CPX-351 Plus Venetoclax Tolerable in Patients with Acute Myeloid Leukemia

Tapan Kadia, MD

CPX-351 used in combination with venetoclax was tolerable in patients with Acute Myeloid Leukemia (AML), according to a study presented at the American Society of Hematology (ASH) 2020 virtual conference.

Furthermore, the investigators reported that virtually all responders were cleared to move on to stem cell transplant.

A team led by Tapan M. Kadia, MD, Department of Leukemia, MD Anderson Cancer Center, Houston, Texas, evaluated the safety and efficacy of the combination therapy in patients with Relapsed/Refractory AML.

Previous research has shown CPX-351, a liposomal formulation of cytarabine, to lead to higher response rates, better tolerability, and survival in patients with secondary AML when compared with 7+3. Further, addition of venetoclax to hypomethylating agents has also been shown to lead to greater improvement in response rate and survival than homethylating agents alone.

Kadia and team enrolled 18 patients with a median age of 51 years. Overall, 94% of patients had Relapsed/Refractory AML, and the median number of prior therapy was 2.

More than half (67%) were assigned to the lead-in safety cohort, which received 300 mg as the starting effective dose of venetoclax. Dosage was administered between days 2 – 21, and interruption of venetoclax was permitted after day 14 if bone marrow hypocellular and had no evidence of leukemia.

After safety was established, the investigators developed two more cohorts. Cohort A (28%) included patients with Relapsed/Refractory AML, and Cohort B included only 1 patient with newly diagnosed AML.

For both cohorts, dosage of CPX-351 was constant on days 1, 3 and 5 of induction and days 1 and 3 of consolidation.

Reported Responses of Combination CPX-351 and Venetoclax

Of the 16 evaluated patients with Relapsed/Refactroy AML, 1 experienced a complete remission, 5 reached complete remission with incomplete hematologic recovery, and 1 reached a morphologic leukemia-free state. Thus, the overall response rate was 44%.

The investigators also noted that the overall response rate for patients without any prior exposure to venetoclax was 60% (6/10)—versus 17% (1/6) among those with prior exposure.

Additionally 86% of responding patients (6/7) went on to receive stem cell transplant.

The median length of overall survival was 6.4 months, and the 6-month survival rate was 53%.

Among those who responded to the combination treatment, the median 6-month survival and relapse-free survival rate were both 86%.

The 4- and 8-week mortality rates were 11% and 22% respectively.

“The starting dose level -1 was above the maximum tolerated dose of the combination; dose-limiting toxicities were prolonged neutropenia and thrombocytopenia,” they wrote.

The most frequent serious adverse events rated grades 3 and 4 were infection, nausea, pneumonia, and myelosuppression.

“CPX-351 plus 7 days of venetoclax is tolerable, with acceptable toxicities in patients with R/R AML. Within this high risk AML cohort, CPX + venetoclax demonstrated encouraging activity, particularly in those who had not received prior venetoclax,” Kadia and colleagues concluded.

They indicated that their study will continue to enroll relapsed and frontline cohorts.

The study, “Phase II Study of CPX-351 Plus Venetoclax in Patients with Acute Myeloid Leukemia (AML),” was presented at ASH 2020.