CPX-351 Improves Survival Post Transplant in Older High-Risk Patients With Acute Myeloid Leukemia

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Induction therapy with the experimental chemotherapy called CPX-351—a liposomal formulation of cytarabine and daunorubicin—outperformed standard “7+3” cytarabine plus daunorubicin by extending survival in older high-risk patients with acute myeloid leukemia (AML) who subsequently underwent allogeneic hematopoietic cell transplantation. These were the findings of a subgroup analysis of a large phase III trial.1

Final results of the open-label phase III trial were presented at the 2016 Annual Meeting of ASCO earlier in 2016.2 The study randomized 309 older patients (aged 60–75 years) 1:1 to receive induction therapy with CPX-351 (100 units/m2 on days 1, 3, and 5) or 7+3 (cytarabine at 100 mg/m2/d × 7 days; daunorubicin at 60 mg/m2 on days 1, 2, and 3) from December 2012 to November 2014 at 39 sites in North America. High-risk disease was defined as secondary AML or AML with myelodysplastic syndromes–related cytogenetics.

CPX-351 treatment improved overall survival vs 7+3. Median overall survival was 9.56 months with CPX-351 vs 5.95 months with 7+3—a significant 31% improvement favoring CBX-351 (P = .005). Event-free survival and 60-day mortality also favored CPX-351. No difference was seen between the two arms in the frequency and severity of adverse events.

What sets CPX-351 apart is that the liposomal formulation delivers the two drugs in a synergistic ratio optimized for cell kill. We think that by doing this, we can improve delivery to the cancer cells at the proper ratio.
— Jeffrey E. Lancet, MD

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Based on that trial, lead author Jeffrey E. Lancet, MD, of H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, said: “CPX-351 should become the standard of care for older patients with secondary AML.”

At the 2016 American Society of Hematology (ASH) Annual Meeting & Exposition, Dr. Lancet presented the subgroup analysis of patients originally randomized to induction therapy with either treatment who went on to have allogeneic hematopoietic cell transplantation.

“The subgroup analysis of the original trial showed that CPX-351 achieves superior outcomes in high-risk AML in older patients undergoing transplant. Overall survival is improved. These results should be interpreted with caution, because it is a subgroup analysis of a large randomized trial. But the findings suggest that CPX-351 may provide a bridge to transplant and may provide a better opportunity for disease control prior to transplant in this group of patients,” Dr. Lancet revealed. “We plan to study this further.”

“What sets CPX-351 apart is that the liposomal formulation delivers the two drugs in a synergistic ratio optimized for cell kill. We think that by doing this, we can improve delivery to the cancer cells at the proper ratio,” explained Dr. Lancet.

Details of Subgroup Analysis

The subgroup analysis was based on 91 patients who underwent allogeneic hematopoietic cell transplantation, including 52 patients treated with CPX-351 and 39 patients who received 7+3. Thus, those who received CPX-351 were more likely to go on to transplant. Patients were well matched for baseline and demographic factors, with the exception of a higher percentage of patients over age 70 in the CPX-351 arm (16 [31%] vs 6 [15%], respectively).

New Chemotherapy Delivery Method in AML

  • CPX-351 (a liposomal formulation of daunorubicin and cytarabine) significantly improved overall survival in older high-risk patients undergoing allogeneic hematopoietic cell transplant compared with standard induction therapy with daunorubicin and cytarabine (known as the 7+3 regimen).
  • The results of a subgroup analysis follow on the heels of the original trial, showing that induction therapy with CPX-351 extended survival vs 7+3.
  • CPX-351 may provide a bridge to transplant, allowing older high-risk patients to receive potentially curative therapy.

CPX-351–treated patients were more likely to undergo transplantation while in remission (75% vs 62%, respectively). In the original trial, more patients achieved complete response or complete response with incomplete platelet recovery in the CPX-351 arm (47.7% vs 33.3%, respectively).

In a landmark analysis of survival from the time of transplant, median overall survival was not reached in the CPX-351 arm vs 10.25 months in the 7+3 arm—representing a 53% improvement in survival favoring CPX-351 (P = .0046). In the first 100 days after allogeneic hematopoietic cell transplantation, there were fewer deaths in the CPX-351 arm (5 vs 8). “Even though bone marrow transplant can induce significant mortality, early death rates were lower on the CPX-351 arm,” Dr. Lancet commented. ■

Disclosure: The study was sponsored by Celator. Dr. Lancet has received research funding from Pfizer and Celgene; he also has consulted for Novartis, Karyopharm, Celgene, Jazz Pharmaceuticals, Boehringer Ingelheim, Baxalta, and Janssen.


1. Lancet JE, Hoering A, Uy GL, et al: Survival following allogeneic hematopoietic cell transplantation in older high-risk acute myeloid leukemia patients initially treated with CPX-351 liposome injection versus standard cytarabine and daunorubicin: Subgroup analysis of a large phase III trial. 2016 ASH Annual Meeting. Abstract 906. Presented December 5, 2016.

2. Lancet JE, Uy GL, Cortes JE, et al: Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) ALL. 2016 ASCO Annual Meeting. Abstract 7000.

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Expert Point of View: Armand Keating, MD

One of the issues in high-risk AML in older patients is that remissions can be achieved, but they are not durable. The concept is reasonable that CPX-351 may provide not only a bridge to transplant, but increase the likelihood of transplant success.
— Armand Keating, MD