There are many new agents being investigated for the treatment of chronic lymphocytic leukemia (CLL) that will hopefully improve outcomes for patients with the disease, explained Dr. Adam Kittai.
At the CURE® Educated Patient® CLL Summit, Kittai, an assistant professor at The James Cancer Center at The Ohio University Cancer Center, discussed promising agents for CLL that are currently being analyzed in clinical trials.
“Although there have been great improvements, specifically for CLL, we still have not cured CLL. And questions remain. We want to be able to best determine how if what we’re doing is what we should be doing. And that’s the only way to do that through a clinical trial,” Kittai said in his presentation.
Jaypirca May Be a Less Toxic BTK Inhibitor
The first drug that Kittai mentioned is Jaypirca (pirtobrutinib), a non-covalent BTK inhibitor that is currently being investigated in the BRUIN trial for patients who progressed on a covalent BTK inhibitor, such as Imbruvica (ibrutinib), Calquence (acalabrutinib) or Brukinsa (zanubrutinib).
“Covalent BTK inhibitors bind to the BTK protein (on cancer cells) in a very specific way,” Kittai explained. “(Jaypirca) is the next version of BTK inhibitor … it binds differently. This drug was designed to work specifically for patients who’ve already received those first-generation BTK inhibitors.”
Kittai said that Jaypirca is more selective in the way that it binds to the BTK molecule. In doing so, it is less likely to interact with other nearby molecules — an issue that can sometimes happen with the currently approved BTK inhibitors — thereby causing side effects.
“So the suspicion is that (Jaypirca) will be less toxic than other BTK inhibitors,” he said.
Jaypirca is currently FDA-approved for the treatment of mantle cell lymphoma, and “it will probably be approved for CLL some time soon,” according to Kittai.
CAR-T Cell Therapy for CLL
CAR-T cell therapy, which stands for “chimeric antigen receptor” T-cell therapy works by taking out patients’ cells, engineering their immune T cells to find and fight cancer, expanding the number of these cells and then infusing them back into the patient.
“This has been big news in the diffuse large B-cell lymphoma (DLBCL) world, and now it looks like it’s coming to CLL,” Kittai said, referring to the current CAR-T cell therapy, Breyanzi (lisocabtagene maraleucel), that is currently approved for DLBCL.
Breyanzi is currently being analyzed in the CLL space in the Transcend-004 clinical trial, which includes adults with CLL who received two or more lines of prior therapy, including a prior BTK inhibitor.
Study findings showed that the median overall survival (time from treatment until death of any cause) was 43.2 months and patients who responded to the therapy tended to do much better than non-responders. CLL-related side effects, such as neurotoxicity and cytokine-release syndrome, should also be considered before a patient and their care team decide on treatment with a CAR-T cell therapy.
“These are pretty severe toxicities that we really have to watch and monitor. And it’s the reason why car T cell therapy hasn’t really been moved to the frontline or second line for CLL. Because we have these other two drugs that are just remarkably safe and work really well,” Kittai said. “So I think this drug really should be reserved for patients who have not gotten who’ve received our standard of care, but toxicities are something that we do need to work on and make better over time.”
Now, a phase 3 trial is currently planned to continue the investigation of this CAR-T cell therapy in patients with CLL.
“These are good results for patients with no standard of care. And we’re expecting to see an FDA approval for this drug in the near future,” Kittai said.
Kittai concluded his presentation emphasizing the importance of participation in clinical trials.
“Get involved in clinical trials,” he said. “(Jaypirca) and Breyanzi look like great drugs for patients who’ve already received standard of care, and there are a lot of drugs to be hopeful about.”
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