Measurable Residual Disease Testing Following Nonintensive Chemoimmunotherapy is Predictive of Need for Maintenance Therapy in Previously Untreated Mantle Cell Lymphoma: A Wisconsin Oncology Network Study

Introduction: Obinutuzumab is hypothesized to improve progression-free survival (PFS) combined with bendamustine induction in mantle cell lymphoma (MCL). Measurable-residual disease (MRD) testing may predict benefit from maintenance therapy.

Methods: Adults (≥ 18 years) with untreated MCL ineligible for intensive therapies received 4 to 6 cycles of bendamustine + obinutuzumab (BO) followed by consolidation obinutuzumab (CO). Restaging after CO included MRD assessment by next-generation sequencing of bone marrow aspirate (BMA) and peripheral blood (PB). Maintenance obinutuzumab (MO) was omitted for patients with imaging complete response (CR) and MRD-negativity in PB/BMA. All other patients received 8 cycles MO. Primary endpoint is PFS; secondary endpoints are response rates, overall survival, and estimation of MRD status.

Results: Twenty-one patients enrolled, with median age 70 years and stage IV disease in 95%. Twenty patients completed BO; 10 patients received MO per protocol. Six patients did not complete MO due to progression (n = 4), infection (n = 1) and carcinoma (n = 1). Overall response is 95% (75% CR, 20% partial response). Concordance rate between post-consolidation MRD testing in PB and BMA was 70%. After a median follow-up of 43.9 months, median PFS is 46.5 months. The observed difference between 2-year PFS in groups receiving MO versus observation was not statistically significant (HR 0.45, 95% CI, 0.10-1.91). Most common grade 3/4 toxicities were neutropenia, leukopenia, and infections.

Conclusions: BO is a tolerable induction regimen with higher rates of CR compared with historical rates with bendamustine + rituximab. Omission of MO did not worsen outcomes in patients achieving MRD-negative status after nonintensive induction/consolidation therapy.