Dr. Usmani on PD-1/PD-L1 Inhibitors in Hematologic Malignancies

Saad Z. Usmani, MD, clinical professor of medicine, UNC-Chapel Hill School of Medicine, chief, Plasma Cell Disorders Program, director, clinical research in hematologic malignancies, Levine Cancer Institute, discusses the evolution of PD-1/PD-L1 inhibitors in the treatment of patients with hematologic malignancies.

In terms of the PD-1/PD-L1 pathway, physicians have seen efficacy in Hodgkin lymphoma. Initial clinical observations of nivolumab (Opdivo) were published about 3 years ago in the New England Journal of Medicine. Since then, several clinical trials have explored checkpoint inhibitors in frontline strategies, early relapse, as well as post-transplantation. It looks like there is good activity using both PD-1/PD-L1 inhibitors in each of those strategies, Usmani says.

Pembrolizumab (Keytruda) is the only immunotherapy agent physicians have data for in myeloma. It has been studied in combination with lenalidomide (Revlimid) and dexamethasone as well as pomalidomide (Pomalyst) and dexamethasone. These data came from small single-center phase I/II trials. Phase III trials were halted by the FDA in 2017. Following that, checkpoint inhibition was deemed unsafe in combination with immunomodulatory drugs, says Usmani. However, newer clinical trials exploring checkpoint inhibition with other drug classes are ongoing. Exploration of other checkpoint inhibitors including CTLA-4 and OX40 are making their way into early phase clinical trials as well, states Usmani.