agent that is part of standard care for patients with myelodysplastic syndrome. However, responses to the drug have only been temporary, and after the initial treatment fails, the outcomes are poor, according to the study background.
Mikkael A. Sekeres
Guillermo Garcia-Manero, MD, a professor of medicine and chief of the section of myelodysplastic syndrome in the department of leukemia at The University of Texas MD Anderson Cancer Center, and colleagues conducted a single-arm, two-phase study, assessing the addition of lenalidomide (Revlimid, Celgene) to azacitidine in the treatment of high-risk myelodysplastic syndrome and AML.
In phase 1, 28 patients with relapsed or refractory AML or myelodysplastic syndrome with bone marrow blasts of more than 10% received 75 mg/m² azacitidine once daily for the first 5 days of each 28-day cycle. Patients then received lenalidomide for 5 or 10 days starting on day 6. The primary objective for this phase of the study was to establish the maximum tolerated dose.
Although one patient died unexpectedly in phase 1 at the highest dose level, six more patients were recruited with no serious adverse events, and no dose-limiting toxic effects were noted. After the first phase, researchers established the maximum tolerated dose of lenalidomide as 50 mg daily for 10 days.
Phase 2 included 60 patients, and inclusion criteria was adjusted to include patients with less than 30% blasts. OS served as the primary endpoint.
Researchers observed a high rate of myelosuppression and myelosuppression-related toxic effects in the first 20 patients treated in phase 2. This led to an amended lenalidomide dose of 25 mg per day for 5 days.
Median OS was 75 weeks among the 40 patients in phase 2 who received the adjusted dose of lenalidomide.
Twenty-seven patients experienced grade 3 or grade 4 neutropenic fever, and 18 patients developed grade 3 or grade 4 pneumonia.
Among all 88 patients included in both study phases, 31 (35%) demonstrated a response. They included 15 patients who demonstrated complete response and 16 who demonstrated complete response with incomplete hematologic recovery.
“For combination regimens such as azacitidine plus lenalidomide to become standard, an improvement in durable response and overall survival needs to be shown,” Mikkael A. Sekeres, MD, MS, of the department of hematology and oncology at the Cleveland Clinic, wrote in an accompanying editorial. “[Also,] subgroups who benefit from more intense treatment need to be defined; and investigators need to ensure patients are not prematurely removed from such treatments because of side effects that could be effectively managed.”
Disclosure: Celgene provided funding for the study. The researchers report no relevant financial disclosures. Sekeres reports an advisory board role with Celgene.