Loncastuximab Combo Shows Results in High-Risk Follicular Lymphoma

Follicular LymphomaA combination of loncastuximab tesirine and rituximab in patients with high-risk relapsed/refractory follicular lymphoma (FL) led to robust and durable complete metabolic responses (CMR) in a high proportion of patients with encouraging survival data, demonstrating the potential of this treatment approach in improving outcomes for patients with high-risk disease. In a single-institution, Phase II, investigator-initiated study of 39 FL patients receiving loncastuximab and rituximab, of 35 evaluable patients, the objective response rate at Week 12 was 97.1 percent with a CMR rate of 68.6 percent. All patients who achieved a CMR maintained their response. The response of four of 10 patients with partial metabolic response improved to CMR at Week 21, showing a best CMR rate of 80 percent. Baseline FL bone marrow involvement resolved in all 10 patients at Week 12 reassessment. At a median follow-up of 15.6 months, patients had a 12-month progression-free survival (PFS) rate of 94.2 percent and an overall survival (OS) rate of 93.3 percent. At 18 months, the PFS rate was 90.1 percent and the OS rate was 93.3 percent. “The prognosis for patients with relapsed or refractory follicular lymphoma has significantly improved over the last couple of years,” said lead author Juan Alderuccio, MD, Associate Professor of Medicine at the University of Miami Miller School of Medicine. “We have several options and our goal now is to keep high efficacy, but also decrease toxicity. Even in patients with high-risk disease, this [combination] treatment is able to overcome adverse prognosis factors.” Study Details At the 66th ASH Annual Meeting & Exhibition, Alderuccio presented information about a Phase II clinical trial evaluating loncastuximab with rituximab in relapsed/refractory FL based on encouraging results from a Phase I study and preclinical data demonstrating synergistic activity between both agents. The researchers enrolled 39 adult patients previously treated with one or more lines of systemic therapy who presented with progression of disease within 24 months (POD24) or GELF criteria. The initial 21 weeks of therapy consisted of 4 weekly doses of rituximab intravenously 375 mg/m2 followed by 1 dose every 8 weeks for a total of 5 doses in combination with loncastuximab intravenously 0.15 mg/kg every 3 weeks for 2 doses followed by 0.075 mg/kg every 3 weeks for a total of 7 doses. Premedication with dexamethasone 4 mg twice daily for 3 days was required. Patients achieving CMR at Week 21 discontinued loncastuximab and received two more doses of rituximab every 8 weeks. No prophylaxis was required per study protocol. Patients' median age was 68 years and most were men (53.8%) with advanced-stage (82%), high-disease burden by GELF criteria (87.2%), and/or POD24 after frontline immunochemotherapy (51.3%). The median FLIPI score was 3 with most patients allocated to the high-risk group (61.5%). Median lines of prior therapy were 1 with R-CHOP, the most common first-line therapy (56.5%), followed by bendamustine with rituximab (25.6%); single-agent rituximab (15.3%); and fludarabine, mitoxantrone, and dexamethasone (2.6%). The median PFS was not reached. On a positive note, Alderuccio said the antibody combination showed similar response rates in patients with POD24 and those without. Only one patient had no response to the treatment. Two patients with disease progression on imaging had biopsy-proven transformation to diffuse large B-cell lymphoma and died from aggressive lymphoma, and one patient had relapsed FL and is currently on observation due to asymptomatic and localized disease. The most common treated-emergent adverse events were neutropenia (53.8%), alkaline phosphatase elevation (53.8%), anemia (46.1%), maculopapular rash (46.1%), fatigue (43.5%), aspartate aminotransferase (38.4%), and alanine aminotransferase elevation (38.4 %). The only adverse event of Grade 3 or higher was neutropenia. There was one case each of Grade 2 urinary tract infection and fluid accumulation. There were no treatment-related deaths. Because so many patients saw a complete response by 12 weeks of treatment, the researchers recently reduced the treatment length from 10 to 6 months. They hope the relatively short course of treatment combined with low toxicity will mean patients can tolerate and complete the therapy without difficulty. “Our study supports this combination as a new treatment option in FL,” Alderuccio said. A multicenter expansion cohort is ongoing with a planned enrollment of 100 patients. Mark L. Fuerst is a contributing writer.