番茄社区

SAN DIEGO -- Older patients with high-risk acute myeloid leukemia (AML) lived significantly longer when they received induction therapy with an investigational liposome-encapulated chemotherapy prior to allogeneic stem cell transplant (ASCT), data from a randomized trial showed.

Patients who received conventional induction chemotherapy had a median survival of 10.25 months after ASCT, whereas the median had yet to be reached during follow-up for as long as 30 months in patients who received liposomal cytarabine/daunorubicin (CPX-351). The difference represented a greater than 50% reduction in the survival hazard in favor of induction with CPX-351.

The results added to a previously reported survival benefit of older patients with AML treated with CPX-351, a majority of whom did not undergo ASCT, , of Moffitt Cancer Center in Tampa, Fla., reported here at the American Society of Hematology annual meeting.

"Outcomes after allogeneic transplant in older patients with high-risk AML appear superior in patients treated with CPX-351, including 53% fewer deaths within 100 days of transplant," said Lancet. "These results should be interpreted with caution, given that this was an exploratory analysis of a nonrandomized subgroup."

"CPX-351 may provide a bridge to successful transplant in a poor-risk subgroup of AML patients," he added. "Induction with CPX-351 was associated with lower induction-related morbidity and mortality, which means that patients may be transplanted in better condition. Patients may also attain better disease control, leading to more patients being transplanted in complete remission."

The data suggest that CPX-351 has potential as a bridge to transplant, which could have a major impact on treatment of older patients with high-risk AML, said , of Princess Margaret Hospital and the University of Toronto.

"According to data from the [NCI-sponsored] , a majority of patients over 65 don't get what I would consider definitive therapy, and some of them don't get any therapy at all," Keating told 番茄社区. "This study involved a small unselected group of patients. We need to better define which patients might benefit most from this therapy."

The results with CPX-351 likely apply to younger patients as well, added Keating, who was not involved in the study.

Intensive induction chemotherapy is standard for patients with newly diagnosed AML, although few patients attain a cure with chemotherapy alone. Moreover, patients ages ≥60 have lower remission rates and an increased risk of induction mortality.

As reported , a phase III randomized trial showed significantly better median survival in older patients with AML treated with CPX-351 as compared with conventional 7+3 induction with cytarabine and daunorubicin (9.56 versus 5.95 months, P=0.005). Event-free survival and remission rate also were significantly improved in patients who received CPX-351.

The trial included 309 randomized patients ages 60 to 75. Only patients who achieved complete remission with induction were eligible for ASCT. Treatment with CPX-351 led to a higher rate of complete response (47.7% versus 33.3%).

Lancet reported findings from an exploratory analysis limited to 91 patients who underwent ASCT, 52 in the CPX-351 arm and 39 in the 7+3 arm. Patients in the CPX-351 arm were older (31% ages 70-75 compared with 15% in the 7+3 arm), but otherwise the two groups had similar demographic and clinical characteristics.

The analysis yielded a survival hazard ratio of 0.46 in favor of the CPX-351 group (P=0.0046). A separate analysis yielded a time-dependent Cox hazard ratio for survival of 0.51 for CPX-351 versus 7+3 (95% CI 0.35-0.75, P=0.0007).

Other outcomes also favored treatment with CPX-351. Mortality at 100-days posttransplant was 9.6% for patients in the CPX-351 group and 20.5% in the 7+3 arm. Causes of death within 100 days were all higher in the 7+3 arm, including refractory AML, graft-versus-host disease, renal failure, respiratory failure, multiorgan failure, and septic shock.

Comment