Sagar Lonial, MD
For patients with multiple myeloma who experience late relapse or are refractory, management of the disease can be challenging; however, a number of new agents are emerging with promising results in this space, explained Sagar Lonial, MD.
At the 23rd Annual International Congress on Hematologic Malignancies: Focus on Leukemias, Lymphomas, and Myeloma®
, Lonial addressed what agents are being investigated now in this space. Early data are showcasing potential with therapies such as targeted agents, antibody-drug conjugates (ADCs), bi-specific T-cell engagers (BiTEs), and chimeric antigen receptor (CAR) T-cell therapies.
“This field is really going to move towards incorporation of more immune-based approaches and really using precision medicine to help define the kinds of patients that might be more sensitive or resistant to certain targeted therapies,” said Lonial.
For example, results of an ongoing phase II study showed that the combination of venetoclax (Venclexta), carfilzomib (Kyprolis), and dexamethasone elicited a 100% objective response rate with a very good partial response or better rate of 86% for patients with multiple myeloma with relapsed/refractory t(11;14) disease.1
Moreover, the XPO1 (CRM1) inhibitor selinexor has demonstrated intriguing response rates and survival benefit in patients with penta-refractory disease.2
However, in February 2019, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 8 to 5 against accelerated approval of a new drug application for selinexor in this patient population, citing significant safety concerns that resulted in patient deaths in the phase IIb STORM trial.3
Additionally, STORM was a single-arm combination trial and a prior phase I study had not demonstrated strong monotherapy activity with the agent.
In an interview with OncLive
during the meeting, Lonial, professor and chair, Department of Hematology and Medical Oncology, Emory University School of Medicine, chief medical officer, Winship Cancer Institute of Emory University, discussed some of the emerging agents for the treatment of patients with late relapse in multiple myeloma.
OncLive: What is the current state of multiple myeloma treatment, specifically for patients who are in late relapse?
: The management of patients with late relapse or refractory myeloma is very challenging. A group [of researchers] put together a series of almost 150 patients who are basically quad- or penta-refractory in the daratumumab (Darzalex) era and showed that their median expected overall survival is about 11 months. Duration of response to any therapy tends to be very short, so this is a group of patients who clearly represent an unmet medical need.
The use of selinexor or other targets that go after XPO1 is certainly something that looks interesting and exciting, and despite the fact that the FDA's ODAC gave it a negative review, it is clearly an active agent in this subset of patients, and how we combine it is a future question.