LyMa-101 trial update: Obinutuzumab for the treatment of mantle cell lymphoma

Mantle cell lymphoma (MCL) is a highly aggressive B-cell lymphoma that has a poor prognosis. The current standard of care involves high-dose cytarabine with rituximab, followed by autologous stem cell transplantation with rituximab maintenance. In the LyMA-101 phase II trial (NCT02896582), obinutuzumab, a glycoengineered anti-CD20 monoclonal antibody, was combined with high-dose cytarabine for the treatment of transplant-eligible patients with MCL. The initial results were reported at the 24th European Hematology Association (EHA) Congress in 2019 and can be found on the Lymphoma Hub here.

The Lymphoma Hub is happy to provide a summary of the updated results, published by Steven Le Gouill and colleagues in Lancet Haematology.¹

Key points

The primary endpoint of the LyMa-101 trial was measurable residual disease (MRD) negativity in the bone marrow after four cycles of obinutuzumab plus dexamethasone, high-dose cytarabine, and cisplatin (DHAP) at the end of induction. The study consisted of three sets of patients:

• Included set: All 86 study patients
• Safety set: 85 patients who received at least one dose of obinutuzumab
• Efficacy set: 73 patients who had at least one dose of obinutuzumab and a MRD bone marrow assessment for clonal IG or BCL1-IGH molecular markers

Median follow-up was 14.6 months (IQR, 10.3−17.2). The primary endpoint was successfully met and the MRD status at the end of induction is reported in Table 1. When this analysis was performed, the only patient who had progressed was MRD negative in the bone marrow and peripheral blood. The 12 patients who were MRD positive did not relapse during the duration of this study.

Table 1. Patient MRD status at the end of induction¹

BM, bone marrow; MRD, measurable residual disease; qPCR, quantitative polymerase chain reaction. *12 BM-positive patients plus two patients who progressed prior to induction and four who were not assessed for MRD stats for reasons other than disease progression.
	Total, % (n = 73)
BM assessed by qPCR	92
BM MRD negative	75
BM MRD positive	16
Patient considered MRD positive*	25

Following induction, 92% of patients in the safety set achieved an overall response (complete response [CR], CR unconfirmed, or partial response), including 61% who achieved a CR or CR unconfirmed.

Anemia (Grade 3, 27%; Grade 4, 4%; n = 85) and neutropenia (Grade 3, 15%; Grade 4, 38%; n = 85) were the most common adverse events. Grade 3 or 4 thrombocytopenia was the main reason for discontinuation of obinutuzumab. In total, 16% of patients in the safety set stopped treatment. Three patients died, but this was not associated with obinutuzumab therapy.

Conclusion

The LyMa-101 trial met its primary outcome and demonstrated the efficacy and tolerability of obinutuzumab with DHAP for the treatment of transplant-eligible patients with MCL. The authors concluded that DHAP plus obinutuzumab has potential as an induction regimen and that MRD negativity may be a helpful surrogate endpoint to predict long-term disease control.