Ibrutinib trials that enrolled patients with del17p chronic lymphocytic leukemia (CLL) include a phase 2 study in treatment-naïve or relapsed/refractory (r/r) CLL (PCYC-1102) with extension (PCYC-1103), phase 3 RESONATE study of patients with r/r CLL (PCYC-1112), and phase 2 RESONATE-17 study in patients with r/r CLL (PCYC-1117).
This extension trial evaluated efficacy and safety outcomes in an integrated analysis of patients with del17p CLL and small lymphocytic lymphoma across these 3 ibrutinib trials. These data include outcomes for patients with complex karyotype (CK) CLL.1
Patients received once-daily oral ibrutinib 420 mg (n = 232) or 840 mg (n = 11) until progressive disease (PD) or unacceptable toxicity. Sustained hematologic improvement over baseline was defined as ≥56 days without transfusion support and included platelet or absolute neutrophil count increase ≥50% and/or an increase in hemoglobin of ≥2 g/dL. In PCYC-1102, CK was defined as ≥3 unrelated chromosomal abnormalities by stimulated cytogenetics.
A total of 243 CLL patients with del17p (241 r/r and 2 treatment-naive) were evaluated, with a median age of 65 years (37% ≥70 years). At baseline, 63% had Rai stage III or IV disease, and 53% had bulky disease. Median number of prior therapies was 2 (range, 1-12). The median time on study was 28 months with 66% receiving ibrutinib for more than 2 years.
Overall response rate (including partial response with lymphocytosis) was 84%. For patients with PD, Richter’s transformation tended to occur earlier with a median of 253 days (range, 31-786 days) versus CLL progression with a median of 594 days (range, 26-1572 days).
Estimated 30-month progression-free survival (PFS) was 55% (95% confidence interval [CI], 48%-62%). Estimated 30-month landmark overall survival (OS) was 67% (95% CI, 59%-74%).
Among 243 patients with del17p, adverse events occurring over the 2+-year median treatment period included neutropenia (grade 4 [highest grade], 14%), pneumonia (grade 5, 2%), hypertension (grade 3, 11%), thrombocytopenia (grade 4, 5%), and anemia (grade 4, 1%). Grade 3/4 atrial fibrillation occurred in 1% of patients. Grade 3/4 hemorrhage occurred in 1%. Almost half (45%) of patients remain on study treatment.
Researchers concluded that, in this analysis, estimated 30-month PFS and OS for ibrutinib surpass those of other therapies for del17p CLL. Patients receiving fewer prior therapies, normal lactate dehydrogenase, and those without CK experienced the most favorable PFS and OS outcomes. These data confirm ibrutinib’s robust clinical activity and survival outcomes in difficult-to-treat CLL populations.