Safety Profile of Maintenance Obinutuzumab in Patients with Primary CNS Lymphoma in Complete Response
Authors: Doolittle Nancy D. , Ambady Prakash , Peereboom David M. , Ney Douglas E. , Junck Larry , Umemura Yoshie , Strowd III Roy Ervin , Lesser Glenn J. , Schiff David , Fadul Camilo E. , Glantz Michael , Dunbar Erin M. , Barth Peter , Pan Edward , Thomas Alissa A. , Fu Rongwei , Neuwelt Edward A. 
Published: November 2020

Background: Although high initial response rates have been reported, fewer than 50% of newly diagnosed primary CNS lymphoma (PCNSL) patients remain disease free 2 yrs after high-dose (HD) methotrexate (MTX)-based regimens. Treatment options at relapse including HD chemotherapy with or without autologous stem cell transplantation and/or whole brain radiotherapy can lead to considerable toxicity and are not ideal especially for elderly and high-risk patients. New approaches to prolong disease control and response duration in PCNSL are needed. Maintenance rituximab has increased response duration in follicular and mantle cell lymphomas. Several reports (Ney and Abrey [2009]; Ambady et al [2020]) suggest that maintenance rituximab after achieving complete response (CR) to MTX-based chemotherapy, will prolong disease control in PCNSL. We designed a randomized study to evaluate the effect of maintenance obinutuzumab on CR duration in CD20+ B-cell PCNSL patients who attain CR to first-line HD MTX-based chemotherapy. We report adverse events (AEs) to-date in the maintenance group.
Methods:This was a multicenter, non-blinded, randomized phase II study, with an estimated sample size of 120 patients randomly assigned to maintenance obinutuzumab or observation. Patients in the maintenance group received obinutuzumab (1000 mg) every 60 days for 2 yrs. Eligible patients were within 75 days of completing first-line MTX-based regimen, and in CR. The primary endpoint was CR duration. Lab tests and safety assessments were performed throughout the study until 60 days after the patient's last obinutuzumab infusion. We graded AEs according to NCI CTCAE v4, and summarized AEs descriptively. Clinical Trial Information: NCT02498951.
Results: As of July 1, 2020, 24 patients were enrolled at 11 U.S. centers. Twelve patients (5F, 7M) with median age of 68 yrs (range: 39 - 82), median KPS 90 (range: 80 - 100) were in the maintenance group. Seven of the 12 patients were older than 65 yrs. The 12 patients received 87 obinutuzumab infusions (median 7 [range 2 - 12]). The only grade (Gr) 3 AEs attributable to study drug were nausea, vomiting and skin infection (1 patient [8%] each). The most frequent Gr 2 AEs were respiratory infection and diarrhea (2 patients [17%] each). Gr 2 nausea, vomiting and skin infection occurred in 1 patient (8%, each). Gr 1 dizziness and flushing during cycle 1 infusion occurred in 3 patients (25%).
Conclusions: Maintenance obinutuzumab was well tolerated with an encouraging safety profile in PCNSL patients in remission. However, enrollment closed prematurely due to slow accrual made worse by the coronavirus pandemic. Thus the role of maintenance obinutuzumab in prolonging CR duration in this patient population remains unknown.

Disclosures
Barth: Sanofi:Membership on an entity's Board of Directors or advisory committees.