Analysis of Prognostic Factors Predictive of Complete Response (CR) to Ibrutinib in Patients with CLL/SLL

Abstract

Introduction: Chronic lymphocytic leukemia (CLL) has a heterogeneous clinical course, with many patients (pts) experiencing relapse after initial treatment. Ibrutinib is a first-in-class once-daily, oral, inhibitor of Bruton9s tyrosine kinase indicated for treatment of pts with CLL with ≥1 prior therapy and for pts with 17p deletion CLL. Extended follow-up of ibrutinib-treated pts has demonstrated an increase in complete response (CR) rate over time (Byrd, Blood 2015; Brown, Blood 2015). This ad hoc analysis examines baseline factors predictive of CR in pts with CLL/SLL treated with ibrutinib. Methods: Univariate and multivariate analyses were performed on pooled data from studies of pts treated with either single-agent ibrutinib (PCYC-1102, PCYC-1112), or in combination with ofatumumab (PCYC-1109), to assess the prognostic value of various baseline factors on a CR to ibrutinib treatment in CLL/SLL. CR criteria were met per iwCLL parameters, including bone marrow confirmation, which was not mandated at any standard timepoint in any protocol. Both treatment-naive (TN) and previously treated (R/R) pts were included. Factors with P Results: Data from 398 pts with TN or R/R CLL/SLL were analyzed. Patients had a median age of 67 years (range, 30-86 years). At baseline, 238 (60%) pts had bulky disease ≥5 cm, 227 (57%) were Rai stage III-IV, and 230 (58%) had ECOG ≥1 status. At baseline 121 (30%) pts had del11q, 127 (32%) del17p, 242 (61%) unmutated IGHV, and 230 (58%) β-2-microglobulin levels ≥3.5 mg/L. A total of 31 (8%) pts were TN, with 38 (10%) having 1, 106 (27%) having 2, and 223 (56%) having had ≥3 prior lines of therapy, with a median of 3 prior therapies for R/R pts. Univariate analysis of prognostic factors showed that bulky disease, Rai stage at baseline, number of prior therapies, and β2-microglobulin levels at baseline had a significant effect on the odds of CR. The final multivariate model selected showed a significant effect for TN over R/R, and for bulky disease ( Conclusions: Initial response to ibrutinib is achieved early, but the median time to CR is over one year. The rate of CR reported here with longer-term ibrutinib treatment is higher than in earlier reports (Byrd 2013, O9Brien 2014). Patients with treatment naive CLL and those without bulky lymphadenopathy have better odds of attaining a CR to treatment with ibrutinib. Disclosures O9Brien:Pharmacyclics LLC, an AbbVie Company: Honoraria, Research Funding. Off Label Use: yes, discussion of ibrutinib in treatment naive CLL. Jaglowski:Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Seattle Genetics: Consultancy; Immunomedics: Research Funding. Byrd:Acerta Pharma BV: Research Funding. Bannerji:MedImmune: Research Funding; Regeneron: Research Funding; Gilead: Research Funding; AbbVie: Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; Merck: Patents & Royalties. Blum:Constellation Pharmaceuticals: Research Funding; Morphosys: Research Funding; Gilead: Research Funding; Millenium: Research Funding; Seattle Genetics: Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; Janssen: Research Funding; Novartis: Research Funding; Celgene: Research Funding. Fox:Janssen: Honoraria; Roche: Consultancy, Honoraria; Adienne: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Gilead: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau; NAPP: Consultancy; Takeda Oncology: Honoraria, Other: Travel, Accommodations, Expenses. Hillmen:AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Celgene: Research Funding. Kipps:Gilead: Consultancy; Genentech: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding. Montillo:Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Infinity: Research Funding; AbbVie: Research Funding; Gilead: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; Roche: Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau. Sharman:Gilead: Research Funding, Speakers Bureau; Janssen: Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding. Suzuki:Pharmacyclics LLC, an AbbVie Company: Employment. James:Pharmacyclics LLC, an AbbVie Company: Employment. Chu:Pharmacyclics LLC, an AbbVie Company: Employment. Coutre:Janssen: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; AbbVie: Research Funding.