ASH 2023: Loncastuximab for High-Risk Relapsed/Refractory Follicular Lymphoma

In the most recent conference of the American Society of Hematology, Dr. Juan Alderuccio and colleagues, from the Sylvester Comprehensive Cancer Center at the University of Miami, presented the initial results of a phase II clinical trial evaluating an antibody-drug mixture plus rituximab for high-risk follicular lymphoma patients. They observed high effectiveness and tolerability in their study patients. Our HealthTree team had the opportunity to interview Dr. Alderuccio about this study. Watch the video here or read the following summary.

Follicular Lymphoma

Follicular lymphoma is considered a chronic illness by some due to a generally favorable prognosis with 10-year overall survival rates up to 80% according to published studies.

The management of follicular lymphoma depends on the disease stage. Options available include observation until progression (disease growth), radiotherapy, single-agent rituximab, chemotherapy, immunochemotherapy, in addition to various combinations of these drugs. Currently, there is no standard approach to treat patients with relapsed/refractory follicular lymphoma (disease that has either stopped responding to treatment or has returned after treatment).

Loncastuximab tesirine (Zynlonta) is an antibody-drug mixture approved for relapsed/refractory diffuse large B cell lymphoma (DLBCL). The drug has proven effective in a small group of patients with follicular lymphoma, with an overall response rate of 78%.

The combination of loncastuximab tesirine and rituximab has been studied in a preclinical setting showing synergistic effects. Dr. Alderuccio and his fellows presented the initial results of the first clinical trial evaluating this combination in patients with relapsed/refractory follicular lymphoma.

Trial Design

This clinical trial included patients who met the following criteria:

• Patients with high-risk follicular lymphoma, defined as disease growth within 24 months from start of therapy or by using GELF Criteria (considers clinical assessments and laboratory measurements).
• Previously treated with at least one complete cycle of an approved standard therapy.

Enrollment included 33 patients. The majority of participants were over 65 years old and presented with stage III or IV follicular lymphoma at the time of relapse, accompanied by a high tumor burden. These patients received loncastuximab/rituximab according to the study protocol.

The initial response assessment was conducted at week 12, followed by three more doses of loncastuximab tesirine and one more dose of rituximab. An additional response assessment was performed at week 21. Patients achieving a complete response, indicating no evidence of disease on PET-CT at week 21, discontinued loncastuximab tesirine and received two more doses of rituximab. Those with partial responses, indicating some reduction of lymphoma signs/symptoms, continued both drugs for an additional 18 weeks.

Trial Results

Researchers evaluated complete response (full reduction of lymphoma signs/symptoms) by week 12 as the main result. Overall response (combination of partial response and complete response) and side effects were also evaluated.

Upon concluding the treatment, a PET-CT scan was performed, demonstrating some remarkable results. Efficacy was evaluated in 27 patients. As of November 26, 2023, 23 patients (85.2%) achieved a complete response (full reduction of lymphoma signs/symptoms), 3 patients (11.1%) achieved partial response (some reduction of lymphoma signs/symptoms), and one patient developed progressive disease. This resulted in an overall response of 96.3%. The median time to overall response was 11.9 weeks.

Most side effects were grade 1 (mild). The most common were increased liver enzymes (lab values called AST and ALT) in around 40% of patients, high blood sugar (40%), rash (37%), fatigue (34%), and edema (fluid accumulation in the tissues managed by diuretics). Other common grade one toxicities included low blood counts. Importantly, none of the patients required blood transfusions during the study and no treatment-related deaths occurred during the study.

Loncastuximab Demonstrated Clinically Meaningful Benefit

Short term loncastuximab with rituximab showed significant complete response rates and overall response rates in relapsed/refractory follicular lymphoma. The safety was similar to prior studies in lymphoma, with no new concerns. Thus, this combination showed clinically meaningful benefits.

Of note, this is an ongoing study currently recruiting patients.

Dr. Alderuccio was pleased to announce that after these results, the next step is to develop a multicenter trial to expand the current cohort and confirm the safety and efficacy observed in this single institution clinical trial. This trial is expected for early 2024.