Five-year follow-up data from the phase 3 CLTR0310-301 clinical trial shows continued OS benefit with the novel agent CPX-351 in acute myeloid leukemia subgroups.
Treatment with CPX-351 (Vyxeos) in older adults with newly diagnosed high-risk or secondary acute myeloid leukemia (AML) who achieved complete response (CR) or CR with incomplete hematologic recovery (CRi) or who underwent hematopoietic stem cell transplant (HCT) , demonstrated improvement in overall survival (OS) when compared with the standard 7 + 3 chemotherapy, according to 5-year follow-up data from the phase 3 CLTR0310-301 trial (NCT01696084).1
Results from the trial were presented at the 2021 Transplant and Cellular Therapy Meetings of ASTCT and CIBMTR. In it, patients were randomized 1:1 to CPX-351 (n = 153)—a dual-drug encapsulation of cytarabine/daunorubicin—or the 7 + 3 regimen (n = 156), defined as the combination of cytarabine and daunorubicin.
“The longer OS with CPX-351 versus 7 + 3 in patients who achieved CR or CRi and in those who underwent HCT suggests potentially deeper responses may be achieved with CPX-351 treatment,” the authors of the poster, who were led by Jorge E. Cortes, MD, wrote in their conclusion. “These data support the prior evidence that CPX-351 has the ability to produce and contribute to long-term remission and survival in older patients with newly diagnosed high-risk/secondary AML.”
In the total cohort, patients receiving CPX-351 experienced a median OS of 9.33 month (95% CI, 6.37-11.86) compared with 5.95 months (95% CI, 4.99-7.75) in patients who were treated with the standard comparator (HR, 0.70; 95% CI, 0.55-0.91). OS rates at 3 (21% vs 9%) and 5 years (18% vs 8%) were both superior in the CPX-351 arm.
HCT was received by 53 patients from the CPX-351 arm and 39 patients from the 7 + 3 arm; the median OS landmarked from the date of HCT in these patients was not reached versus 10.25 months, respectively (HR, 0.51; 95% CI, 0.28-0.90). The corresponding rates of survival at 3 years were 56% and 23%.
In all patients achieving a CR or CRi in the CPX-351 (n = 73) and the 7 + 3 (n = 52), the median OS was better for those in the experimental arm at 21.72 months versus 10.41 months, respectively (HR, 0.59; 95% CI, 0.39-0.88). Rates of OS at 3 and 5 years in the CPX-351 group were 36% and 30% compared with 23% and 19% with the 7 + 3 regimen. The risk of disease progression or death improved further with CPX-351 in this group when patients subsequently underwent HCT (HR, 0.50; 95% CI, 0.26-0.97).
By age group, the survival advantage of CPX-351 over 7 + 3 was most notable in patients aged 70 to 75 years, with a corresponding median of 8.87 months and 5.62 months (HR, 0.52; 95% CI, 0.34-0.77). Estimated 3- and 5-year survival rates with CPX-351 were 18% and 16%, respectively, versus 0% for both timepoints in patients receiving 7 + 3. Survival advantage was also noted in those ages 60 to 69 years, yet the advantage in the risk of disease progression or death was lower (HR, 0.73; 95% CI, 0.54-0.99).
In the CPX-351 and 7 + 3 arms, there were a total of 124 and 140 deaths, respectively, from progressive leukemia (56% vs 53%) and adverse events (14% each), among other causes. The safety profile of the experimental regimen was generally consistent with the known safety profile of conventional 7 + 3 therapy. All-cause and early mortality rates (30- and 60-day) were lower with CPX-351.
When patients were stratified by ECOG performance status, disease karyotype, and hematologic parameters, OS advantage was found to consistently favor CPX-351. Covariates not found to be associated with OS included sex, hemoglobin levels, percentage of bone marrow blasts, and FLT3-ITD mutation positivity.
Patient characteristics were well balanced between the 2 groups, with a median age of 67 years and a majority of patients being men. AML subtypes in the CPX-351 and 7 + 3 arms were therapy-related AML (20% vs 21%, respectively); AML with antecedent myelodysplastic syndrome (MDS), with (33% vs 35%) or without (14% vs 12%) prior hypomethylating agents; AML with antecedent CMML (7% vs 8%); or de novo AML with MDS karyotype (27% vs 24%).
The indicated study led to the approval of CPX-351 in 2017 for the treatment of adults with newly-diagnosed, therapy-related AML (t-AML) or AML with myelodysplasia-related changes, 2 disease subtypes known for poor outcomes to therapy.2
1. Five-Year Final Results of a Phase 3 Study of CPX-351 Versus 7+3 in Older Adults with Newly Diagnosed High-Risk/Secondary Acute Myeloid Leukemia (AML): Outcomes By Age Subgroup and Among Responders. Presented at: 2021 Transplant and Cellular Therapy Meetings of ASTCT and CIBMTR; February 8-12, 2021. Abstract 135.
2. FDA approves liposome-encapsulated combination of daunorubicin-cytarabine for adults with some types of poor prognosis AML. FDA. August 3, 2017. Accessed February 10, 2021. https://bit.ly/2MRE8cE