Immunotherapy combination induces ‘robust’ responses in high-risk follicular lymphoma
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Key takeaways:
- Most patients in the high-risk study population had some response to treatment.
- All high-grade treatment-related adverse events resolved through supportive care.
SAN DIEGO — Limited duration loncastuximab tesirine in addition to rituximab appeared well tolerated and highly effective for relapsed or refractory follicular lymphoma, according to data presented at ASH Annual Meeting and Exposition.
“We observed that limited duration loncastuximab with rituximab drives significant complete metabolic response rate in patients with relapsed or refractory follicular lymphoma with high-tumor burden and [progression of disease within 24 months (POD24)],” Juan Pablo Alderuccio, MD, associate professor of medicine in the division of hematology at Sylvester Comprehensive Cancer Center, told Healio. “Complete metabolic responses appear robust, similar to prior observations from the phase 1 study, and the safety profile was consistent with prior studies in large B-cell lymphoma, with no new safety signals.”
Background and methodology
Patients with relapsed or refractory follicular lymphoma currently have no standard-of-care treatment option, with worse prognosis among patients who demonstrate POD24 from front-line immunochemotherapy.
Loncastuximab tesirine (Zynlonta, ADC Therapeutics) is an antibody-drug conjugate comprising a monoclonal antibody directed against CD19 and a DNA cross-linking pyrrolobenzodiazepine.
Prior preclinical data has shown synergistic activity between rituximab-induced cytotoxicity and loncastuximab, according to background information provided by study investigators.
Alderuccio and colleagues conducted a single-institution, investigator-initiated study to evaluate the combination of loncastuximab tesirine and rituximab (Rituxan; Genentech, Biogen) in certain patients with follicular lymphoma.
They enrolled 26 adults (median age, 86 years; range, 47-89; 54% women; 77% with advanced-stage disease) with relapsed or refractory follicular lymphoma who had previously been treated with at least one line of systemic therapy.
Treatment included 21 weeks of therapy with four weekly IV doses of 375 mg/m2 rituximab followed by one dose every 8 weeks for a total of five doses, plus IV doses of 0.15 mg/kg loncastuximab every 3 weeks for two doses, followed by 0.075 mg/kg every 3 weeks for a total of seven doses.
Patients who achieved complete remission by week 21 discontinued loncastuximab and received two more doses of rituximab every 8 weeks. Researchers required premedication with 4 mg dexamethasone twice daily for 3 days with loncastuximab.
Complete response by week 12 served as the study’s primary endpoint.
Results
Researchers observed complete response in seven of the initial 10 patients who met prespecified criteria to proceed to stage 2. Among 21 patients evaluable for response, researchers noted an ORR at week 12 of 95.2% (complete response rate of 66.7%, partial response rate of 28.6%).
All patients with a complete response and four of the six with a partial response improved to complete response at week 21, for a best complete response rate of 86% (n = 18 patients).
The most common grade 1 adverse events included alkaline-phosphatase (48%), alanine aminotransferase (44%) and aspartate aminotransferase (36%) elevation; maculo-papular rash (44%); fatigue (28%); thrombocytopenia (28%); photosensitivity (28%); leg edema (24%) and anasarca (20%). Grade 2 adverse events included alkaline phosphatase elevation (12%), anasarca (8%) and leg edema (4%), whereas grade 3 adverse events included neutropenia (8%) and one case each of cellulitis and pleural effusion.
Researchers noted neutropenia as the only grade 4 adverse event in a patient after chimeric antigen receptor T-cell therapy. No treatment-related deaths occurred during the study, and all toxicities resolved with supportive management.
Next steps
The results, according to researchers, provide promise for a new treatment method for certain patients with follicular lymphoma, for which no standard-of-care treatment currently exists.
“The most important take-home message is that loncastuximab with rituximab demonstrated clinically meaningful benefit in patients with relapsed or refractory follicular lymphoma, supporting this combination as a new treatment option,” Alderuccio told Healio. “We are now in the process of expanding the study cohort to 100 patients and transitioning the study to a multicenter clinical trial in order to confirm initial safety and efficacy.
“Hopefully this treatment program will be available to every patient with relapsed or refractory follicular lymphoma soon,” he added.
For more information:
Juan Pablo Alderuccio, MD, can be reached at jalderuccio@med.miami.edu.
Collapse
Alderuccio JP, et al. Abstract 984. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2023; San Diego.
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