medwireNews: Combining ibrutinib rather than chlorambucil with obinutuzumab significantly improves progression-free survival (PFS) in previously untreated patients with chronic lymphocytic leukemia (CLL), phase III study data show.
The improvement was observed among nearly all subgroups of patients, including those with high-risk features and patients with small lymphocytic lymphoma, and therefore provides “an alternative first-line treatment option,” in this setting, write Carol Moreno (University of Barcelona, Spain) and colleagues in The Lancet Oncology.
The results of the iLLUMINATE study, which were also presented at the 60th American Society of Hematology Annual Meeting in San Diego, California, USA, showed that the 113 patients who were randomly assigned to receive ibrutinib (420 mg/day) plus intravenous obinutuzumab (100 mg on day 1, 900 mg on day 2, 1000 mg on days 8 and 15 of cycle 1 and day 1 of cycles 2–6) had a significant 77% lower risk for disease progression or death than the 116 who received oral chlorambucil (0.5 mg/kg on days 1 and 15 of each 28-day cycle for six cycles) alongside the same obinutuzumab regimen.
The patients had either previously untreated chronic lymphocytic leukemia (93%) or small lymphocytic lymphoma (7%) and were either aged 65 years and older or younger than 65 years but with coexisting conditions.
At the end of the median 31.3-month follow-up period, 79% of patients in the ibrutinib plus obinutuzumab group were alive and disease-free versus 36% of those in the chlorambucil plus obinutuzumab group, with median PFS not reached in the former group and 19.0 months in the latter.
Similar findings were observed in the subgroup of 148 high-risk patients with del17p, del11q, TP53 mutations, or wild-type IGHV. In this group, the estimated 30-month PFS rate was 77% for ibrutinib plus obinutuzumab versus 16% in the chlorambucil plus obinutuzumab group, with patients in the ibrutinib group having a significant 85% reduced risk for disease progression or death.
Ibrutinib-treated patients were also more likely than those given chlorambucil to achieve an overall response (88 vs 73%) as well as a complete response (19 vs 8%), and were less likely to receive subsequent treatment (4 vs 44%).
Median overall survival was not reached in either group and the researchers note that adverse events were “consistent with the known safety profiles of the individual drugs, with no new safety signals identified.”
Serious adverse events occurred in 58% of patients in the ibrutinib group and 35% of those in the chlorambucil group, with one treatment-related death occurring in each arm.
Moreno et al conclude: [T]he results from iLLUMINATE show that ibrutinib plus obinutuzumab is an effective chemotherapy-free treatment option for previously untreated patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma, including in patients with high-risk disease.”
By Laura Cowen
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