Dr Ghia on the Rationale for Evaluating Pirtobrutinib in Relapsed/Refractory CLL

“BRUIN CLL-321 is a randomized phase 3 study where pirtobrutinib, a non-covalent BTK inhibitor, was compared with physician’s choice [treatment] between bendamustine [plus] rituximab or idelalisib [plus] rituximab in the relapsed/refractory setting of patients with chronic lymphocytic leukemia.”

Paolo Ghia, MD, a full professor of medical oncology at the Università Vita Salute San Raffaele, highlighted the rationale for evaluating pirtobrutinib (Jaypirca) for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who had previously received a covalent BTK inhibitor.

The randomized phase 3 BRUIN CLL-321 study (NCT04666038) included adult patients with CLL who received a prior covalent BTK inhibitor. There was no limit on the number of prior lines of therapy and those with prior history of atrial fibrillation were allowed.

Patients with relapsed/refractory CLL were randomly assigned to receive either pirtobrutinib or bendamustine plus rituximab (BR) or idelalisib (Zydelig) plus rituximab, Ghia began. The difference between BRUIN CLL-321 and other clinical trials is that all patients on the study had previously been treated with a covalent BTK inhibitor, he emphasized. Findings from BRUIN CLL-321 revealed that pirtobrutinib demonstrated efficacy benefits compared with physician’s choice therapy, he explained.

Specifically, at the final overall survival analysis, the median independent review committee–assessed progression-free survival (PFS) was 14 months (95% CI, 11.2-16.6) in the pirtobrutinib group compared with 8.7 months (95% CI, 8.1-10.4) in the idelalisib/rituximab and BR groups (HR, 0.54; 95% CI, 0.39-0.75; P = .0002). Additionally, the median investigator-assessed PFS was 15.3 months (95% CI, 12.8-19.9) vs 9.2 months (95% CI, 7.3-10.6) in the pirtobrutinib and physician’s choice groups, respectively (HR, 0.48; 95% CI, 0.34-0.67).

With a median time-to-next-treatment (TTNT) of 24 months (95% CI, 17.8-29.7) in the pirtobrutinib group, this could potentially provide a new treatment option for the treatment of patients with relapsed/refractory CLL, Ghia concluded. Of note, the median TTNT in the pirtobrutinib group compared with 10.9 months (95% CI, 8.7-12.5) in the physician’s choice group (HR, 0.37; 95% CI, 0.25-0.52).