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No evidence supporting rituximab maintenance beyond two years in patients with relapsed or refractory indolent non-hodgkin lymphoma

Data from the randomised, phase III MabCute trial presented during EHA 2019 do not provide evidence supporting maintenance therapy with subcutaneous rituximab beyond two years in patients with relapsed/refractory indolent non-hodgkin lymphoma (R/R iNHL) who were treated with rituximab-based induction therapy and two years of rituximab maintenance. The safety profile of the subcutaneous formulation of rituximab (R-SC) was consistent with the known safety profile of rituximab.


The current standard of care for patients with iNHL consists of induction treatment with a combination of chemotherapy and rituximab, followed by rituximab maintenance. However, the optimal duration of this maintenance phase is unknown. MabCute is an international, randomised, open-label Phase III trial evaluating the efficacy and safety of prolonging maintenance therapy with R-SC after standard R-SC-based induction and two years of rituximab maintenance in R/R iNHL patients.

Study design

In order to be eligible for the study, patients had to be 18 years or older and have R/R CD20+ follicular lymphoma (grade 1, 2 or 3a) or another form of iNHL (Waldenström’s macroglobulinemia, lymphoplasmacytic lymphoma or marginal zone lymphoma). In the induction phase of the trial, all patients received 8 cycles of R-SC (375mg/m2 IV in cycle 1 then 1400 mg SC in cycles 2–8) in combination with 6–8 cycles of chemotherapy. After induction therapy, patients with a complete or partial response (CR/PR) were treated with 2 years of R-SC maintenance (12 cycles of 1400 mg R-SC every 8 weeks). After that period, patients with a PR or CR were randomised to prolonged maintenance therapy with R-SC or observation. The primary endpoint of the study was PFS from randomization (PFSrand).


Of the 692 patients who started induction therapy, 505 continued to the first maintenance phase and of those, 276 were randomised to prolonged maintenance or observation (N= 138 in both arms). Patient and disease characteristics were generally well balanced between both treatment arms. The median age of patients in the study was 64 years and about 60% had Ann Arbor stage IV disease at diagnosis. A third of patients had a high FLIPI score and 43% presented with bone marrow involvement.

At the time of the analysis only 46 PFSrand events were observed in the randomised groups: 19 in the prolonged maintenance arm and 27 among patients in the observation arm.  PFSrand between the two treatment arms was not statistically significant (p= 0.410, stratified log rank test). To achieve a statistical power of 80%, 129 events would have been needed. At the end of the study, 10 patients in the maintenance group and 8 patients in the observation group had died. As such, there was not enough information to draw any conclusions with respect to OS. The ORR (CR/PR) at end of the induction therapy was 84.7%, and 77 of 357 patients with a PR at the end of induction achieved a CR by end of initial maintenance, corresponding to a conversion rate of 21.6%.

The incidence of grade ≥3 adverse events (AEs) (34.8% vs. 29.0%) was similar for prolonged maintenance and observation, as was the case for the rate of serious AEs (22.5% vs. 23.2%). The most common grade ≥3 AEs with prolonged maintenance and observation were neutropenia (8.7% vs. 5.8%), pneumonia (5.1% vs. 2.9%) and hypertension (2.2% vs. 0%). The most common serious AE with prolonged R-SC maintenance was pneumonia, which was seen in 5.8% of patients (vs. 2.9% with observation).


The results of the MabCute trial do not suggest that there is a benefit of prolonging the maintenance therapy with R-SC beyond two years in patients with R/R iNHL. However, the event rate in this trial was very low making it difficult to formulate firm conclusions. In this trial a subcutaneous formulation of rituximab was used, but the reported safety profile was in line with the known safety profile of rituximab. Furthermore, prolonged maintenance therapy with rituximab did not result in additional toxicity.


Rule S, Gois W, Briones J, et al. Efficacy and safety of prolonged maintenance with subcutaneous rituximab in patients with relapsed or refractory indolent non-hodgkin lymphoma: results of the phase III MabCute trial. Presented at EHA 2019; abstract S101.

Speaker Simon Rule


Simon Rule, MD, PhD, Derriford Hospital Plymouth Hospitals NHS Trust, Plymouth, UK


See: Keyslides


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