Amandeep Salhotra, MD
Amandeep Salhotra, MD, Associate Professor of Leukemia at City of Hope, in California, said this study should form the basis for a prospective phase III study in which older patients with AML (60–75 years) should have equal chance at randomization to either arm to remove bias on the part of treating physicians.
“Data on induction mortality and comorbidity (in both arms) will be important to interpret results, as an overall survival benefit is seen in the CPX-351 arm without improvement in the rates of complete response or relapse-free survival,” Dr. Salhotra said in an interview with The ASCO Post. “It’s possible that multiple comorbidities in patients given a hypomethylating agent plus venetoclax may have led to more induction deaths and inferior overall survival.”
Dr. Salhotra also noted that the group given a hypomethylating agent plus venetoclax had a higher proportion of high-risk patients (older age, ELN risk, and molecular markers) yet performed similarly to the CPX-351 arm in terms of overall survival in those aged 60 to 75.
The higher rates of hematopoietic cell transplantation (HCT) in the CPX-351 arm are also interesting, added Dr. Salhotra. These higher rates may be related to an upfront selection bias, with healthier and fit patients receiving CPX-351 rather than a hypomethylating agent plus venetoclax and subsequently moving to curative allogeneic HCT.
“In a phase III trial of CPX-351 vs 7 + 3 cytarabine and daunorubicin chemotherapy,1 HCT outcomes were also better in the CPX-351 arm,” Dr. Salhotra said. “It will be interesting to see how patients performed in both arms after HCT in this study.”
A Retrospective Study in Secondary AML
Finally, Dr. Salhotra referenced a retrospective study conducted at City of Hope. It analyzed outcomes following treatment with either CPX-351 or a hypomethylating agent plus venetoclax in secondary AML.2 The study of 50 patients (n = 20 given CPX-351; n = 30 given a hypomethylating agent plus venetoclax) showed similar rates of overall survival in both arms. However, complete response rates were better with a hypomethylating agent plus venetoclax. Higher rates of measurable residual disease were also observed in both arms in this retrospective study than in the study by Grenet et al.
“Patients who received allogeneic HCT did well in both groups, which shows that an overall survival benefit can be seen as long as patients get to allogeneic HCT,” noted Dr. Salhotra.
DISCLOSURE: Dr. Salhotra reported no conflicts of interest.
REFERENCES
1. Lancet JE, Uy GL, Newell LF, et al: CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol 8:e481-e491, 2021.
2. Salhotra A, Aribi A, Ngo D, et al: Outcome of secondary acute myeloid leukemia treated with hypomethylating agent plus venetoclax or liposomal daunorubicin-cytarabine (CPX-351). Am J Hematol 96:E196-E200, 2021.
