(ChemotherapyAdvisor) – Ibrutinib (PCI-32765) is highly active and well tolerated in relapsed or refractory (R/R) and elderly treatment-naïve (TN) patients with chronic myeloid leukemia (CLL), according to a team of US-based researchers. This conclusion is based on an abstract entitled “The Bruton’s Tyrosine Kinase Inhibitor Ibrutinib is Highly Active and Tolerable in Relapsed or Refractory (R/R) and Treatment-Naive (TN) CLL Patients, Updated Results of a Phase IB/II Study,” which was presented at the 17th Congress of the European Hematological Association in Amsterdam, The Netherlands.

Ibrutinib (PCI-32765), an oral, selective, irreversible inhibitor of Bruton’s Tyrosine Kinase (BTK), inhibits proliferation, migration and adhesion in CLL cells, noted lead author Susan O’Brien, MD, of University of Texas, M.D. Anderson Cancer Center, Houston, TX. In this multi-cohort Phase 1b/2 trial, investigators evaluated 2 doses of single-agent ibrutinib in TN and R/R CLL/SLL patients to determine safety, preliminary efficacy, and pharmacokinetics.

Patients enrolled into one of two R/R cohorts based on dosage (420mg or 840mg) or one of two TN cohorts who were also randomized to receive 420mg or 840mg. The 840mg TN cohort was terminated after comparable activity and safety between doses was shown in R/R patients. The majority of AEs have been graded ≤2 in severity, most commonly diarrhea, nausea, and fatigue. Response (ORR; PR+CR) in the 420mg R/R cohort was 67% with 12.6 months median follow-up. In the 840mg R/R cohort ORR is 68% at 9.3 months median follow-up. An additional 22%, and 24% of patients in these R/R cohorts, respectively, achieved a nodal response with residual lymphocytosis (NodR). With 10.7 months median follow-up the ORR in the 420mg TN cohort is 73% including 8% CRs with morphologically normal marrows. With only 4.6 months median follow-up, ORR in the 840mg TN cohort is 40%. An additional 12%, and 20% of patients in these TN cohorts, respectively, achieved a NodR. Estimated 12-month median PFS for those patients treated at 420mg dose is 88% for R/R patients and 93.3% for TN patients.

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The investigators concluded that ibrutinib (PCI-32765) is highly active and well tolerated in R/R and elderly TN CLL patients.