Matthew S. Davids, MD, MMSc
Duvelisib (Copiktra) monotherapy achieved robust and durable responses in patients with relapsed/refractory chronic lymphocytic leukemia (CLL), according to updated data presented at the 2018 ASH Annual Meeting.
at the 2018 ASH Annual Meeting, Matthew S. Davids, MD, MMSc, the Associate Director of the Chronic Lymphocytic Leukemia Center at Dana-Farber Cancer Institute and an assistant professor of medicine at Harvard Medical School, discussed the clinical implications of this trial in patients with CLL.
OncLive: Please provide some background to the DUO trial.
: The DUO trial looked at the use of duvelisib in patients with CLL. Duvelisib is a delta-gama PI3K inhibitor that is being compared in this study to ofatumumab, a CD20-targeted monoclonal antibody. In the initial results, there was a clear advantage to duvelisib over ofatumumab. These data led to the FDA approval of the drug in September 2018.
What were the results presented at the 2018 ASH Annual Meeting?
The design of the DUO trial included a crossover portion, so patients treated with ofatumumab who experienced disease progression could then move on to duvelisib. At this meeting, I presented the updated data of the 90 patients who crossed over to duvelisib monotherapy. The patients who received duvelisib tended to do well in general. We saw responses in about three-quarters of the patients. The PFS rates were comparable to what we saw in the earlier parts of the study. There did not appear to be any detriment to being treated with ofatumumab first in terms of duvelisib response. The drug was generally well tolerated for most patients, although there are some AEs that need to be monitored closely, such as diarrhea and colitis.
One of the biggest questions we had was whether patients with different molecular markers would respond differently. We were particularly curious about the patients with the high-risk del(17p) abnormality. Fortunately, both PFS and response rates were very similar compared to the larger group.
What are the key takeaways from the trial?
Duvelisib appears to be an effective treatment option for relapsed CLL after 2 or more lines of therapy. Patients may receive a drug like ofatumumab first and still do very well on duvelisib once they progress. Although we have many different options in CLL, for a disease that is incurable for most patients, it is helpful to make new treatment options like this available.
What are some unanswered questions with duvelisib?
Going forward, we know the activity of this drug as a single agent. One of the things I would be excited to see is what this drug can do in combination with other agents. We have been running a frontline setting of duvelisib with FCR, and we are testing it with venetoclax in relapsed/refractory patients.
Davids, MS, Kuss BJ, Hillmen P, et al. The efficacy and safety of duvelisib following disease progression on ofatumumab in patients with relapsed/refractory CLL or SLL: updated results from the DUO crossover extension study. In: Proceedings from the 2018 ASH Annual Meeting; December 1-4, 2018; San Diego, California. Abstract 3140.
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