Summary
Venetoclax, a first-in-class drug that selectively binds and inhibits B-cell lymphoma-2 (BCL-2) protein, has garnered a lot of attention in the treatment of people with acute myeloid leukemia (AML). The targeted therapy has proved to be a tolerable option that significantly improves survival (when used in combination with drugs like cytarabine, decitabine, or azacytidine) for older patients with AML with comorbidities that make them ineligible to receive intensive chemotherapy regimens that are otherwise used to treat the blood cancer.
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Original Article
Minority of Older AML Patients on Venetoclax Combo Have Extended Response
Oncology Times
By Sarah DiGuilio
Venetoclax, a first-in-class drug that selectively binds and inhibits B-cell lymphoma-2 (BCL-2) protein, has garnered a lot of attention in the treatment of people with acute myeloid leukemia (AML).The targeted therapy has proved to be a tolerable option that significantly improves survival (when used in combination with drugs like cytarabine, decitabine, or azacytidine) for older patients with AML with comorbidities that make them ineligible to receive intensive chemotherapy regimens that are otherwise used to treat the blood cancer.
Now, new data published as part of the 2020 ASCO Annual Meeting offers new details about how long older patients should continue on a venetoclax combination regimen (Abstract 7531). The analysis shows that even though a majority of patients will respond to treatment within the first 2 cycles, a significant minority will do well beyond that time frame and should thus continue on the combination therapy if appropriate.
“The question here was let’s go into a little more detail on the kinetics of response,” explained Courtney D. DiNardo, MD, MSCE, Associate Professor in the Department of Leukemia in the Division of Cancer Medicine at MD Anderson. The significant finding here was that some patients will have success with the treatment regimen after the second cycle, typically between cycles 3 and 4.
For the analysis, the study team looked at data from two open-label trials of venetoclax used in combination with either azacytidine, decitabine, or low-dose cytarabine for the treatment of patients with newly diagnosed AML. The data included 197 patients in total, who were all at least 61 years old.
A total of 83 patients (42%) responded to the treatment within the first 2 cycles of treatment. Another 44 patients (22%) responded later. And 70 patients (36%) did not respond. Duration of response was longer on average for the early responders, but still significant for the later responders. Median duration of response for the early responders was 21.2 months and 8.1 months for the later responders.
The analysis also identified two factors that were associated with a higher likelihood of a patient being in the late-responder group and still responding: having achieved a morphologic leukemia free state within the first 2 cycles of treatment and having de novo AML.
The takeaway that learned from this research was, DiNardo noted, that “the majority of patients respond early. But a significant minority do well later on, too.”
DiNardo added that most patients were able to tolerate the treatment regimen relatively well. The most common side effect in both studies was febrile neutropenia (occurring in 40 percent of patients). But it was uncommon for patients to discontinue the trial because of adverse side effects.
The main limitation of the data, she said, is that the analysis pools results from two different clinical trials. For one of the clinical trials (the study that looked at venetoclax combined with cytarabine), prior treatment of myelodysplastic syndrome, including hypomethylating agents, was allowed; whereas it was not allowed in the other trial. And this analysis was not a randomized trial itself.
The data do have implications for clinical practice, DiNardo noted. They suggest that if an older adult with newly diagnosed AML is doing well on a venetoclax combination therapy, they should continue on it to increase their likelihood of a complete response, especially if they have one of these two characteristics identified in this study associated with a higher likelihood of a later response.
“If I have a patient doing well on the therapy—not a complete response, but doing well otherwise—definitely for that patient I would continue with the venetoclax combination therapy to get that complete response,” DiNardo stated.
Additional research on this drug combination is needed, however, to better inform how it could be integrated into practice, Gary Schiller, MD, Professor of Medicine and Director of the Hematological Malignancies/Stem Cell Transplantation Unit at the UCLA Jonsson Comprehensive Cancer Center (who was not involved in the study), shared with Oncology Times. “How much cytopenia was there? How much transfusion dependence was there? And what did combined treatment cost?”
There is a randomized trial of venetoclax combination therapies that is ongoing for older patients with newly diagnosed AML.
Additional detail of how to best prescribe the therapy will be significant, DiNardo said. “Venetoclax combination therapies are really important for our older adult AML patients. We are now understanding more and more how it works.”
Sarah DiGiulio is a contributing writer.