Glasdegib in combination with low-dose Cytarabine for the outpatient treatment of relapsed or refractory acute myeloid leukemia in unfit patients

Abstract

We retrospectively collected clinical data on 31 relapsed or refractory acute myeloid leukemia (R/R AML) patients who were treated with outpatient glasdegib and low-dose Cytarabine (LDAraC) at our institution. The median age was 67 years (45–86). The median Eastern Cooperative Oncology Group performance status was 2 (1–3). The patients had previously received a median number of 2 (1–4) treatment lines, 61% (19/31) had been treated with intensive chemotherapy, 29% (9/31) had relapsed after allogeneic stem cell transplantation, and 45% (14/31) had had venetoclax exposure. Adverse cytogenetics were identified in 45% (14/31) of the cases. The CR + CRp rate was 21% (6/29) among evaluable patients. The median overall survival was 3.9 months for all patients. Different median overall survival times were observed in responders, patients achieving stable disease and those diagnosed with progressive disease: not reached vs 3.9 months vs 0.8 months, respectively ( p < 0.001). The most common adverse events were pneumonia (29%, 9/31), sepsis (23%, 7/31), and febrile neutropenia (16%, 5/31). Glasdegib + LDAraC is a fairly safe, non-intensive, outpatient regimen inducing complete remission and resulting in prolonged survival in some R/R AML patients.

Acute myeloid leukemia: 2023 update on diagnosis, risk‐stratification, and management

“…Although no direct comparison was performed, due to the similarity of the populations evaluated in the VIALE‐A and VIALE‐C trials and with better results shown with venetoclax combination, glasdegib is not widely used in patients with ND AML deemed unfit for intensive chemotherapy. The efficacy of glasdegib with LDAC in the R/R setting was evaluated in a small retrospective study that demonstrated composite CR (CR + CRp) rates of 21% with a median OS of 3.9 months 154 . Thus, the role of glasdegib in the treatment algorithm for newly diagnosed older adult setting is not yet determined, as other alternatives seem more appealing.…”

“…The efficacy of glasdegib with LDAC in the R/R setting was evaluated in a small retrospective study that demonstrated composite CR (CR + CRp) rates of 21% with a median OS of 3.9 months. 154 Thus, the role of glasdegib in the treatment algorithm for newly diagnosed older adult setting is not yet determined, as other alternatives seem more appealing.…”

Prevention and Treatment of Acute Myeloid Leukemia Relapse after Hematopoietic Stem Cell Transplantation: The State of the Art and Future Perspectives

“…Zucenka et al have reported the use of glasdegib combined with low-dose cytarabine in 31 patients affected by R/R AML, 9 (29%) of whom relapsing early after HSCT. The median overall survival was 10.4 months and interestingly, an univariate analysis revealed that previous HSCT and venetoclax exposure did not significantly influence the survival [ 185 ].…”

The Elephant in The Room: AML Relapse Post Allogeneic Hematopoietic Cell Transplantation

“…Glasdegib was tested in combination with low dose cytarabine in the frontline treatment of AML in patients who are ineligibile for intensive chemotherapy (53). It was used in the R/R setting with modest efficacy (54). Other novel agents include MCL1 inhibitors, MDM2 inhibitors especially in combination with venetoclax (55,56).…”