Hematology
Clinical discussions on blood disorders, coagulation, transfusion medicine, and hematologic malignancies.
Recent Discussions
What factors do you take into account for recommending venetoclax/obtinutuzumab vs BTK inhibitors vs chemotherapy in front line therapy for CLL?
For most patients, either BTK inhibitor or venetoclax/obinutuzumab would be appropriate therapies. I would only consider chemotherapy (fludarabine/cyclophosphamide/rituximab) for those <65 years old with IGHV mutated disease and no high risk genetic markers. And even in these patients, I almost alwa...
For CLL patients with high-risk cytogenetics on ibrutinib who develop a cardiac event such as an MI, would you continue ibrutinib?
It depends on the cardiac event (and the CLL status). After any serious event, if the CLL is under good control (clinical CR), I think it is very acceptable to stop the ibrutinib and wait until clinical progression occurs - which can be a while for some patients (median 2 years from the E1912 study)...
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...
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?
In the BRUIN trial, among 222 patients with PLCG2 mutation data available, 18 had mutations and 204 did not. The overall response rate (ORR) was numerically lower in those with PLCG2 mutation (56% vs 84%) (Mato et al., PMID 37407001).The ORR was numerically higher in those with BTK C481 mutation com...
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.
Would you consider IV thrombolytics in patients with acute ischemic stroke, with or without a large vessel occlusion, if they have a history of von Willebrand disease (VWD), regardless of its type?
I would still consider it unless the INR >1.7 or they are on anticoagulation for some clinical reason.
How do you manage patients with atrial fibrillation having a thromboembolic infarct despite being on adequate anticoagulation?
This scenario is always challenging. In terms of anticoagulation, the efficacy of DOACs in preventing embolic events in AF patients is around 70%, which is impressive compared to warfarin but not foolproof. In cases of a second embolic event while on anticoagulation, two reasonable approaches are of...
How would you manage symptomatic, bilateral subsegmental PE developed after long air travel?
I generally consider air travel to be a relatively weak provoking factor. Although the 2020 ASH guidelines do not address this, the ASH Guidelines from 2018 on management of VTE cite a 2.8-fold increased risk for VTE associated with air travel, which is roughly similar to the increased risk associat...