11q Deletion (del11q) Is Not a Prognostic Factor for Adverse Outcomes for Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Treated with Ibrutinib: Pooled Data from 3 Randomized Phase 3 Studies

• Published in: Blood 2016-12, Vol.128 (22), p.2042-2042
• Main Authors: Kipps, Thomas J., Hillmen, Peter, Demirkan, Fatih, Grosicki, Sebastian, Coutre, Steven E., Barrientos, Jacqueline C., Barr, Paul M., Janssens, Ann, Byrd, John C., O'Brien, Susan M., Fraser, Graeme, Jaeger, Ulrich, Cramer, Paula, Stilgenbauer, Stephan, Chanan-Khan, Asher A., Salman, Mariya, Solman, Isabelle, Cheng, Mei, Phelps, Charles, Ninomoto, Joi, Howes, Angela, James, Danelle F., Hallek, Michael
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V128.22.2042.2042

Background: Patients (pts) with CLL/SLL that have del11q tend to have relatively short remission durations and shorter overall survival (OS) with standard chemotherapy regimens. Ibrutinib (ibr), a first-in-class, oral, once-daily inhibitor of Bruton’s tyrosine kinase (BTK) is indicated by the US FDA for the treatment of pts with CLL/SLL and allows for treatment without chemotherapy. In phase 3 studies, treatment with single-agent ibr was superior to treatment with ofatumumab (ofa) in relapsed/refractory (R/R) CLL/SLL (RESONATE; Byrd, N Engl J Med 2013) or chlorambucil (clb) in treatment-naïve (TN) CLL/SLL (RESONATE-2; Burger, N Engl J Med 2015); treatment with ibr + bendamustine/rituximab (BR) was also superior to treatment with BR in R/R CLL/SLL (HELIOS; Chanan-Khan, Lancet Oncol 2016). We examined the outcome of pts in these 3 studies who did or did not have del11q to determine the impact of del11q on clinical outcomes. Methods: In RESONATE, pts with R/R CLL/SLL received ibr 420 mg/day until progressive disease (PD) or unacceptable toxicity (tox) vs ofa for up to 24 weeks (300 mg week 1, 2000 mg weekly for 7 weeks, 2000 mg every 4 weeks for 16 weeks). In RESONATE-2, pts ≥65 years of age with TN CLL/SLL (excluding del17p) received ibr 420 mg/day until PD or tox vs clb 0.5 mg/kg (up to max of 0.8 mg/kg) on days 1 and 15 of each 28-day cycle (≤12 cycles). In HELIOS, pts with R/R CLL/SLL (excluding del17p) received BR (≤6 cycles) with or without ibr 420 mg/day (starting on day 2 of cycle 1) followed by single-agent ibr or placebo continued until PD or tox. Data from pts in the 3 studies were pooled (ibr pool, comparator pool) and analyzed based on whether or not their CLL/SLL had del11q. We performed a multivariate analysis to examine for risk factors prognostic for survival (del11q del17p, age, sex, race, current Rai stage, baseline ECOG PS, number of prior therapies, cytopenias; no multiplicity adjustment). Results: A total of 1210 pts with del11q data were included in the analysis: 609 in the ibr pool (179 with del11q, 430 without del11q) vs 601 in the comparator pool (149 with del11q, 452 without del11q). Demographics and baseline characteristics were generally similar in pts regardless of del11q status; differences of more than 10% included proportions with bulky disease ≥5 cm (63% vs 49%) and unmutated IGHV (88% vs 72%) in pts with or without del11q, respectively. Median lymphadenopathy and absolute lymphocyte counts were also higher in pts with del11q