March 17, 2019
2 min read

Lenalidomide, azacitidine regimen safe, active in relapsed AML after transplant

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The combination of lenalidomide and azacitidine appeared safe and demonstrated clinical activity in patients with relapsed acute myeloid leukemia or myelodysplastic syndrome following allogeneic hematopoietic stem cell transplantation, according to results of a prospective trial published in Journal of Clinical Oncology.

“The demonstration that high doses of [lenalidomide], in combination with [azacitidine], exert significant antileukemic activity with modest toxicity in patients who relapse after [allogeneic HSCT] identifies a potentially important new salvage strategy in patients who relapse post-transplantation,” Charles Craddock, MD, director of the blood and marrow transplant unit at Queen Elizabeth Hospital in Birmingham, U.K., and colleagues wrote. “Intensive chemotherapy is often ineffective in this setting and associated with substantial toxicity.”

Relapse is a major cause of treatment failure among patients who receive allogenic HSCT for AML or myelodysplastic syndrome, and salvage treatment options are limited, researchers noted.

Lenalidomide (Revlimid, Celgene) is known to have significant antitumor effects in patients who relapse after allogeneic HSCT, but is associated with high rates of graft-versus-host disease.

Azacitidine, a DNA methyltransferase inhibitor, also has shown antileukemic activity in AML, and it has the ability to hasten reconstitution of T-regulatory cells after transplantation in murine models, leading to reduced risk for GVHD.

Researchers evaluated the tolerability and effectiveness of the combination in a prospective, phase 1, dose-finding trial that included 29 patients (mean age, 54 years; range, 18-73) who relapsed after allogenic HSCT for AML (n = 24) or myelodysplastic syndrome (n = 5). Most of the patients (76%) had prior acute GVHD.

Patients received 75 mg/m2 azacitidine for 7 days followed by escalating doses of lenalidomide (5 mg to 25 mg) on days 10 to 30.

Researchers determined the maximum tolerated dose of lenalidomide, in combination with azacitidine, as 25 mg per day.

Among 15 patients who received at least three cycles of treatment, seven (one with myelodysplastic syndrome and six with AML) had a major clinical response, including three complete responses, three complete responses with incomplete blood count recovery and one partial response. Researchers observed no increase in CD3+ T-cell frequency in peripheral blood.

Results showed median OS of 27 months for patients who responded to the treatment and 10 months for patients who did not respond (P = .004).

Overall, three patients developed grade 2 to 4 GVHD, however, none of those cases led to death.

“Our data establish a potentially important role for a [lenalidomide and azacitidine] combination as salvage therapy in patients with relapsed AML post-allograft and support a randomized comparison of this novel regimen with intensive chemotherapy in this area of major unmet need,” Craddock and colleagues wrote. “Alternatively, combined [lenalidomide and azacitidine] therapy could be administered either as maintenance therapy or, because of the requirement for at least three cycles of therapy to maximize response, pre-emptively in patients with evidence of measurable residual disease.” – by John DeRosier

Disclosures: Craddock reports honoraria from AbbVie, Celgene, Janssen, Jazz Pharmaceuticals and Pfizer; speaker’s fees from Celgene; research funding from Celgene and Jazz Pharmaceuticals; and travel expenses from Celgene and Jazz Pharmaceuticals. Please see the study for all other authors’ relevant financial disclosures.