EMA approves shorter infusion time for obinutuzumab for patients with treated/untreated follicular lymphoma

Obinutuzumab is indicated for the treatment of follicular lymphoma (FL) and is known to provide improved therapeutic outcomes by specifically targeting the B-cell marker CD20. The European Medicines Agency (EMA) has recently approved a shorter 90-minute administration time for this drug, which is indicated in combination with chemotherapy for previously treated or untreated advanced FL. The regular infusion rate for obinutuzumab ranges from 3–4 hours, and it is hypothesized that shorter administration time will provide improved treatment experience for patients and will increase efficiency of the healthcare system.¹

The approval is based on the outcome of a number of studies, and especially the phase IV GAZELLE (NCT03817853) study, which evaluated the safety and efficacy of obinutuzumab in patients with previously untreated FL when the drug was administered as a 90-minute infusion.

Eligible patients were ≥ 18 years, CD20-positive, and had untreated Grade 1–2a FL with Eastern Cooperative Oncology Group (ECOG) performance 0–2. The participants received obinutuzumab along with chemotherapy during the induction phase of the study. A regular infusion of obinutuzumab was administrated intravenously on Days 1, 8, and 15.

Decision on further treatment cycles was made based on treatment-emergent adverse events (TEAEs):

• Patients who did not have ≥ Grade 3 TEAEs after Cycle 1 of treatment received short-duration administration of obinutuzumab along with chemotherapy for Cycle 2.
• Patients who experienced Grade 3 TEAEs in Cycle 1 continued regular obinutuzumab infusion and chemotherapy in Cycle 2, and short-duration infusion of obinutuzumab in Cycle 3.
• Patients who experienced Grade 4 TEAEs discontinued the study.

Primary endpoint: ≥ Grade 3 TEAEs during Cycle 2.

Key secondary endpoints: Safety, response, progression-free survival (PFS), and overall survival (OS).

This study showed consistent safety and efficacy of obinutuzumab when the drug was given at the normal infusion rate. No patients reported ≥ Grade 3 TEAEs during Cycle 2 with the short-duration infusion.

The study was further extended for the end of induction analysis. Patients (n = 113) received obinutuzumab in combination with either bendamustine (45.1%), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone; 38.1%) or CVP (cyclophosphamide, vincristine, and prednisone; 16.8%).

It was observed that 99.1% of patients experienced at least one toxicity; Grade 3–5 TEAEs were observed in 72.6% of patients, and serious TEAEs were seen in 23% of patients. Grade 5 fatal events (i.e., cardiac arrest and aspiration pneumonia) were reported in two patients, but these were not related to the treatment.

The most frequently occurring TEAEs were neutropenia, infusion-related reactions, and nausea. The most common Grade 3–5 TEAEs were neutropenia, leukopenia, and lymphopenia.

During Cycle 1, infusion-related reactions were reported in 62.8% of the study population; Grade 3 reactions were reported in 6.2% of patients. There were no reports for Grade 4/5 infusion-related reactions.

In Cycle 2, 11.8% of the population reported an infusion-related Grade 1 or 2 reaction (106 patients had the short duration infusion, and four patients had the regular infusion of obinutuzumab).

In subsequent treatment cycles, there was just one reported Grade ≥ 3 infusion-related reaction for the short duration administration approach.

At the end of induction, 67.3% of patients achieved complete response (CR) and 19.5% obtained partial response (PR). Furthermore, disease progression was identified in 5.3% patients and 8% had missing information.

Following the EMA approval, the option for the short-duration infusion treatment will be launched as soon as possible for patients with previously treated and untreated FL.