Systemic interleukin-2 and adoptive transfer of lymphokine-activated killer cells improves antibody-dependent cellular cytotoxicity in patients with relapsed B-cell lymphoma treated with rituximab.

in Clinical cancer research : an official journal of the American Association for Cancer Research by Jesús G Berdeja, Allan Hess, David M Lucas, Paul O'Donnell, Richard F Ambinder, Louis F Diehl, Denise Carter-Brookins, Susan Newton, Ian W Flinn

TLDR

  • The study tested whether adding lymphokine-activated killer (LAK) cells to monoclonal antibodies (rituximab) could improve the effectiveness of treatment for patients with rituximab-refractory CD20+ lymphoma. The study involved 10 patients who received leukapheresis to obtain LAK cells, followed by infusion of rituximab and LAK cells. The results showed that the addition of LAK cells improved the ability of the patient's immune system to kill cancer cells, compared to treatment with rituximab alone. The study was well tolerated, with the most common side effects being fever and fatigue. Two patients achieved a partial remission and five had stable disease. The study's findings suggest that adding LAK cells to rituximab could be a useful treatment option for patients with rituximab-refractory lymphoma.

Abstract

Murine models have shown that antibody-dependent cellular cytotoxicity (ADCC) can be improved with addition of lymphokine-activated killer (LAK) cells to monoclonal antibodies. A pilot trial of rituximab and LAK cells in patients with rituximab-refractory CD20+ lymphoma was conducted to evaluate this approach. Ten patients received 3 million units/m2 of interleukin-2 (IL-2) i.v. qd on days 1 to 5 and leukapheresed on days 8, 9, and 10. The leukapheresis product was cultured with IL-2 for 48 h to produce LAK cells. Patients then received 375 mg/m2 i.v. rituximab and LAK cells on days 10, 11, and 12. The patients also received 3 million units/m2 of IL-2 i.v. for 5 days starting day 10. For safety purposes, the first three patients did not receive any LAK cell infusions. The LAK cell infusions improved the ADCC activity of peripheral blood lymphocytes compared with pretreatment activity and prevented the decline in ADCC seen after infusion of rituximab alone. Therapy was well tolerated and the most clinically significant toxicities were fever and fatigue. Two patients achieved a partial remission and five had stable disease. The results from these studies suggest that the addition of LAK cells to rituximab augments ADCC in patients with rituximab-refractory lymphoma.

Overview

  • The study aims to evaluate the addition of lymphokine-activated killer (LAK) cells to monoclonal antibodies (rituximab) in patients with rituximab-refractory CD20+ lymphoma. The study uses a pilot trial design and involves 10 patients. The methodology includes leukapheresis to obtain LAK cells, followed by infusion of rituximab and LAK cells. The primary objective is to evaluate the safety and efficacy of this approach in improving antibody-dependent cellular cytotoxicity (ADCC) in patients with rituximab-refractory lymphoma. The study is conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board.

Comparative Analysis & Findings

  • The study compares the outcomes observed under two experimental conditions: rituximab alone and rituximab with LAK cells. The results show that the addition of LAK cells to rituximab improved the ADCC activity of peripheral blood lymphocytes compared with pretreatment activity and prevented the decline in ADCC seen after infusion of rituximab alone. The study also found that therapy was well tolerated, with the most clinically significant toxicities being fever and fatigue. Two patients achieved a partial remission and five had stable disease.

Implications and Future Directions

  • The study's findings suggest that the addition of LAK cells to rituximab augments ADCC in patients with rituximab-refractory lymphoma. The study's pilot trial design and small sample size limit the generalizability of the findings. Future studies should evaluate the efficacy and safety of this approach in a larger patient population. Additionally, further research is needed to determine the optimal dosing and timing of LAK cell infusions to maximize the therapeutic benefit. The study's findings may have implications for the treatment of other CD20+ lymphomas and other malignancies that are susceptible to ADCC.
Read Full Article