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ICML 2025 | Challenges associated with treating double-refractory CLL & the need for improved therapies
Ryan Jacobs, MD, Levine Cancer Institute, Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Charlotte, NC, discusses the growing need for improved treatment options for patients with double-refractory chronic lymphocytic leukemia (CLL). Dr Jacobs highlights that the non-covalent BTK inhibitor pirtobrutinib is a good option, although its efficacy can be limited in this population. This interview took place during the 18th International Conference on Malignant Lymphoma (18-ICML) in Lugano, Switzerland.
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Transcript
Yes, so now we’re jumping from first-line to at least third line for most patients, which thankfully our first- and second-line treatment options between covalent BTK and BCL2 inhibition with venetoclax-based treatments are so good. The number of patients needing third-line treatment, I feel like has overall, third line plus has overall gone down, but there are some and a growing number that as they progress through these treatments are going to need options...
Yes, so now we’re jumping from first-line to at least third line for most patients, which thankfully our first- and second-line treatment options between covalent BTK and BCL2 inhibition with venetoclax-based treatments are so good. The number of patients needing third-line treatment, I feel like has overall, third line plus has overall gone down, but there are some and a growing number that as they progress through these treatments are going to need options. The clear best option at this point that we have is the non-covalent inhibitor pirtobrutinib, but we know from updated presentations of the BRUIN trial, as well as the more recently presented BRUIN-321 study looking at use in the second line setting, that when you use pirtobrutinib following a covalent BTK inhibitor and especially if a patient has seen both a covalent BTK inhibitor and BCL2 based treatment with venetoclax, the responses are likely not going to be for very long, maybe only about a median of a year for the double exposed patients. So we already need to be thinking about what we’re going to do next. Commercially, we have CAR-T that we can evaluate for while they’re hopefully responding to pirtobrutinib, but obviously this is a place where clinical trial enrollment would be key if that’s possible.
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