Roche’s headquarters in Basel, Switzerland

Data presented this week at the American Society of Hematology’s 2018 annual meeting for a drug recently approved for the treatment of acute myeloid leukemia showed strong response rates among a subpopulation of AML patients considered among the hardest to treat.

The data, presented at the ASH conference Monday, for AbbVie and Roche’s Venclexta (venetoclax) showed a majority of AML patients achieved complete remissions when receiving it with either a hypomethylating agent or low doses of the chemotherapy drug cytarabine. Patients in the study were either at least 60 years old or ineligible for intensive induction chemotherapy due to coexisting medical conditions. The hypomethylating agents used were Celgene’s Vidaza (azacitidine) and Otsuka Pharmaceutical’s Dacogen (decitabine). The ASH meeting, in San Diego, concluded on Tuesday.

Venclexta received accelerated Food and Drug Administration approval last month for patients aged 75 and older – combined with Vidaza or low-dose cytarabine, also known as LDAC – or ineligible for intensive induction chemotherapy. The approval was based on earlier data from the same studies presented at the ASH meeting. The had initially received accelerated approval in 2016 for chronic lymphocytic leukemia in patients with a mutation known as 17p deletion and is now approved for patients with CLL and small lymphocytic lymphoma – or SLL, a closely related disease – regardless of 17p status.

The new AML data position the drug – especially combined with hypomethylating agents – as standard of care among elderly and unfit patients in the upfront setting, said Dr. Dan Pollyea, clinical director of leukemia services at the University of Colorado in Denver and an investigator in the hypomethylating agent-combination study, in a phone interview. “This is really a revolutionary therapy for patients in this population,” he said. “Historically we’ve had no effective therapies for them.”

In the 115-patient Phase Ib hypomethylating agent study, 67 percent of patients who received Venclexta with Vidaza achieved a complete remission with at least a partial blood count recovery, known as a CR/CRh rate. The CR/CRh rate was 71 percent for those who received Venclexta and Dacogen. Among the 82 patients receiving the drug with LDAC in that Phase I/II trial, the rate of complete remission with or without full recovery of normal blood counts – also known as CR/CRi – was 54 percent. The median duration of remission in the LDAC study was 8.1 months, according to Roche’s announcement. For the Vidaza and Dacogen arms, Pollyea said the durations of remission were 21 and 15 months, respectively. No unexpected adverse events were observed in any of the three combinations.

But while the efficacy numbers appear lower in the LDAC study, Pollyea said that study had allowed patients who had previously received a hypomethylating agent for myelodysplastic syndrome, or MDS, a blood cancer that is a precursor to AML. When subtracting those patients from the LDAC study, he said, efficacy was consistent with those who received Venclexta with a hypomethylating agent. At the same time, Pollyea said LDAC is not typically used in the US because it is a “logistical nightmare” to give, but he would consider Venclexta with LDAC for patients who had already received a hypomethylating agent for MDS. LDAC is also used more frequently in Europe, where Venclexta is marketed as Venclyxto.

While the CR/CRh and CR/CRi rates for the Venclexta combinations are high, the gold standard – particularly in AML – is an improvement in overall survival. Consequently, two confirmatory Phase III trials of Venclexta – one combining it with Vidaza and the other with LDAC – are ongoing, using overall survival as their primary endpoints.

Photo: Roche

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