SACRAMENTO, CA – What are the complement depleting effects of humanized monoclonal antibodies and the impact of complement replacement on treatment response in patients with hard-to-treat chronic lymphocytic leukemia?

A small phase 2 trial published in the Journal of Hematology involved patients with relapsed/refractory CLL. Researchers from the University of California Davis Comprehensive Cancer Center and the Northern California VA Healthcare System, both in Sacramento, joined with the University of Washington in Seattle in the study.1

The team treated patients with ofatumumab with fresh frozen plasma (FFP) used as a source of complement replacement. Defined as the primary endpoint was objective response rate.

The authors reported that, 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,” researchers explained. “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.”

The authors urged that complement replacement should be studied further as a minimally toxic approach to improve efficacy of monoclonal antibody-based regimens.

“Given the small sample size of this study, the complement depleting effects of ofatumumab without FFP replacement would be considered provocative and exploratory,” researchers noted. “In addition, while not examined, longer treatment duration with ofatumumab or other antibodies may produce even greater complement depletion than what is observed in our study. Thus, the potential magnitude of monoclonal antibody-mediated complement depletion cannot be overstated.”

  1. Tuscano J, Poh C, Rosenberg A, et al. Ofatumumab and Complement Replacement in Relapsed/Refractory Chronic Lymphocytic Leukemia. J Hematol. 2020;9(3):79-83. doi:10.14740/jh721