Hearn Jay Cho, MD, PhD
In 2017, the FDA halted trials examining checkpoint inhibitors in multiple myeloma due to excess toxicity, which left an unclear role for this class of agents in this disease.
State of the Science Summit™ on Multiple Myeloma, which was held ahead of the 2018 ASH Annual Meeting, Cho, associate professor of Medicine, Hematology/Oncology, Mount Sinai Hospital, discussed these classes of immunotherapy under investigation in multiple myeloma.
OncLive: What types of immunotherapy are being investigated?
: I covered 3 classes of immunotherapies. The first class is checkpoint inhibitors. These have already been approved for patients with solid tumors and classical Hodgkin lymphoma. The second class are ADCs, which are combinations of tumor-targeting antibodies with chemotherapy agents. The third are bispecific engineered agents. These are derivatives of antibodies that bring T cells together with tumor cells, thereby activating the T cells.
Trials with checkpoint inhibitors were halted due to safety data. Will they undergo further investigation?
In the interim analysis of the studies with pembrolizumab (Keytruda), it was noted that there were higher numbers of deaths in the experimental arm than in the control arm. The experimental arm consisted of a combination of pembrolizumab and pomalidomide (Pomalyst) or lenalidomide (Revlimid) and dexamethasone. The control arm was either pomalidomide and dexamethasone or lenalidomide and dexamethasone. The concern was that these deaths were due to immune-related adverse events, which is a known risk of checkpoint inhibitor therapy. The other concern was that there did not appear to be a survival difference between the experimental arm and the control arm.
Ongoing studies are investigating combination therapy. We're combining things like daratumumab (Darzalex) with immune checkpoint inhibitors. Current clinical trials include nivolumab (Opdivo) and atezolizumab (Tecentriq), which are both FDA approved for certain solid tumor [indications]. It's important that we continue this line of work under appropriate safety review in order to find what the role for these powerful immunotherapy agents will be.
What are some potential targets under development?
There are 2 FDA-approved monoclonal antibodies for myeloma; one is targeting CD38, which is daratumumab. The other is targeting SLAMF7, which is elotuzumab (Empliciti). Both of these agents, particularly in combination, show excellent responses and long-term follow-up data. There are a number of antibody-based therapies targeting BCMA, similar to the chimeric antigen receptor (CAR) T-cell therapies. Some of these have shown excellent activity.
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