At a median follow-up of 31.3 months, the median PFS by independent review committee assessment was not reached for ibrutinib-obinutuzumab compared with 19.0 months for chlorambucil-obinutuzumab (P <.0001). This finding translates to a 74% reduction in risk for progression or death. PFS rates at 30 months were 79% and 31% with ibrutinib-obinutuzumab and chlorambucil-obinutuzumab, respectively. Furthermore, PFS benefit with ibrutinib-obinutuzumab was consistent across the high-risk subgroups examined, which included patients with del(17p)/TP53 mutation, del(11q), and/or unmutated IGHV. Similarly, ORRs and complete response rates were higher with ibrutinib-obinutuzumab versus chlorambucil-obinutuzumab. MRD was undetectable in blood and/or bone marrow for 35% of patients with ibrutinib-obinutuzumab versus 25% with chlorambucil-obinutuzumab. OS rates with median follow-up of 31 months were statistically similar for the 2 groups; however, it should be noted that 40% of patients randomized to chlorambucil-obinutuzumab crossed over to single-agent ibrutinib as second-line therapy.
In the ibrutinib-obinutuzumab arm, grade ≥3 adverse events included neutropenia (28%) and thrombocytopenia (18%), whereas in the chlorambucil-obinutuzumab arm, grade ≥3 neutropenia and thrombocytopenia rates were 46% and 10%, respectively. Grade ≥3 atrial fibrillation occurred in 3% of ibrutinib-obinutuzumab patients; no grade ≥3 atrial fibrillation was reported in the chlorambucil-obinutuzumab arm. Infusion-related reactions occurred more frequently in the chlorambucil-obinutuzumab arm (8% vs 2%). These adverse event rates were seen despite the fact that median duration of treatment was 29.3 months for patients treated with ibrutinib-obinutuzumab versus 5.1 months for chlorambucil-obinutuzumab.
Ibrutinib-obinutuzumab resulted in superior PFS regardless of high-risk genomic features compared with chlorambucil-obinutuzumab. Furthermore, response rates and depth of remission (complete response and undetectable MRD) were higher with ibrutinib-obinutuzumab. No new safety signals emerged. Researchers concluded that ibrutinib-obinutuzumab represents an effective chemotherapy-free treatment option for first-line CLL/SLL, including the high-risk population.
Moreno C, et al. ASH 2018. Abstract 691.