CD19 Antibody Targeting With MOR208 Is Active in DLBCL
Single-agent MOR208 showed promising activity with long-lasting responses in aggressive and indolent NHL subtypes, including in rituximab-refractory disease.
Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) had promising responses to treatment with MOR208, an Fc-engineered, humanized, CD19 antibody, according to the results of a phase IIa study published in Annals of Oncology. “Single-agent MOR208 showed promising activity with long-lasting responses in aggressive and indolent NHL subtypes, including in patients with rituximab refractory disease,” wrote Wojciech Jurczak, MD, PhD, of the department of hematology, Jagiellonian University, Krakow, Poland, and colleagues. “Based on these data, and the favorable safety and tolerability of MOR208, further clinical development of combination therapy with MOR208 is now being undertaken in patients with B-cell malignancies.”
In their report, the authors noted CD19 is broadly expressed across a variety of B-cell malignancies, and it is an attractive target for treatment since its expression has been shown to be preserved during lymphoma treatment.
The study included 92 patients with relapsed or refractory B-cell NHL that had progressed after one or more prior rituximab-containing regimens. Patients were assigned to treatment cohorts based on disease subtype: DLBCL (n = 35), FL (n = 34), other indolent non-Hodgkin lymphoma (NHL; n = 11), and mantle cell lymphoma (n = 12).
Patients received 12 mg/kg intravenous MOR208 weekly for 8 weeks. Patients with stable disease could add an additional 4 weeks of therapy. Any patients with partial or complete response at 12 weeks could extend MOR208 until disease progression.
Responses occurred in patients with DLBCL (27%), FL (29%), and indolent NHL (27%). Several patients in each subgroup had responses that lasted longer than 1 year (5 of 9 for DLBCL, 4 of 9 in FL, and 2 of 3 in indolent NHL). The median duration of response was 20.1 months. Overall, 9 patients have experienced ongoing responses, including 5 patients with a response lasting longer than 2 years.
“Notably, responses were seen in 10 (22%) of 46 patients with rituximab-refractory disease, indicating the potential of alternatively targeting CD19 to improve outcome in such patients,” the researchers noted.
Observed adverse events included infusion-related reactions in 12% of patients, and 1 patient with a grade 4 reaction. Neutropenia occurred in 12% of patients, including 8 patients with grade 3/4 neutropenia. No treatment-related deaths occurred.
“The tolerability of MOR208 provides a rationale for combination studies, especially in elderly patients or those unsuitable for high-dose chemotherapy and stem-cell transplantation,” the researchers wrote.
