Phase II Trial of Obinutuzumab and Ice Chemotherapy in Relapsed Mature B-Cell Non-Hodgkin Lymphoma

Author Type(s)

Faculty, Resident/Fellow

Document Type

Abstract

Publication Date

2022

DOI

10.1002/pbc.29735

Journal Title

Pediatric Blood and Cancer

Department

Pediatrics

Second Department

Medicine

Third Department

Public Health

Abstract

Background: Relapsed/refractory B-cell non-Hodgkin lymphoma (BNHL) (diffuse large B-cell lymphoma [DLBCL] and Burkitt's lymphoma [BL]) is associated with a high degree of chemotherapy resistance leading to dismal outcomes. Obinutuzumab, a humanized, glycoengineered monoclonal CD20 antibody, exhibited enhanced ADCC and apoptosis compared to rituximab in pre-clinical testing against rituximab resistant BL and is approved for initial treatment and relapsed/refractory disease after rituximab containing therapy in follicular lymphoma and newly diagnosed patients with CLL. Objectives: To investigate the safety and activity of obinutuzumab (O) in combination with ifosfamide, carboplatin, and etoposide (ICE) in children, adolescents and young adults with relapsed/refractory mature B-NHL. Design/Method: Patients ages 3-31 years with relapsed or refractory CD20+ B-NHL were eligible. All patients received a window of 4 doses of obinutuzumab on days -14, -10, -6 and -2 prior to starting immunochemotherapy. Progression during the window phase allowed proceeding directly to O-ICE cycle 1. Patients received two 3-week cycles of O-ICE with 2 weekly doses of obinutuzumab each cycle. Patients received CNS directed IT therapy along with dexamethasone. Patients with a partial response (PR) or complete response (CR) after cycle one were allowed to proceed to hematopoietic stem cell transplant (HSCT). Patients without progressive disease (PD) proceeded to cycle 2. A third cycle of therapy was allowed as needed. Response assessments were as per the International Pediatric NHL Response Criteria (IPNHLRC). Study was registered as NCT02393157. Results: Six patients with Burkitt Lymphoma, ages 7-20 years have enrolled to date. Patients included 1 CNS+, 1 in second relapse, and 1 with progression to Burkitt leukemia. Following a median of 2 cycles (range 1-3), there were 4 PRs, 1 CR, and 1 MR (ORR 83.3%). Five patients proceeded to HSCT. The mixed response patient later suffered from progressive disease and died prior to eligibility for HSCT. Three with PR died from disease complications following HSCT. One patient with PR and one with CR are alive following HSCT and remain disease free at 4 and 5 years post therapy. No O-ICE associated adverse events have been observed. Conclusion: In this phase 2 study, the addition of obinutuzumab to standard salvage chemotherapy has been well tolerated in 6 patients, with the absence of grade 3 or higher adverse events, and 5 patients successfully proceeding to HSCT. Recruitment is ongoing.

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