ASH 2021 | Advancements within the CLL treatment landscape
Jacqueline Barrientos, MD, MS, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, discusses novel treatment options for patients with chronic lymphocytic leukemia (CLL). Ublituximab and umbralisib, a PI3K inhibitor, are a promising treatment regimen and have demonstrated considerable efficacy in the UNITY-CLL trial (NCT02612311), where umbralisib was found to be more tolerable than existing PI3K inhibitors such as duvelisib. The combination can also serve as a bridging therapy to chimeric antigen receptor (CAR) T-cell therapy, and umbralisib with rituximab has additionally been assessed in patients pre-treated with ibrutinib. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Transcript (edited for clarity)
There’s a novel combination of ublituximab with umbralisib, for example based on the data from the UNITY trial. It’s currently undergoing FDA evaluation for approval in patients with treatment-naive or relapsed/refractory CLL. It’s a novel PI3K delta inhibitor, and it seems to have more tolerability than prior PI3K inhibitors that are currently commercially available, such as idelalisib and duvelisib...
There’s a novel combination of ublituximab with umbralisib, for example based on the data from the UNITY trial. It’s currently undergoing FDA evaluation for approval in patients with treatment-naive or relapsed/refractory CLL. It’s a novel PI3K delta inhibitor, and it seems to have more tolerability than prior PI3K inhibitors that are currently commercially available, such as idelalisib and duvelisib. We are eager to see what the longer follow-up.
On how we will use, I think that most of us will probably use it as a bridge to CAR-T therapy or another form of salvage therapy, or it’s possible that in certain patients with many comorbidities, that might be an option of care for patients that are not able to tolerate BTK inhibitors or BCL-2 inhibitors. The median progression-free survival for treatment-naïve patients is 39 months. For relapsed/refractory patients, it’s in the order of 16-19 months. So very encouraging results. Less degree of toxicity in terms of diarrhea, colitis compared to other PI3K inhibitors, and seems to be very well tolerated.
There was also a presentation by Anthony Mato’s group where they used rituximab and umbralisib after you had been on ibrutinib for a long period of time to see if you could actually achieve undetectable MRD and possibly discontinue the BTK inhibitor.
So we are still learning how to use these novel compounds and novel agents in a CLL space. I think we’re also trying to understand the role of CAR-T. When do we send our patients for CAR-T therapy? And I’m very excited about all these novel compounds that are currently being explored, because I think that we still have some patients that are unable to tolerate or that are becoming refractory to both a BTK inhibitor and a BCL-2 inhibitor, and hopefully we can have more salvage treatments, at least for them, in the near future.
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