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SOHO 2024 | Treating CLL in the R/R setting: switching drug classes and investigational therapies
John Seymour, MBBS, FRACP, PhD, Peter MacCallum Cancer Centre, Melbourne, Australia, discusses treatment strategies for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), emphasizing that the choice of subsequent therapy depends on prior treatments used. He recommends switching between classes of drugs and highlights the potential of investigational therapies for patients refractory to multiple classes. This interview took place at the Twelfth Annual Meeting of the Society of Hematologic Oncology (SOHO 2024) congress in Houston, TX.
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Transcript
So in the setting of relapsed and refractory CLL, the strongest determinant is what agents did you use in the frontline context. So if you’ve used a BTK inhibitor, then switching class to a BCL2 inhibitor is generally preferred. If you’ve used a BCL2 inhibitor, if the disease is refractory, then switching to a BTK inhibitor. The appealing issue with time-limited treatment, particularly with BCL2 inhibitors, is the capacity to re-treat in patients with relapsing as opposed to refractory disease...
So in the setting of relapsed and refractory CLL, the strongest determinant is what agents did you use in the frontline context. So if you’ve used a BTK inhibitor, then switching class to a BCL2 inhibitor is generally preferred. If you’ve used a BCL2 inhibitor, if the disease is refractory, then switching to a BTK inhibitor. The appealing issue with time-limited treatment, particularly with BCL2 inhibitors, is the capacity to re-treat in patients with relapsing as opposed to refractory disease. So really those two questions are, is the disease refractory to or relapsing after? If it’s relapsing off drug, re-treating with that same class. If it’s refractory, then switching within class. If you have refractoriness to a covalent BTK inhibitor, then pirtobrutinib, the first-in-class non-covalent BTK inhibitor, is the next step. If the disease, if the patient has had intolerance or toxicity within the covalent class, then sequentially switching ibrutinib to acalabrutinib to zanabrutinib generally shows better tolerance in that setting. So they are the established therapies and then if you have disease which is refractory to both BTK inhibitors and venetoclax then we’re in the investigational context and both the immunologic therapies CAR-T and bispecific antibodies have the greatest promise in that dual class refractory disease group.
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