In a prospective, open-label, single-arm phase 2 clinical trial, the addition of obinutuzumab to a dexamethasone, high-dose cytarabine, and cisplatin (DHAP) regimen showed promising activity and tolerability in patients with mantle cell lymphoma (MCL) with transplant-eligible status. The results of the trial were published in The Lancet Haematology.
The open-label, single-arm LyMa-101 trial (ClinicalTrials.gov Identifier: NCT02896582) recruited patients from 28 hospitals throughout France who had previously untreated MCL and were eligible for autologous stem-cell transplantation. Patients were treated with DHAP plus 4 cycles of obinutuzumab prior to transplantation. Obinutuzumab was also administered as maintenance therapy for 3 years, with additional maintenance based on minimal residual disease (MRD) status.
Bone marrow (BM) MRD status following induction, evaluated using quantitative polymerase chain reaction, was the primary study outcome. The MRD-negativity threshold for determining the effectiveness of obinutuzumab added to DHAP was 70% of the intent-to-treat population.
Of 86 enrolled patients, induction was completed in 81 participants. Autologous stem-cell transplantation was completed by 73 patients, and maintenance was initiated for 69 patients. The median patient age for the enrolled population was 58 years, and 91% of patients had stage IV disease at diagnosis.
In an efficacy population of 73 patients, the rate of BM MRD-negativity following induction was 75% (55 patients). Remaining patients included 12 patients with BM MRD-positive status, 2 patients who demonstrated progression, and 4 who were not successfully evaluated for BM MRD status. When considering only the patients who were successfully assessed for BM MRD status, 82% were BM MRD-negative. This compares with a 95% rate of MRD-negativity in the peripheral blood among tested patients.
In a safety population of 85 patients who received 1 or more doses of obinutuzumab, grade 3 anemia was reported in 31% and grade 4 anemia in 4%. Grade 3 neutropenia was reported in 15% and grade 4 neutropenia in 38%. A total of 73% of patients had grade 4 adverse events. Treatment-related fatalities reportedly did not occur, but 4% of enrolled patients died for reasons considered unrelated to the use of obinutuzumab.
“In conclusion, the LyMa-101 trial achieved its primary endpoint and showed the potential activity of obinutuzumab plus DHAP as induction chemotherapy, with bone marrow minimal residual disease negativity potentially predicting long-term disease control,” the study investigators concluded.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Le Gouill S, Beldi-Ferchiou A, Alcantara M, et al. Molecular response after obinutuzumab plus high-dose cytarabine induction for transplant-eligible patients with untreated mantle cell lymphoma (LyMa-101): a phase 2 trial of the LYSA group. Lancet Haematol. Published online September 21, 2020. doi:10.1016/S2352-3026(20)30291-X