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Azacitidine possibly more than a palliative option for leukemia subtype
ATLANTA — The use of azacitidine in an older patient population that tends to experience poor outcomes with intensive chemotherapy appeared to yield effective remissions in acute myeloid leukemia, according to findings presented at the ASH Annual Meeting and Exposition.
Azacitidine (Vidaza, Celgene) was also well tolerated, according to study results.
“This therapy is often considered to be palliative rather than potentially curative in patients,” Michael R. Grunwald, MD, of the Levine Cancer Institute, told HemOnc Today. “The study showed that some patients were able to improve enough to become candidates for a potentially curative therapy with allogeneic transplant.”
Grunwald said that azacitidine has typically been considered a standard treatment for older and unfit patients with AML who are thought to be unfit to receive standard induction chemotherapy with cytarabine and anthracycline. Previously, research in 2009 had demonstrated that patients who achieved complete remission with frontline azacitidine may improve to become candidates for reduced intensity conditioning allogeneic hematopoietic cell transplantation.
However, as Grunwald said, there has been very limited data available regarding the use of azacitidine as a bridge to transplant in AML.
The aim of the study was to evaluate remission status and survival outcomes in patients who were treated with azacitidine in the front-line setting and underwent hematopoietic cell transplantation.
Grunwald and colleagues analyzed the results from 27 patients (median age 70.5 years; 60-77) diagnosed with AML between December 2015 and October 2016 who were originally deemed unfit for intensive chemotherapy. Patients then received front-line azacitidine treatment as a possible bridge to HCT.
Ten patients (median age 70.5 years, 60-77; male, 80%) proceeded directly to transplant, and the remaining patients did not undergo transplant.
Three of the patients who successfully bridged to transplant were considered favorable risk by NCCN guidelines. Three were considered intermediate risk, three were poor risk and one had an unknown risk status.
Each patient received 75 mg/m2 of azacitidine administered intravenously on days 1 through 7 of a 28-day cycle, for a median of 6 cycles (range 4-11), without delays or dose reductions. Four patients received other chemotherapeutic agents concomitantly with azacitidine.
During treatment, five patients achieved a complete remission and four patients achieved a complete remission with incomplete hematologic recovery.
Each patient maintained remission statuses following therapy until immediately prior to transplant.
Nine patients underwent haploidentical peripheral blood HCT, and one underwent matched related peripheral blood HCT. All patients received a reduced intensity conditioning regimen consisting of fludarabine, cyclophosphamide, and total body irradiation as well as post-transplant cyclophosphamide.
Grunwald acknowledged that one patient who died from septic shock early during his transplant admission was included in survival analyses.
Three patients achieved CR at their first disease assessment following transplant. Three obtained a CR with incomplete platelet recovery, two exhibited CR with incomplete hematologic recovery and one patient relapsed.
Median follow-up from diagnosis was 14.5 months (9.6-19.7).
One-year OS rate was 86% and the 1-year leukemia-free survival rate was 75%, according to Kaplan-Meier analyses.
Median OS was 19.2 months (95% CI; 12-NA) and a median LFS was not reached during the study.
Grunwald noted that the study population was rather small and that the goal is to look at the use of azacitidine in the front-line setting as a bridge to transplant in a larger prospective study.
“While our project consists of a small group of patients, I think that it shows that it is possible to bridge patients to transplant with a hypomethylating agent and that this is not necessarily only a palliative treatment,” Grunwald said. “One further corollary of that is that we might be able to get more patients to transplant if we treat marginally fit patients and unfit patients relatively gently at the outset and then save their reserve or allow them to improve prior to allogeneic transplantation.” – by Ryan McDonald
Reference:
Grunwald MR, et al. Poster 3864. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta.
Lubbert M, et al. Bone Marrow Transplant. 2009;doi:10.1038/bmt.2009.64.
Disclosures: Grunwald reports no relevant financial disclosures.