The European Medicines Agency has approved a shorter, 90-minute infusion time for obinutuzumab to be given in combination with chemotherapy in patients with previously treated or untreated advanced follicular lymphoma.
The European Medicines Agency has approved a shorter, 90-minute infusion time for obinutuzumab (Gazyvaro) to be given in combination with chemotherapy in patients with previously treated or untreated advanced follicular lymphoma.1
The decision follows a positive opinion issued by the Committee for Medicinal Products for Human Use, which noted that the regular infusion rate for the drug can range from approximately 3 to 4 hours. It is hypothesized that a shorter infusion period can lead to time savings for patients and could also serve to reduce pressure on healthcare systems.
The approval is also supported by the phase 4 GAZELLE study (NCT03817853), which demonstrated that the safety and efficacy of obinutuzumab proved to be consistent to what had been seen when the agent was given at the normal infusion rate. Notably, no patients reported grade 3 or higher infusion-related reactions during cycle 2 of treatment with the short-duration infusion, and no unexpected safety signals were observed. The decision is also based on findings from other supportive studies evaluating obinutuzumab in patients with follicular lymphoma.
“[Obinutuzumab] has improved outcomes for people with follicular lymphoma, and now has the additional benefit of a shorter infusion time,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche, stated in a press release. “Reducing the amount of time patients need to be in hospital has the potential to improve their treatment experience whilst also increasing efficiency for institutions and healthcare systems.”
The international, open-label, phase 4 GAZELLE trial set out to examine the safety and efficacy of obinutuzumab when given as a 90-minute short duration infusion in patients with previously untreated follicular lymphoma.2 To be eligible for enrollment, patients needed to be at least 18 years of age and have CD20-positive, grade 1 to 3a follicular lymphoma. They also had to have advanced disease that required treatment and an ECOG performance status of 0 to 2. They could not have received prior treatment.
During the induction phase of the trial, participants received a regular infusion of obinutuzumab plus chemotherapy. Obinutuzumab was given intravenously on day 1, 8, and 15 of cycle 1 in accordance with the drug label.
If patients did not experience any grade 3 or higher infusion-related reactions, they went on to receive the short-duration infusion of obinutuzumab plus chemotherapy for cycle 2. If they experienced grade 3 reactions, they went on to receive a regular infusion with chemotherapy for cycle 2; if no grade 3 or higher reactions were observed, they received the short duration infusion in cycle 3. If patients experienced grade 4 infusion-related reactions following cycle 1 of treatment, they discontinued the study.
The primary end point of the trial is incidence of grade 3 or higher infusion-related reactions during cycle 2, and key secondary end points comprised safety, response, progression-free survival, and overall survival.
Data from the end-of-induction analysis were presented during the 2021 ASCO Annual Meeting. At a data cutoff of December 3, 2020, a total of 114 patients were enrolled to the trial and 113 of these patients received study treatment. Specifically, 45.1% of patients received obinutuzumab plus bendamustine as their induction treatment, 38.1% received obinutuzumab plus CHOP, and 16.8% of patients received obinutuzumab plus CVP.
The median age of study participants was 62 years (range, 28-86), 50.4% were male, 70.8% had an ECOG performance status of 0, 61.9% had stage IV disease, and the median number of nodal areas involved was 5 (range, 0-18). Moreover, 51.3% of patients had B symptoms, and 81.4% of patients had an intermediate- or high-risk Follicular Lymphoma International Prognostic Index score.
Data showed that 99.1% of 113 patients reported at least 1 toxicity during the study; 72.6% of patients had grade 3 to 5 adverse effects (AEs) and 23.0% experienced serious AEs. Two patients experienced fatal grade 5 effects in the form of cardiac arrest and aspiration pneumonia; however, both effects were not determined to be related to the study treatment.
The AEs that were most frequently reported during the induction phase of the trial included neutropenia, infusion-related reactions, and nausea. The most common grade 3 to 5 toxicities during induction included neutropenia, leukopenia, and lymphopenia.
Additionally, 62.8% of patients reported an infusion-related reaction during the study and most of these effects occurred during cycle 1; 6.2% of patients reported a grade 3 reaction. Notably, no grade 4 or 5 infusion-related reactions occurred.
Of 110 patients who received obinutuzumab in cycle 2 (106 short duration, 4 regular), 11.8% reported an infusion-related reaction. All reactions reported in cycle 2 were either grade 1 (10.0%) or grade 2 (1.8%). In subsequent treatment cycles, only 1 patient reported a grade 3 or higher infusion-related reaction with the short-duration approach; this patient experienced grade 3 hypertension in cycle 5 of treatment. All other reaction events following short-duration treatment were either grade 1 or 2 in severity.
At the time of data cutoff, all 113 patients had completed induction treatment. Among the 113 patients, 67.3% achieved a complete response (CR) by PET-CT or CT using Lugano 2014, Cheson 2007, or Cheson 1999 criteria; 19.5% had a partial response (PR), 5.3% experienced disease progression, and 8% had missing information. In 57 patients, the CR rate was 80.7% and the PR rate was 15.8% per PET-CT using Lugano 2014 criteria; 3.5% experienced disease progression.
Following the European approval, the label for obinutuzumab is being updated immediately. Moreover, Roche announced plans to launch the short-duration infusion option in the European Union as soon as possible for patients with previously treated and untreated follicular lymphoma.