The AUGMENT Study with Lenalidomide and Rituximab in Patients with Relapsed/Refractory iNHL

Oral presentation by Dr. John P. Leonard

Immunochemotherapy followed by rituximab maintenance is the standard of care in previously untreated patients with symptomatic follicular lymphoma (FL). Bendamustine and rituximab followed by 2 years of rituximab maintenance is the most commonly used initial therapy in Canada. Inevitably, most patients will relapse and require further therapy. Currently, there is no standard of care for relapsed/refractory patients. Typically, patients may receive another course of immunochemotherapy, with the choice of chemotherapy dependent on prior treatment and responsiveness (cyclophosphamide, vincristine, and prednisone; cyclophosphamide, doxorubicin, vincristine, and prednisolone; fludarabine; or bendamustine), and the choice of antibody dependent on prior response to rituximab (obinutuzumab combined with chemotherapy can be considered for patients with rituximab refractory disease). Recently, the phase III RELEVANCE trial evaluated the efficacy of lenalidomide and rituximab (R2) compared with immunochemotherapy in patients with untreated FL. While, this trial did not demonstrate the superiority of R2, it did establish R2 as an effective therapy for FL, as the outcome was similar to patients receiving immunochemotherapy.

The AUGMENT trial is a multicentre, double-blind, randomized phase III study of Rversus rituximab and placebo in patients with relapsed/refractory FL grade 1–3a or marginal cell lymphoma (MZL) not refractory to rituximab. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), complete response (CR), duration of response (DOR), time-to-next anti-lymphoma treatment (TTNLT), overall survival (OS), and safety.

A total of 358 patients were randomized with a median age of 63 years. Of the total patient population, 82% had FL and 18% had MZL. At median follow-up of 28.3 months, the study met its primary endpoint of PFS with an HR of 0.46 (95% CI: 0.34–0.62; <0.0001) in favour of R2; median PFS was 39.4 months for Rversus 14.1 months for rituximab. Independent review committee–assessed ORR for Rwas 78% versus 53% for rituximab (<0.0001), whereas CR was 34% and 18%, respectively (= 0.001). DOR and TTNLT also favoured R2. There was no difference in OS between the arms. Adverse events (AEs; all grade) were more common in the Rarm, including infections, cutaneous reactions, constipation, thrombocytopenia, and tumour flare reaction. More frequent grade 3/4 AEs in the Rversus rituximab arm were primarily neutropenia and leukopenia. Seventy-one percent of Rpatients completed all 12 cycles of planned treatment versus 61% of rituximab, with progression being the leading reason for discontinuation. Dose reductions of lenalidomide were required in a proportion of patients, with only 55% of patients completing treatment at the 20 mg dose.

Results of the AUGMENT trial further confirm R2 as an effective therapy for FL. The demonstrated benefit of R2 over rituximab monotherapy is not surprising, and has been previously shown in a randomized phase II trial. Nonetheless, the high response rate and prolonged PFS associated with R2 in this setting, along with a reasonable toxicity profile, make it a desirable treatment option that will undoubtedly further improve outcomes for patients with FL. Hopefully this trial will be sufficient to enable approval and funding in Canada in the near future.

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