The second-generation chimeric antigen receptor (CAR) T-cell therapy, bb2121, engineered to target B-cell maturation antigen, a protein on the surface of certain myeloma cells, displayed continuing efficacy and safety in an update of a phase 1 clinical trial in patients with relapsed or refractory multiple myeloma.
“The wide range of potential immune-related adverse events requires multidisciplinary, collaborative management by providers across the clinical spectrum,” according to Michael A. Postow, MD, and colleagues.
The combination cohort consisted of 119 patients who received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for 4 doses followed by nivolumab 3 mg/kg every 2 weeks. The median follow-up was 13.4 months.
“We find that T-cells with highly activated glycolysis pathways ended up performing worse when we tried to make them into CAR T-Cells. Substituting and supplementing heavily with fatty acids did seem to improve this a little,” said David M. Barrett, MD, PhD, at the 2018 American Association for Cancer Research annual meeting.
“The main rationale from the cytotoxic era is to increase efficacy by combining agents that have different mechanisms and nonoverlapping toxicities. The question is whether we can replace nonspecific cytotoxic agents with a specific, more effective immunotherapeutic,” said Donna Przepiorka, MD, PhD, at ASH 2017.
Adding the investigational drug indoximod, an indoleamine 2,3-dioxygenase (IDO) pathway inhibitor, to the checkpoint inhibitor pembrolizumab led to higher response rates in patients with advanced melanoma than what is reported with pembrolizumab monotherapy,
Despite remarkable advancements in the treatment of cancer through the use of targeted agents and immunotherapy, outcomes are still varied, and, for some patients, these regimens provide only a short-term answer.