Exceptional Response to Fixed Duration Obinutuzumab and Venetoclax in a Patient with Chronic Lymphocytic Leukemia: A...

Obinutuzumab is a standard treatment for chronic lymphocytic leukemia (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 obinutuzumab in the ramp-up phase followed by limited venetoclax.

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 10 years, developed bulky disease, and treatment was initiated following CLL-14. On cycle 1 day 1 (C1D1), she was treated with 100 mg of obinutuzumab; she received 900 mg 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 400 mg daily. Further treatment was limited by cytopenias. Bone marrow biopsy within 4 months of treatment with a total of 1,000 mg of obinutuzumab and ∼13,000 mg 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, and subsequent peripheral blood flow cytometry analysis revealed no evidence of CLL. The patient remains in complete remission 34 months following obinutuzumab therapy.

The degree of pancytopenia and the exceptional clinical response to minimal dose of obinutuzumab by this patient suggests an unusual sensitivity to obinutuzumab.