An evaluation of frontline tailored treatment for indolent clinical forms of mantle cell lymphoma (MCL) with ibrutinib in combination with rituximab showed a high rate of complete remissions (CR) with undetectable measurable residual disease (MRD).
The trial also assessed discontinuation of ibrutinib treatment in patients with sustained undetectable MRD.
“An MRD-driven strategy allows ibrutinib discontinuation in indolent clinical forms of MCL patients who persist with prolonged MRD and also clinical responses,” the authors, led by Eva Giné, MD, of the Hospital Clinic of Barcelona, and colleagues, wrote.
The results from the fifth-year update of the GELTAMO trial in Spain were presented during the 17th International Conference on Malignant Lymphoma in Lugano, Switzerland.
The original GELTAMO study was an open-label, phase II trial conducted at 14 Spanish GELTAMO sites. It enrolled 50 patients with previously untreated, asymptomatic MCL with a median age of 65 years old between June 2016 and December 2019. Patients received ibrutinib 560 mg daily and a total of eight doses of rituximab 375 mg/m2 (four weekly doses during the first 28-day cycle, followed by day one of cycles three, five, seven, and nine). Ibrutinib could be discontinued after two years of treatment in case of sustained undetectable MRD.
The overall response (OR) and CR rates at 12 months of treatment were 84% and 80%, respectively (including four early discontinuations). Undetectable MRD was reached in 40 (87%) of 46 evaluable cases. After 24 months, 42 of 44 patients were in response, with OR and CR rates of 86% and 84%, respectively. Undetectable MRD at a sensitivity of 10−5 was observed in 35 (80%) of 44 cases. Thirty-two patients discontinued ibrutinib as per protocol (64% of initial series). Twelve patients continued on ibrutinib. The median time on ibrutinib treatment was 29 months, and the median duration of undetectable MRD, achieved in 41 cases, was 60 months, and had not been reached in the 32 cases that stopped ibrutinib as per protocol.
Six patients progressed from the disease between 12 and 72 months of follow-up and three of them eventually died of disease progression. Overall, the PFS and OS rates at 48 months were 86% and 88%, respectively. At the current follow-up, six patients remain on treatment, and up to 13 patients discontinued ibrutinib because of adverse events, including seven associated to ibrutinib with a hemorrhagic cardiac tamponade being the most severe.
Gine E, Medina‐Herrera A, de la Cruz F, et al. Five-year update of the first-line MCL 2015 GELTAMO study prolonged molecular and clinical responses were observed after MRD-driven ibrutinib discontinuation. Abstract #098. Presented at the 17th International Conference on Malignant Lymphoma; June 13-17, 2023; Lugano, Switzerland.