Dr. Brody on Addressing Acquired Resistance to Immunotherapy in Non-Hodgkin Lymphoma

Joshua Brody, MD, director, Lymphoma program, Icahn School of Medicine, Mount Sinai Hospital, discusses addressing required resistance to immunotherapy in non-Hodgkin lymphoma.

Despite the promising data seen with in-situ vaccines in the field, it is common knowledge that patients’ tumors can become resistant to vaccines or any type of immunotherapy through antigen escape, explains Brody. With regard to CAR T-cell therapy, this can mean the loss of CD19 from the tumor. With bispecific antibodies against CD20, this can mean CD20 loss, adds Brody. With every other type of immunotherapy where T cells recognize tumors through their major histocompatibility (MHC) class 1 expression, it can be MHC class 1 loss. This has been well described for many types of cancer after a patient receives a PD-1 inhibitor. In fact, class 1 loss is one of the most common types of resistance to checkpoint inhibitors, notes Brody.

Investigators started to observe this in some of the patients with advanced-stage indolent non-Hodgkin lymphoma who had been treated with an in-situ vaccine. Brody and colleagues shared some data that have been developed in the lab in their attempt to address antigen escape. They found that there are many ways to solve the problem of antigen escape in CAR T-cells. After giving an anti-CD19 CAR T-cell, an anti-CD22 CAR T-cell can be given as treatment, in case the patient lost the CD19 antigen, concludes Brody.