When to use a cBTKi vs Ven-O in CLL or SLL. We individualize treatment recommendations for each patient after considering relevant pretreatment factors. (A) Patient preference is a very important factor when selecting between a cBTKi and Ven-O as initial therapy. Key differences affecting patient preference include: (1) therapy until progression or intolerance vs time-limited therapy, (2) oral therapy alone vs addition of intravenous obinutuzumab, and (3) limited vs frequent visits/laboratory testing over the first 8 weeks on therapy (refer to Section 4.2). (B) For patients with concomitant warfarin or dual antiplatelet therapy, or a history of major bleeding with ongoing bleeding risk, or a history of ventricular arrhythmias with ongoing ventricular arrhythmia risk, we strongly recommend Ven-O over a cBTKi. Although concomitant use of a nonwarfarin anticoagulation or single antiplatelet therapy, or a history of AF, influences treatment selection toward Ven-O, a second-generation cBTKi (acalabrutinib or zanubrutinib) remains a reasonable option (refer to Section 4.3). (C) When considering these molecular risk factors, the most impactful for treatment selection is 17p deletion or TP53 mutation (del(17p)/TP53M), which influences treatment selection toward a second-generation cBTKi (acalabrutinib or zanubrutinib). Given the lack of direct comparison of a cBTKi and Ven-O in this population, and taking other factors including patient preference into account, Ven-O remains a reasonable option for patients with CLL/SLL with del(17p)/TP53M (refer to Section 4.4). DAPT, dual antiplatelet therapy.