Vials and a syringe

In a phase 3 trial, subcutaneous (SC) and intravenous (IV) rituximab produced comparable results as part of a first-line treatment regimen for follicular lymphoma (FL).

Overall response rates (ORR) were similar in patients who received SC rituximab and those who received IV rituximab, first in combination with chemotherapy and then alone as maintenance therapy.

Although patients who received SC rituximab had administration-related reactions that weren’t observed in the IV rituximab group, these events were largely mild-to-moderate local injection-site reactions.

Andrew Davies, PhD, of the University of Southampton in the UK, and his colleagues reported these results in The Lancet Haematology.

Data from stage 1 of this study, known as SABRINA, were previously published in The Lancet Oncology. The current publication includes stage 2 data.

The study was funded by Roche, which markets rituximab as Rituxan and MabThera.

The trial enrolled 410 patients with previously untreated, grade 1-3a, CD20-positive FL.

Patients were randomized to receive IV rituximab at 375 mg/m² (n=205) or SC rituximab at 1400 mg (n=205) plus chemotherapy.

Chemotherapy consisted of 6 to 8 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) every 3 weeks during induction.

Patients then received rituximab maintenance every 8 weeks.

The researchers said baseline characteristics were balanced between the treatment arms, although there were more females in the SC arm than the IV arm—120 (59%) and 99 (48%), respectively.

Efficacy

In stage 1 of this study, the primary endpoint was the ratio of observed rituximab serum trough concentrations (C_trough) between the treatment arms at cycle 7.

The results suggested SC rituximab was non-inferior to the IV formulation. The geometric mean C_trough was 83.13 μg/mL in the IV arm and 134.58 μg/mL in the SC arm (ratio=1.62).

In stage 2, the primary endpoint was efficacy, or ORR, at the end of induction based on the researchers’ assessments and confirmed by an independent review panel of radiologists.

At the end of induction, the ORR was 84.9% (174/205) in the IV arm and 84.4% (173/205) in the SC arm. The complete response rate was 32.2% (n=66) in both arms.

At the end of maintenance therapy, the ORR was 78.1% (139/178) in the IV arm and 77.9% (134/172) in the SC arm. The complete response rates were 56.2% (n=100) and 50.6% (n=87), respectively.

At a median follow-up of 37 months, there was no significant difference between the arms with regard to progression-free survival (hazard ratio[HR]=0.84), event-free survival (HR=0.91), or overall survival (HR=0.81).

Safety

The incidence of adverse events (AEs) was similar between the treatment arms—95% in the IV arm and 96% in the SC arm. The incidence of grade 3 or higher AEs was 55% and 56%, respectively, and the incidence of serious AEs was 34% and 37%, respectively.

Overall, the most common AEs were gastrointestinal disorders (60% in the IV arm and 66% in the SC arm), infections and infestations (64% and 67%, respectively), and general or administration site conditions (50% and 60%, respectively).

Administration-related reactions were more common in the SC arm than the IV arm—48% and 35%, respectively. The most common of these reactions were chills (7%) and pruritus (6%) in the IV arm and injection-site erythema (11%), pruritus (6%), rash (5%), and injection-site pain (5%) in the SC arm.

Neutropenia was the most common grade 3 or higher AE, occurring in 34% of patients in the IV arm and 37% in the SC arm. Febrile neutropenia was the most frequent serious AE, occurring in 5% and 6%, respectively.

The researchers said these results suggest the SC formulation of rituximab has similar efficacy and a similar safety profile as IV rituximab in the first-line treatment of FL.

IV and SC rituximab produce similar results in FL