Antibody-Drug Conjugate Succeeds in High-Risk R/R Follicular Lymphoma

Follicular Lymphoma: Follicular LymphomaHigh numbers of durable complete remissions were observed in a Phase II study in the subset of patients with relapsed or refractory follicular lymphoma at high risk of relapse. Findings were reported at the 65th ASH Annual Meeting and Exposition held in San Diego. First author Juan Pablo Alderuccio, MD, Associate Professor of Medicine in the Sylvester Comprehensive Cancer Center at the University of Miami School of Medicine, told the conference that treatment with the antibody-drug conjugate (ADC) loncastuximab tesirine combined with the CD20 protein-targeted monoclonal antibody rituximab brought a high rate of complete metabolic responses among patients satisfying the Groupe d'Etude des Lymphomas Folliculaires (GELF) risk criteria and in those with disease progression within 24 months (POD24). With no standard-of-care treatment for patients who have high-risk relapsed/refractory follicular lymphoma, the study findings suggested that the ADC could become an appealing option. “Hopefully, this will be a treatment option for patients with relapsed/refractory follicular lymphoma. The attractive part of this regimen is that it is of fixed duration, so patients will know for how long we'll treat. Also, this is an outpatient treatment, so a patient doesn't need to be hospitalized for therapy,” Alderuccio told Oncology Times. Study Details The tumor-seeking payload of the ADC loncastuximab is comprised of a humanized anti-CD19 antibody conjugated to a pyrrolobenzodiazepine dimer cytotoxin. It was currently approved in the U.S. for patients with relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy, Alderuccio noted. “Specifically in follicular lymphoma, there was significant activity in the Phase I [study] (of 14 patients) with the overall response rate of 78.6 percent and the CR rate of 64.3 percent,” he said. These encouraging responses prompted the team to expand the cohort in follicular lymphoma. In the Phase II cohort of 33 patients, most of the patients received a median of one line of therapy and a quarter of them had more than three lines of therapy, Alderuccio said. The most common prior treatment was R-CHOP, followed by bendamustine with rituximab and single-agent rituximab. Further therapy could depend on the prior therapy, he noted. For patients with POD24, stem cell transplantation and even CAR T-cell therapy were options, he said. “But those treatments require hospitalization and can be associated with significant toxicity. This treatment with loncastuximab is an outpatient infusion of 45 minutes and similarly with rituximab. So, we were aiming to develop a highly effective, safe, outpatient treatment option for this population.” The Phase II part of the study exceeded the response rates that had been achieved in the Phase I stage with single-agent loncastuximab. “Overall, across all 27 patients who were assessed for response, we observed an overall response rate of 96.3 percent with a complete response rate of 85.2 percent.” Among the patients with POD24, the response rate was even higher, Alderuccio said. “When we look at those 16 patients with POD24, the response rate was 100 percent with a complete metabolic response rate of 87.5 percent.” When he was asked about the long-term outlook for these patients, he said those who had received the new combination had done well so far. “The 6-month progression-free survival has been 92.3 percent with 6-month overall survival of 96 percent,” he said, regarding these data as “highly promising.” Most adverse events were Grade 1, including rash, increase in liver enzymes, and fatigue. There were no new safety signals, the researchers stated. “Based on these results that are highly encouraging and support the use of loncastuximab with rituximab in patients with relapsed/refractory follicular lymphoma, we are now expanding this clinical trial to a multi-center study aiming to enroll 100 patients confirming our initial observations of efficacy and toxicity in this population,” Alderuccio concluded. Peter M. Goodwin is a contributing writer.