CAR-natural killer cell therapy induces response in non-Hodgkin lymphoma, CLL
Natural killer cells transduced with chimeric antigen receptors induced high response rates among patients with relapsed or refractory CD19-positive non-Hodgkin lymphoma and chronic lymphocytic leukemia, according to results of a phase 1/phase 2 study published in The New England Journal of Medicine.
The anti-CD19 CAR-natural killer (NK) cell therapy also appeared safe.
“There is no clear standard of care once a patient with a CD19-positive tumor has relapsed multiple times ... [and] the outcome for these patients is dismal,” Katy Rezvani, MD, PhD, director of translational research in the department of stem cell transplantation and researcher in the division of internal medicine at The University of Texas MD Anderson Cancer Center, told Healio. “For the majority of patients enrolled in our study, a clear alternative standard of care did not exist. An allogeneic hematopoietic stem cell transplant may be considered for these patients, but only a minority will be eligible due to lack of a donor or the prohibitive toxicities related to the procedure.”
Previous studies showed CAR T-cell therapy directed against CD19 generates remission rates of 68% to 93% among patients with acute B-cell lymphoblastic leukemia, 57% to 71% among patients with CLL, and 64% to 86% among patients with non-Hodgkin lymphoma.
Rezvani and colleagues administered HLA-mismatched anti-CD19 CAR-NK cells derived from cord blood to 11 patients (median age, 60 years; men, n = 7) with relapsed or refractory non-Hodgkin lymphoma or CLL who received a median four (range, 3-11) previous lines of therapy. The NK cells had a retroviral vector that expressed genes encoding anti-CD19 CAR, interleukin-15, and inducible caspase 9 as a safety switch. Investigators expanded the cells ex vivo and administered them in a single infusion at one of three doses (1 × 105, 1 × 106 or 1 × 107 CAR-NK cells/kg) after lymphodepleting chemotherapy.
Median follow-up was 13.8 months (range 2.8-20).
Results showed objective responses in eight (73%) of the 11 treated patients, seven of whom (four with lymphoma and three with CLL) achieved complete remission. One patient had remission of the Richter transformation component but continued to have persistent CLL.
Responses occurred within 30 days after infusion at all dose levels. The infused CAR-NK cells expanded and persisted for at least 1 year at low levels.
Patients who received the CAR-NK cells did not develop treatment-related cytokine release syndrome, neurotoxicity or graft-versus-host disease. Researchers also did not observe an increase in levels of inflammatory cytokines, including interleukin-6, from baseline.
“We don’t fully understand why [there were no serious adverse events],” Rezvani said. “We believe perhaps this could be related to differences in the inflammatory proteins that T cells and NK cells produce when they encounter their target.”
The maximum tolerated dose was not reached.
“The current trial is designed to enroll 60 patients with follow-up of 1 year [to] measure OS,” Rezvani said. “In addition, we are working with our commercial partner Takeda Pharmaceutical to develop a large multicenter study with the objective of obtaining FDA approval for our product.” – by John DeRosier
For more information:
Katy Rezvani, MD, PhD, can be reached at The University of Texas MD Anderson Cancer Center, Building 318, 1515 Holcombe Blvd., Houston, TX 12345; email: firstname.lastname@example.org.
Disclosures: Rezvani reports institutional research funding from Takeda Oncology. Please see the study for all other authors’ relevant financial disclosures.