Ofatumumab and Complement Replacement in Relapsed/Refractory Chronic Lymphocytic Leukemia

Joseph Tuscano, Christina Poh, Aaron Rosenberg, Brian Jonas, Mehrdad Abedi, Gustavo Barisone, Emily Schwab, Kathleen Lundeberg, Paul Kaesberg

Abstract


Background: While many humanized monoclonal antibodies utilize complement-dependent cytotoxicity, the complement depleting effects of these antibodies and the impact of complement replacement on treatment response are not well-described.

Methods: We conducted a phase 2 trial involving patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Patients were treated with ofatumumab with fresh frozen plasma (FFP) used as a source of complement replacement. The primary endpoint was objective response rate. Correlative endpoints included complement levels (C3 and C4) and complement activity (CH50) which was drawn at baseline and after ofatumumab with FFP administration.

Results: Among 12 enrolled patients, overall response rate was 83% with two patients (17%) achieving a complete response. While only two (17%) patients had low complement activity at baseline, eight (67%) developed low levels of complement activity after ofatumumab treatment with FFP replacement. The magnitude of complement depletion did not correlate with response. Adverse events were minimal. The combination of ofatumumab and FFP demonstrated tolerability and surprising activity in high-risk CLL patients.

Conclusions: The combination of ofatumumab and FFP demonstrated tolerability and surprising activity in high-risk CLL patients. Complement replacement should be studied further as a minimally toxic approach to improve efficacy of monoclonal antibody-based regimens.




J Hematol. 2020;9(3):79-83
doi: https://doi.org/10.14740/jh721

Keywords


Chronic lymphocytic leukemia; Ofatumumab; Fresh frozen plasma

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Journal of Hematology, bimonthly, ISSN 1927-1212 (print), 1927-1220 (online), published by Elmer Press Inc.                            
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