Medical Oncology
Physician insights on cancer treatment protocols, immunotherapy, targeted therapies, and clinical trial updates.
Recent Discussions
Would you ever consider using ibrutinib in CLL patients who have received first line acalabrutinib and then progressed?
There is no benefit of switching between covalent BTKi (Acalabrutinib, zanubrutinib, or ibrutinib) especially in CLL which, in most cases, is driven by a C481S which renders all three ineffective. The only rationale situation to switch between the three would be intolerance. In this situation, switc...
Would you ever consider using ibrutinib in CLL patients who have received first line acalabrutinib and then progressed?
There is no benefit of switching between covalent BTKi (Acalabrutinib, zanubrutinib, or ibrutinib) especially in CLL which, in most cases, is driven by a C481S which renders all three ineffective. The only rationale situation to switch between the three would be intolerance. In this situation, switc...
How do you approach treatment for a fit patient with unmutated CLL who has progressed after BTKi and venetoclax containing regimens in the first and second line?
Original answer: February 10, 2023 This is a tough situation and we are seeing increasing number of patients who have failed both BTKi and BCL2i. Clinical trial enrollment with non covalent BTKi, or other novel strategies including CAR T cell therapy should be considered. PI3K inhibitors are also ap...
How do you approach treatment for a fit patient with unmutated CLL who has progressed after BTKi and venetoclax containing regimens in the first and second line?
Original answer: February 10, 2023 This is a tough situation and we are seeing increasing number of patients who have failed both BTKi and BCL2i. Clinical trial enrollment with non covalent BTKi, or other novel strategies including CAR T cell therapy should be considered. PI3K inhibitors are also ap...
Do complex cytogenetics have any therapeutic or prognostic relevance in CLL?
In this patient, the finding of a TP53 mutation trumps all, including complex karyotype. In the absence of TP53 mutation or deletion of 17p13.1 (the TP53 locus) on FISH, complex karyotype of 5 or greater abnormalities is generally associated with shorter time to treatment and PFS on both chemoimmuno...
Do complex cytogenetics have any therapeutic or prognostic relevance in CLL?
In this patient, the finding of a TP53 mutation trumps all, including complex karyotype. In the absence of TP53 mutation or deletion of 17p13.1 (the TP53 locus) on FISH, complex karyotype of 5 or greater abnormalities is generally associated with shorter time to treatment and PFS on both chemoimmuno...
How do CLL patients with downstream treatment-resistant mutations such as PLCG2 respond to pirtobrutinib?
Although BTK/PLCG2 mutations are present in patients with CLL relapsing on covalent BTK inhibitors, more than one-third of them DO NOT harbor such mutations even after high-sensitivity analyses. Additional genetic mechanisms, in particular aberrant activation of the BcR and NF-κB pathways, may be re...
How do CLL patients with downstream treatment-resistant mutations such as PLCG2 respond to pirtobrutinib?
Although BTK/PLCG2 mutations are present in patients with CLL relapsing on covalent BTK inhibitors, more than one-third of them DO NOT harbor such mutations even after high-sensitivity analyses. Additional genetic mechanisms, in particular aberrant activation of the BcR and NF-κB pathways, may be re...
Does tolerance of prior BTKi therapy or specific agent used (e.g., ibrutinib, acalabrutinib) influence your starting dose of pirtobrutinib?
Not really. I generally start pirtobrutinib at the standard dose of 200 mg daily.
Does tolerance of prior BTKi therapy or specific agent used (e.g., ibrutinib, acalabrutinib) influence your starting dose of pirtobrutinib?
Not really. I generally start pirtobrutinib at the standard dose of 200 mg daily.