Atlanta, GA—Among patients with untreated follicular lymphoma, 75% achieved complete responses with the 3-drug combination of atezolizumab (Tecentriq), obinutuzumab (Gazyva), and bendamustine (Treanda), results of a small, preliminary clinical trial reported at ASH 2017 showed.
The regimen achieved an overall response rate (ORR) of 85% in 40 evaluable patients. Although active, the regimen caused substantial toxicity, and more than 50% of the patients had grade 3 or 4 adverse events that led to treatment interruption.
The 3-drug combination “resulted in encouraging end-of-induction activity in previously untreated patients,” said Anas Younes, MD, Chief, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York City.
Acknowledging the preliminary nature of the study, he added, “Longer follow-up is needed to make a more comprehensive benefit–risk evaluation of this combination and to perform an analysis of biomarkers.”
The response rate with the 3-drug combination was similar to that observed in the large, randomized, phase 3 GALLIUM trial that compared rituximab (Rituxan)-based induction chemotherapy with obinutuzumab-based induction in patients with untreated follicular lymphoma (Marcus R, et al. N Engl J Med. 2017;377:1331-1344). The ORRs in GALLIUM were 87% to 88% in both treatment groups. Despite the high initial response rates, including complete responses, the disease eventually relapsed in most patients with follicular lymphoma, Dr Younes noted. As a result, investigators continue to evaluate therapies that may achieve more durable responses or offer effective options for relapsed disease.
“Atezolizumab targets PD-L1 and has a complementary mechanism of action to obinutuzumab and has the potential to improve outcomes when added to obinutuzumab-based chemotherapy,” he said.
Eligibility criteria for this preliminary study included untreated grade 1 to 3a follicular lymphoma or relapsed or refractory disease. Patients received induction therapy with all 3 drugs, and patients who achieved a complete or partial remission received maintenance therapy with obinutuzumab and atezolizumab for as long as 24 months.
The study included a 6-patient safety run-in phase, and patients with relapsed or refractory disease were eligible to participate only in the safety evaluation. The primary end point was complete response at the end of induction therapy, as determined by positron emission tomography or computed tomography assessment. The secondary end points included investigator-assessed complete response at the end of induction treatment using modified Lugano 2014 criteria and additional assessments of complete response, using different criteria to define complete response.
The investigators enrolled 42 patients, 2 of whom had relapsed or refractory disease. The efficacy analysis included only the 40 patients with previously untreated follicular lymphoma. At data cutoff, 35 patients continued to use maintenance therapy, with median duration of 5.5 months, including 8 patients who received maintenance therapy for at least 12 months.
Overall, 93% of the patients had Ann Arbor stage III or IV disease. More than 70% of the patients had grade 2 or 3a disease, and Follicular Lymphoma International Prognostic Index risk status was low in 24%, intermediate in 43%, and high in 33% of patients. Approximately 20% of the patients had bulky disease (>7 cm), and approximately 50% had bone marrow infiltration.
By modified Lugano criteria, the ORR at the end of induction was 85% by independent review and 95% by investigator assessment.
In addition to a 57% rate of grade 3 or 4 adverse events, 29% of patients had serious adverse events, and 10% of patients discontinued treatment as a result. Furthermore, 10% of patients required dose reduction of bendamustine because of associated adverse events, and 57% required dose interruption.
During induction, the most common grade 3 or 4 hematologic adverse events were neutropenia in 11 patients and thrombocytopenia in 2 patients. In addition, grade 3 or 4 lipase elevation occurred in 3 patients during induction.
Seven patients had a total of 12 adverse events of special interest during induction therapy, including 3 with grade 1 or 2 and 1 case each of grade 4 increase in lipase, grade 2 rash, grade 4 myocarditis, and grade 1 bronchiolitis.
Two patients died—1 from cardiac arrest associated with severe myocarditis and bronchiolitis and 1 from unknown cause.