Medical Oncology
Physician insights on cancer treatment protocols, immunotherapy, targeted therapies, and clinical trial updates.
Recent Discussions
Are there scenarios where you would consider use of capivasertib for non-AKT pathway altered patients given the efficacy seen in the overall treatment population of the CAPItello-291 trial?
While PFS curves are similar in AKT-altered and the overall population, PFS curves are much closer (HR 0.79, 0.61-1.02) in patients with AKT pathway non-altered tumors excluding unknown NGS results (Fig S2), suggesting that the majority of the efficacy is from the AKT-altered population (CAPItello-2...
How would you approach treatment for a R/R mantle cell lymphoma patient with a history of autoimmune hepatitis who has progressed on both a covalent and non-covalent BTKi?
Without the whole story, hard to know if this patient is a candidate for CAR T therapy. Presuming the answer is no, I would give venetoclax. Admittedly this is off label, but venetoclax can be very effective in this disease, both in my personal experience and in the limited available data (Davids et...
How would you treat a BTKi naive p53 mutated MCL in 1st relapse with disease noted both systemically and in the CNS?
This is a case where I would likely still use ibrutinib. We know from years of experience that it gets into the CNS, and it's an incredibly effective drug in MCL. Zanu and acala should get into the CNS, but the companies have limited PK data for CNS penetration. The harder question (I think) is whet...
Following the BRUIN data in mantle cell lymphoma, will you routinely treat with pirtobrutinib following a covalent BTKi?
Yes, this drug has demonstrated clear efficacy in a difficult-to-treat population and perhaps to date, the best safety data with a BTK inhibitor we have seen (low rates of cardiac, bleeding, and GI adverse events). There is a head-to-head study of pirtobrutinib versus covalent BTK inhibitors ongoing...
What is your approach to re-challenging BTK inhibitors for a patient who has had intolerance to several different agents?
This is a great question, and the answer is that I probably would not rechallenge with a BTK inhibitor. Many patients who develop an intolerance to a BTKi can remain on the drug with supportive care for the toxicity and/or dose reduction, which is not always effective. If someone truly had an intole...
What are your top takeaways from ASH 2023?
Gene therapy for sickle cell disease and beta thalassemia. This was the first approval of CRISPR/Cas-based therapy in humans. Ex-vivo engineering of isologous hematopoietic stem cells followed by their reinfusion after myeloablative conditioning led to induction of 40-50% fetal hemoglobin in patient...
How would you approach treatment for a R/R mantle cell lymphoma patient with a history of autoimmune hepatitis who has progressed on both a covalent and non-covalent BTKi?
Without the whole story, hard to know if this patient is a candidate for CAR T therapy. Presuming the answer is no, I would give venetoclax. Admittedly this is off label, but venetoclax can be very effective in this disease, both in my personal experience and in the limited available data (Davids et...
How would you treat a BTKi naive p53 mutated MCL in 1st relapse with disease noted both systemically and in the CNS?
This is a case where I would likely still use ibrutinib. We know from years of experience that it gets into the CNS, and it's an incredibly effective drug in MCL. Zanu and acala should get into the CNS, but the companies have limited PK data for CNS penetration. The harder question (I think) is whet...
Following the BRUIN data in mantle cell lymphoma, will you routinely treat with pirtobrutinib following a covalent BTKi?
Yes, this drug has demonstrated clear efficacy in a difficult-to-treat population and perhaps to date, the best safety data with a BTK inhibitor we have seen (low rates of cardiac, bleeding, and GI adverse events). There is a head-to-head study of pirtobrutinib versus covalent BTK inhibitors ongoing...
What is your approach to re-challenging BTK inhibitors for a patient who has had intolerance to several different agents?
This is a great question, and the answer is that I probably would not rechallenge with a BTK inhibitor. Many patients who develop an intolerance to a BTKi can remain on the drug with supportive care for the toxicity and/or dose reduction, which is not always effective. If someone truly had an intole...