In the GELTAMO ICML-2015 study, treatment with frontline ibrutinib in combination with rituximab demonstrated high rates of efficacy in patients with indolent mantle cell lymphoma (MCL), with promising rates of measurable residual disease (MRD) negativity. The combination also had a predictable toxicity profile, according to study presented by Eva Giné, MD, from the Hospital Clínic de Barcelona in Spain, at the 2021 International Conference on Malignant Lymphoma.
The GELTAMO ICML-2015 study is a multicenter, single-arm, open-label, phase II trial that enrolled 50 patients with previously untreated MCL who met the following criteria: no symptoms attributable to MCL, Eastern Cooperative Oncology Group score of 0-1, stable disease without a need for therapy for at least three months, non-blastoid variants, Ki-67 <30%, and largest tumor diameter ≤3 cm.
Participants received ibrutinib 560 mg daily and a total of eight doses of rituximab 375 mg/m2 (4 weekly doses during the first 28-day cycle, followed by day 1 of cycles 3, 5, 7, and 9). Per study protocol, ibrutinib could be discontinued after two years of treatment if the patient experienced sustained undetectable MRD.
After a median follow-up of 33 months, four patients discontinued treatment early due to adverse events (AEs). The overall response rate was 84%, which included a complete response (CR) rate of 80%. Among the 45 patients who were evaluable for MRD, the rate of MRD negativity in peripheral blood was 86% and 64% in bone marrow. In those who experienced CR, 72% had undetectable MRD in both peripheral blood and bone marrow.
Nineteen patients discontinued treatment after 24 months because they were in response and had undetectable MRD. Four patients experienced progressive disease at 12, 38, 40, and 52 months of follow-up, respectively; two of them eventually died due to disease progression.
Overall, the estimated progression-free and overall survival rates at 42 months were 81% and 86%, respectively. Five patients withdrew from the study due to serious AEs, including skin rash, severe aplastic anemia, pancreatic adenocarcinoma, lumbar fractures, and patient decision (n=1 for all). The most common treatment-related AEs were diarrhea (38%), neutropenia (36%), fatigue (32%), upper respiratory infection (26%), nausea (22%), and arterial hypertension (20%). The authors added that 10 patients had discontinued ibrutinib due to tolerance as of last follow-up.
Given the acceptable toxicity profile, Dr. Giné and colleagues noted that this is a promising combination for patients with MCL, particularly because it demonstrated efficacy with a limited duration of two years, rather than indefinite treatment.
Study authors report no relevant conflicts of interest.
Giné E, De La Cruz F, Ubieto J, et al. Efficacy and safety of ibrutinib in combination with rituximab as frontline treatment for indolent clinical forms of mantle cell lymphoma. Results of the GELTAMO ICML-2015 study. Presented at the 16th International Conference on Malignant Lymphoma, Virtual Edition, June 18-22, 2021.