San Diego, California—Preliminary results from an ongoing clinical trial presented at the 2018 ASH Annual Meeting suggest that elderly patients with splenic marginal zone lymphoma (MZL) respond more favorably to ofatumumab than to rituximab.

Although findings from previous single-center studies show that rituximab, the most widely available anti-CD20 monoclonal antibody (MoAb), can control splenic MZL long-term without the need for combination chemotherapy, lead investigator Lydia Scarfo, MD, Università Vita-Salute San Raffaele, Milan, Italy, and colleagues point out the proven significant efficacy of ofatumumab in other types of relapsed or refractory indolent lymphoma.

“Ofatumumab is a fully humanised anti-CD20 MoAb and displays a favorable safety profile with lower incidence and milder infusion-related reactions (IRRs) when compared to rituximab,” explained Dr Scarfo and colleagues.

Based on these data, they conducted a multi-center, phase 2 clinical trial assessing the safety and activity of ofatumumab monotherapy in patients with relapsed or refractory splenic MZL—even after previously treatment with rituximab. Dr Scarfo presented data from an interim analysis of the trial at ASH 2018.

Patients with relapsed or refractory splenic MZL were eligible for inclusion in the trial if they had progressive disease that needed therapy because of splenomegaly, bulky lymph nodes, and/or cytopenias. It was not uncommon for patients to have received previous treatment with anti-CD20 MoAbs.

As of July 2018, Dr Scarfo and colleagues had enrolled 20 patients in the study at 5 cancer centers in Italy (median age, 73.5 years. There were 10 women and 10 men. Of these patients, 16 had previously been treated with rituximab, usually in combination with chemotherapy; 3 patients had rituximab-refractory disease and 2 had undergone splenectomies.

Patients received ofatumumab every week for 8 weeks; the initial dose on day 1 was 300 mg, but for the remaining 7 weeks patients received 1000 mg. The primary end point of the study was the complete remission (CR) rate.

A total of 18 patients experienced at least 1 adverse event, the most frequent of which were neutropenia, thrombocytopenia, IRRs, skin rash/urticaria, and fatigue. Three patients had serious adverse events, including hypersensitivity reactions, pleural effusion, and chest pain (which occurred during infusion). None of the patients experienced dose delays or reductions, and only 1 patient discontinued treatment after 2 doses of the study drug because of IRRs.

For the interim analysis, Dr Scarfo deemed 17 patients as evaluable. These patients had an overall response rate (ORR) of 94%, with 9 (53%) CRs and 7 (41%) partial responses. Of note, the 3 patients with splenic MZL refractory to rituximab achieved responses (2 CR, 1 partial response).

After a median follow-up of 20 months, 15 patients had disease that was still progression-free. Two patients died from disease progression, including the only nonresponsive case and the patient who withdrew from the study after 2 doses because of IRRs. At 1 year, the progression-free and overall survival rates were 86.7% and 100%, respectively.

“Ofatumumab was active and safe in these elderly chemoimmunotherapy-treated patients,” Dr Scarfo and colleagues said. According to them, the IRRs that did occur were often mild and easily manageable, even among patients very high in age and with relevant comorbidity burden. In addition, patient responses to the drug were notably positive.

“The ORR and the CR rate compare favorably with data reported in the literature with rituximab monotherapy also considering that >75% of patients have been previously exposed to rituximab,” Dr Scarfo and colleagues concluded.

“Ofatumumab deserves to be further investigated to better understand its potential role in this setting,” they added.—Hina Khaliq

Scarfo L, Ferrari S, Frustaci AM, et al. Ofatumumab is active and safe in patients with relapsed/refractory splenic marginal zone lymphoma (SMZL): results from the interim analysis of an Italian multicenter phase 2 study (MORE trial). Presented at: the 60th ASH Annual Meeting and Exposition; December 1-4, 2018; San Diego, CA. Abstract 4162.