BTK inhibitor therapy is an effective therapy option for patients with CLL resistant to venetoclax, according to data presented at the virtual 2020 EHA Annual Congress.

Bruton tyrosine kinase inhibitor (BTKi) therapy is an effective option for patients with chronic lymphocytic leukemia (CLL) resistant to venetoclax, according to study findings that were presented at the virtual 2020 European Hematology Association Annual Congress (Blood. 2020;135[25]:2266-2270). 

“[I]brutinib achieves durable disease control in treatment-naive and [relapsed/refractory] CLL, including in high-risk subgroups. Acalabrutinib and zanubrutinib are next-generation BTKis with greater selectivity for BTK and similarly high response rates,”explained Victor S. Lin, MD, The Royal Melbourne Hospital and Peter MacCallum Cancer Center, Australia, and co-researchers.

“Although prospective studies have demonstrated the efficacy of venetoclax postibrutinib, limited data exist to inform choice of therapy post-venetoclax,” continued Dr Lin et al, who herein describe the characteristics and outcomes of patients with relapsed or refractory CLL given BTKi therapy for progressive disease after discontinuation of venetoclax.

A total of 23 patients (median age, 72 years) with relapsed or refractory CLL who received BTKi therapy for disease that progressed with venetoclax between September 2011 and September 2019 were retrospectively reviewed for this study.

Venetoclax doses ranged from 100 mg to 600 mg daily, and CLL that progressed after was treated with ibrutinib 420 mg daily or zanubrutinib 160 mg twice daily.

Patients in the study had received a median of 4 prior lines of therapy. Notably, no patients had been previously treated with BTK inhibitors or idelalisib.

According to Dr Lin and colleagues, 7 patients received concurrent rituximab; 22 had progressive disease with continuous venetoclax therapy; and 1 patient had progressive disease during venetoclax retreatment with disease relapse after therapy interruption.

Approximately 90% of patients had objective responses to BTKi therapy. The median rate of progression-free survival after BTK inhibitor therapy was 34 months.

As of a median survivor follow-up time frame of 33 months, 48% of patients were still receiving BTKi therapy.

“These data indicate that BTKi therapy is an effective therapeutic option for patients with heavily pretreated, high-risk CLL after progression on venetoclax, including patients with prior RT in remission or CLL harboring the BCL2 Gly101Val mutation,” Dr Lin and colleagues wrote.

“We await further prospective trial data to validate therapeutic sequencing in the novel agent era,” they concluded.—Alexis Hyams