Supplementary Material for: Exceptional Response to Fixed Duration Obinutuzumab and Venetoclax in a Patient with Chronic Lymphocytic Leukemia: a case report

Introduction: Obinutuzumab is a standard treatment for CLL in combination with venetoclax, following the CLL 14 trial. The purpose of the gradual ramp-up dosing is to mitigate toxicity and prevent tumor lysis; while these ramp-up doses are considered active; they are not considered to be definitive therapy. We describe the case of a CLL patient who had an exceptional response to obinatuzumab in the ramp-up phase followed by limited venetoclax. Case Report: A 73-year-old female with CLL, with Trisomy 12 (70.5%), deletion of 13q (14%), and 3 copies of 11, who had been monitored for ten years, developed bulky disease, and treatment was initiated following CLL 14. On cycle 1 day 1 (C1D1) she was treated with 100mg of Obinutuzumab; she received 900mg on C1D2. When she returned for treatment on C1D8 she was found to have profound pancytopenia, and obinutuzumab was held. She received no further obinutuzumab but was started on venetoclax and received 12 weeks of treatment, with maximum dose reached in ramp-up being 400mg daily. Further treatment was limited by cytopenias. Bone marrow biopsy within four months of treatment with total 1,000mg of obinutuzumab and ~13,000mg venetoclax, revealed trilineage hematopoiesis with only trace evidence of CLL at 0.14%. She was then treated with 4 weeks of rituximab for presumed immune thrombocytopenic purpura (ITP), and subsequent peripheral blood flow cytometry analysis revealed no evidence of CLL. The patient remains in complete remission 34 months following obinutuzumab therapy. Conclusion: The degree of pancytopenia and the exceptional clinical response to minimal dose of obinutuzumab by this patient suggests an unusual sensitivity to obinutuzumab.