For older patients with acute myeloid leukemia (AML), front-line treatment with liposomal daunorubicin/cytarabine (CPX-351) appears to be equivalent to treatment with a hypomethylating agent plus venetoclax, according to data presented at the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition.1
In patients between the ages of 60 and 75, results of the multicenter retrospective study showed no significant difference in response rate or median overall survival between those receiving CPX-351 or a hypomethylating agent plus venetoclax. Subgroup analysis of these older patients, however, found better overall survival with CPX-351 in patients with TP53-mutated AML.
“Despite more than double the rate of transplantation in the CPX-351 group, we found no significant difference in overall survival between groups among those aged 60 to 75.”— Justin Grenet, MD
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“Right now, our data suggest there is a group of older patients with AML for whom these two treatments may be equivalent,” said lead study author Justin Grenet, MD, an internal medicine resident at New York Presbyterian/Weill Cornell Medical Center. “We are hopeful that our comorbidity analysis will further clarify why certain patients were receiving each treatment and provide a better sense of which patients would benefit from each regimen.”
Limited Treatment Options
As Dr. Grenet explained, the treatment of older adults with AML has been characterized by limited treatment options and poor outcomes historically. In the past 5 years, however, several new therapies have entered the market and transformed this treatment landscape. Two of these therapies, CPX-351 and a hypomethylating agent plus venetoclax, have shown promise in older patients with AML, with both therapies demonstrating improved overall survival and approved by the U.S. Food and Drug Administration.
CPX-351, an intensive chemotherapy for older, fit patients with AML, is approved for secondary and therapy-related AML, whereas a hypomethylating agent plus venetoclax, a relatively lower-intensity treatment, has been approved for patients older than 75 or patients younger than 75 who are ineligible for intensive chemotherapy. The regimen of a hypomethylating agent plus venetoclax is also being used to treat biologically adverse diseases such as TP53-mutated AML regardless of patients’ fitness.
“Despite approval for different subsets of patients with AML, the two regimens have been increasingly used in similar patient cohorts, given the significant challenges of determining fitness,” added Dr. Grenet.
To analyze the characteristics and outcomes of patients with AML receiving either CPX-351 or a hypomethylating agent plus venetoclax as front-line therapy, Dr. Grenet and colleagues conducted a multicenter retrospective chart review; it drew data from four large U.S academic medical centers (Weill Cornell, Northwestern, Moffitt, Memorial Sloan Kettering). Response was determined using the 2017 European LeukemiaNet (ELN) guidelines.
The study included 211 patients in the CPX-351 group and 226 patients in the group given a hypomethylating agent plus venetoclax. Primary outcomes of interest included response rate (complete response plus complete response with incomplete blood count recovery), relapse-free survival, and overall survival. Analyses were conducted for the overall population and, more importantly, among those between the ages of 60 and 75.
“We chose this age group because it’s where the most overlap was seen between the two treatment groups,” said Dr. Grenet. He noted that patients younger than 60 primarily received CPX-351, whereas those older than 75 primarily received a hypomethylating agent plus venetoclax.
Subgroup analyses included TP53 mutation status, adverse ELN risk, prior myeloid malignancy, and prior therapy with a hypomethylating agent.
Improved Outcomes Among Patients With TP53-Positive Disease
The 60-to-75-year-old group included 152 patients who received CPX-351 and 180 patients who received a hypomethylating agent plus venetoclax. Analysis showed a higher median age among those receiving a hypomethylating agent plus venetoclax vs CPX-351 (70.3 vs 68.5 years). The rate of adverse events and the frequency of TP53-mutated AML were also higher in the venetoclax group. There were no apparent differences in the rate of prior myeloid malignancy or prior therapy with a hypomethylating agent.
Researchers found no difference in response rates among those between the ages of 60 and 75, but the rate of transplantation was more than twice as high in the CPX-351 group (48%) compared with the group given a hypomethylating agent plus venetoclax (19%). “Despite more than double the rate of transplantation in the CPX-351 group, we found no significant difference in overall survival between groups among those aged 60 to 75,” Dr. Grenet said.
“The only significant difference [in this age group] was a higher median overall survival seen in TP53-positive patients who received CPX-351,” said Dr. Grenet. “However, there were significantly lower rates of transplantation in the group given a hypomethylating agent plus venetoclax.”
In addition, among those aged 60 to 75, no difference in survival was observed between the two treatment arms after achieving a complete response. In addition, there was no difference in posttransplant survival.
According to Dr. Grenet, the limitations of the study include the inherent biases of retrospective chart reviews, the lack of measurable residual disease data, and small numbers limiting the posttransplant analysis. Further investigations of preinduction and postinduction fitness scores are pending.
DISCLOSURE: Dr. Grenet reported no conflicts of interest.
1. Grenet J, Jain AG, Burkart M, et al: Comparing outcomes between liposomal daunorubicin/cytarabine (CPX-351) and HMA + venetoclax as frontline therapy in acute myeloid leukemia. 2021 ASH Annual Meeting & Exposition. Abstract 32. Presented December 11, 2021.
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 ...