Researchers have been evaluating whether achievement of minimal residual disease (MRD) can potentially serve as a marker for treatment interruption or stoppage in hematologic malignancies, including chronic lymphocytic leukemia (CLL). To date, few studies have evaluated the rate of MRD negativity among targeted agents in CLL. In the IcICLLe study, 20 treatment-naïve patients and 20 relapsed/refractory patients with CLL received ibrutinib until complete remission with <0.01% MRD in the peripheral blood and bone marrow or disease progression. Subsequently, the IcICLLe Extension Study continued IcICLLe to examine the efficacy and safety of ibrutinib plus obinutuzumab in 40 patients, 10 of whom had received prior ibrutinib on the IcICLLe trial. Initial results showed promise, and at the ASH 2018 Annual Meeting, researchers reported on the 18-month follow-up data.
Patients participating in the extension study received continuous ibrutinib with 6 cycles of obinutuzumab given over 6 months. MRD assessment was performed according to European Research Initiative on CLL guidelines with a maximum detection limit of 0.001%/10–5. In the 34 patients reaching Month 9 Disease Response Assessment, 5 of 10 (50%) of patients receiving prior ibrutinib treatment achieved MRD response at 3 months after completion of obinutuzumab treatment, compared with 2 of 30 (7%) ibrutinib-naïve patients at the same time point.
The addition of obinutuzumab was also associated with a greater depth of MRD depletion than observed in patients treated with ibrutinib monotherapy, particularly in patients who had received ibrutinib for at least 1 year before initiation of the extension study. Furthermore, peripheral blood MRD levels continued to improve in both groups of patients 6 months after obinutuzumab was discontinued.
Study results suggest that the addition of obinutuzumab to ibrutinib may result in a substantial improvement in the depletion of CLL cells, particularly when obinutuzumab was introduced after more than 1 year of ibrutinib treatment. The addition of obinutuzumab may be effective at improving MRD response rates, especially in patients whose tumor burden was already low after prior ibrutinib therapy.
Rawstron A, et al. ASH 2018. Abstract 181.