Low-Dose Cytarabine Plus Glasdegib in AML
Posted: Monday, August 31, 2020
For patients with acute myeloid leukemia (AML), the addition of the hedgehog pathway inhibitor glasdegib to low-dose cytarabine showed a clinical benefit over low-dose cytarabine alone, including in patients who did not achieve cytologic remission. This post hoc analysis of the phase II BRIGHT AML 1003 trial was published in the Journal of Hematology & Oncology by Michael Heuser, MD, of Hannover Medical School, Germany, and colleagues.
“By targeting leukemic stem cells while sparing normal hematopoiesis, glasdegib + low-dose cytarabine may be an effective agent for improving survival without substantial marrow suppression and attendant cytopenic complications,” concluded the authors.
The study enrolled 116 patients with newly diagnosed and previously untreated AML or high-risk myelodysplastic syndromes who were ineligible for intensive chemotherapy. Patients received oral glasdegib once a day in a 28-day cycle plus low-dose cytarabine subcutaneously twice a day for 10 days every 28 days or low-dose cytarabine alone.
The response rate was higher with cytarabine plus glasdegib than with cytarabine alone, with complete response rates of 19.2% and 2.6%, respectively. The median overall survival was 43.4 months with combination therapy and 42.0 months with cytarabine alone.
For patients who did not achieve a complete response, overall survival was also higher for those who received glasdegib plus cytarabine (5.0 months) compared with cytarabine alone (4.1 months; hazard ratio = 0.63). The 12-month survival probability was 27.3% and 5.7% with the combination and the single therapy. More patients who received glasdegib plus cytarabine achieved a durable recovery of absolute neutrophil count (45.6% vs. 35.5%), hemoglobin (54.4% vs. 38.7%), and platelets (29.8% vs. 9.7%) as well.
The incidence of treatment-related adverse events among patients who did not achieve a complete response did not significantly differ between the two groups. Common short-term adverse events with the combination and single therapies included anemia, febrile neutropenia, pneumonia, thrombocytopenia.
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