On 14 thMay 2017, during iwCLL, the fifth session took place titled “Additional Considerations for the Initial Treatment of CLL.” This session was chaired by Richard Furman( Weill Cornell) and Jae Park( Memorial Sloan Kettering Cancer Center).
Thomas J. Kipps, MD, PhD, from the University of California, San Diego, Moores Cancer Center, California, USA, gave a presentation during this session titled “Outcomes of Ibrutinib-Treated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia With High-Risk Prognostic Factors in an Integrated Analysis of 3 Randomized Phase 3 Studies.”
Del(17p), del(11q), and unmutated IGHV are prognostic factors for poor outcomes after chemo-immunotherapy for CLL/SLL patients. In the phase II PCYC-1102/1103 study (newly diagnosed = 31; R/R = 101), multivariate analysis identified del(17p) as an independent prognostic impact for worse PFS or OS.
Data from the RESONATE, RESONATE-2, and HELIOStrials were pooled and analyzed based on IGHV mutational status, del(11q), trisomy 12, and complex karyotype. Impact of del(17p) was not assessed for efficacy analyses as patients with this genetic abnormality were excluded from two of the three trials. PFS for comparator patients was also included to provide context. Multivariate analysis was undertaken to determine the risk/prognostic factors associated with PFS.
It was found that, after a median follow-up of 36.4 months (95% CI, 35.8–37.1), PFS at 36 months in ibrutinib-treated patients was 70% for unmutated IGHV compared to 77% for mutated IGHV.
Thomas J. Kipps concluded the talk by stating that ibrutinib-treated patients with trisomy 12 had significantly higher CR rate; however, PFS and OS were similar compared to those without trisomy 12. Unmutated IGHV, del(11q), and complex karyotype were adverse prognostic factors for PFS in comparator-treated patients, but not in those treated with ibrutinib. This integrated analysis found that patients with del(11q) had longer PFS than patients without del(11q). Lastly, results suggest that genomic risk factors associated with poor outcomes with traditional therapies have less relevance with ibrutinib treatment.