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Combining obinutuzumab with DHAP induces MRD negativity in three quarters of untreated mantle cell lymphoma patients

The LyMa-101 trial demonstrated that a combination of obinutuzumab and DHAP is a highly effective induction regimen for younger patients with mantle cell lymphoma. After induction with this regimen, three quarters of patients proved to be minimal residual disease negative in the bone marrow. Longer follow-up is needed to see the ultimate effect of a treatment with obinutuzumab and DHAP followed by an autologous stem cell transplantation and on-demand obinutuzumab maintenance, but the high progression-free and overall survival rates reported at 1 year are very encouraging.


It is well established that prolonged minimal residual disease (MRD) negativity after both induction and autologous stem cell transplantation (ASCT) is a strong independent prognostic marker in mantle cell lymphoma (MCL). The current standard of care for younger MCL patients consists of induction therapy with high-dose aracytine and salt platinum-containing chemotherapy regimen (DHAP) in combination with rituximab followed by ASCT and 3 years of rituximab. Obinutuzumab is a second-generation anti-CD20 monoclonal antibody that was designed to improve the antibody-dependent cell-mediated cytotoxicity seen with rituximab. Obinutuzumab is already being used in the treatment of chronic lymphocytic leukemia and in vitro experiments suggest that obinutuzumab may also provide better anti-MCL activity than rituximab.

Study design and results

The LyMa-101 study is a prospective, multicenter singe-arm phase II trial testing the effect of obinutuzumab in untreated MCL patients under 66 years of age who are eligible for ASCT. The induction regimen in this trial consisted of 4 cycles of obinutuzumab plus DHAP (O-DHAP) before consolidation with ASCT (BEAM conditioning plus obinutuzumab) followed by obinutuzumab maintenance for 3 years and subsequent on-demand obinutuzumab for MRD positive patients. The primary objective of the trial was the MRD negativity rate after 4 cycles of O-DHAP.

In total, the LyMa-101 trial enrolled 86 patients, but one patient withdrew consent before starting treatment. The median age of the patients in the trial was 58 years and 73% was male. Almost all patients in the study had Ann Arbor stage III or IV disease and about one-fifth presented with B-symptoms. Ninety percent of study participants had extra-nodal involvement and 17% presented with a blastoid variant of MCL.

The median follow-up for the presented analysis was 14 months. Fourteen patients out of 85 were not evaluable for MRD, essentially due to purely nodal disease and no detectable MCL clone in peripheral blood or bone marrow. Among the 71 MRD-informative patients, 53 reached MRD negativity in the BM (75%) measured by qPCR. Following induction therapy, 72 patients underwent ASCT and 61 of them started obinutuzumab maintenance. At one year the progression-free survival (PFS) rate was reported at 93.4%, with an overall survival (OS) rate of 96%.


The Lyma-101 trial successfully demonstrated the high efficacy of O-DHAP as induction therapy regimen for patients with MCL yielding an unprecedented high level of MRD negativity. Longer follow-up is needed to evaluate the long-term patient outcome after O-DHAP followed by ASCT and obinutuzumab on-demand maintenance.


Le Gouill S, Beldi-Ferchiou A, Cacheux V, et al. Obinutuzumab plus DHAP followed by autologous stem cell transplantation plus obinutuzumab maintenance provides a high MR response rate in untreated MCL patients, LYMA-101 trial – A LYSA trial. Presented at EHA 2019; abstract S103.

Speaker Steven Le Gouill


Steven Le Gouill, MD, PhD, Nantes University Hospital, Nantes, France


See: Keyslides


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