Thanks for your input, [~Connie--Batlevi--leec@ ] ! Would anybody else consider using this combination? What results or further support would you like to see from Phase 3 trials?

BOVEN (obin, ven, zanubrutinib) is an excellent demonstration of BCL2, BTK and CD20 therapy. After median surveillance after treatment of 15·8 months, 94% of patients had undetectable MRD.

Key Points
• Source: Biomarker Research
• Conclusions: “In this review, by focusing on CLL and MCL, we discussed the rationale for the combinational use and summarized the current data on the combinations of BTK inhibitors and venetoclax in patients with CLL and MCL.”
• In various clinical trials, ibrutinib has demonstrated excellent effects with manageable toxicities. Acalabrutinib and zanubrutinib, which are second-generation BTK inhibitors, have also exhibited great clinical outcomes. BTK inhibitor monotherapy, however, necessitates continuous application, with resistance and adverse effects invariably cropping up.
• The first-in-class BTK inhibitor ibrutinib has shown remarkable therapeutic effects and manageable toxicities in multiple clinical trials. The second-generation BTK inhibitors, including acalabrutinib and zanubrutinib, also have shown remarkable efficacies. However, using BTK inhibitors as monotherapies requires continuous treatment, with resistance and adverse events inevitable.
• “The addition of the BCL2 inhibitor venetoclax to BTK inhibitor may improve the therapeutic effects and result in deeper responses, providing a potential fixed-duration treatment, especially for patients with CLL,” wrote the authors.
• Double combination is similarly safe vs ibrutinib or venetoclax monotherapy. Of note, atrial fibrillation occurs in 5%-15% of patients, which is comparable to monotherapy.
• Triplet combination with ibrutinib, obinutuzumab, and venetoclax was highly active and could result in durable responses in MCL cases, per previous data.
• The authors wrote, “The combination of BTK and BCL2 inhibitors is highly active, especially in patients with CLL. Although continuous BTK inhibitor use has been demonstrated to be superior to chemoimmunotherapy in TN patients with CLL, it remains to be determined if a fixed-duration treatment with ibrutinib plus venetoclax has a significant advantage over chemoimmunotherapy.”
• It remains to be elucidated whether combining BTK and BCL2 inhibitors outperforms BTK inhibitor monotherapy or BCL2 inhibitor plus a CD20-antibody in CLL.