Bruton tyrosine kinase (BTK) inhibitor therapy is effective in patients with chronic lymphocytic leukemia (CLL) who are resistant to prior venetoclax treatment, according to a new study presented at the European Hematology Association (EHA) Virtual Meeting (June 11-21, 2020).
Venetoclax and BTK inhibitors have shown to be effective in treating relapsed or refractory CLL, including disease with traditional adverse prognostic factors. However, progressive disease is common in patients treated with venetoclax after long-term follow-up. Prospective studies have demonstrated the efficacy of venetoclax after ibrutinib therapy, but limited data exist to inform therapy for venetoclax-resistant CLL.
Thomas E Lew, MD, The Royal Melbourne Hospital and Peter MacCallum Cancer Center (Australia), and colleagues designed a study aimed at describing the response, progression-free survival (PFS), and overall survival (OS) of patients with receiving BTK inhibitor therapy for venetoclax-resistant CLL. Researchers also sought to better understand significant associations between pre-BTK inhibitor variables and PFS.
A total of 23 consecutive patients with relapsed or refractory CLL who received BTK inhibitor therapy for CLL progressing on venetoclax within one of four clinical trials from September 2011 to September 2019 were retrospective reviewed. Researchers noted that seven patients had received concurrent rituximab, progressive disease occurred during continuous venetoclax therapy in 22 patients, and progressive disease occurred during venetoclax retreatment in one patient with disease relapse after interrupting therapy.
Patients received either ibrutinib (420 mg/day; n = 21) or zanubrutinib (160 mg BD; n = 2). The median patient age at BTK inhibitor initiation was 72 years and the median number of prior lines of therapy was four. No patients had been previously treated with BTK inhibitors or idelalisib.
Dr Lew and colleagues found that 91% (n = 20) of evaluable patients had objective responses to BTK inhibitor therapy. The median PFS after BTK inhibitor therapy was 34 months (95% CI, 10.4 to undefined). At a median survivor follow-up range of 33 months, 48% (n = 11) of patients remained on BTK inhibitor therapy.
The median OS after BTK inhibitor therapy initiation was 42 months (95% CI, 34.2 to undefined), researchers added.
In their concluding remarks, authors of the study wrote that BTK inhibitor therapy is effective for patients with heavily pretreated, high-risk CLL after progression on venetoclax. They also noted that this trend remained significant in patients with prior Richter transformation in remission and in patients with CLL harboring a BCL2 Gly101Val mutation.—Zachary Bessette
