Nelfinavir is an anti-HIV medication that is a protease inhibitor, so it also works by blocking the degradation of proteins. It’s not clear what protein it is targeting in human cells that are not infected with HIV virus, but it seems to really add something. Activity was seen in preclinical models, and it was demonstrated in a phase II trial where a group of patients who were refractory to proteasome inhibitors were treated with bortezomib and nelfinavir; they are showing some very impressive responses.
If approved, how would a CAR T-cell therapy fit into the current treatment landscape?
We are still learning a lot about what CAR T-cell therapy is going to look like. On the one hand, we have seen some incredibly impressive responses that have lasted for a long time but, at the same time, too many of our patients have not responded in the initial trials. Or, they have a good response and relapse afterward. If we manage to make the therapy even better so that it [has curative potential], we will be using it a lot earlier on in therapy. It will be challenging if the toxicity profile remains somewhat difficult to navigate.
Where do the standard backbones of lenalidomide (Revlimid) and dexamethasone or bortezomib and dexamethasone fall with these new agents?
Daratumumab has been looked at in both combinations of these backbones. It has shown clear efficacy in both combinations, and is being used now as second- or third-line therapy routinely. The other new agents have only started to be examined in combinations. There is an ongoing phase III trial that just started combining selinexor with bortezomib and dexamethasone compared with bortezomib and dexamethasone alone. The other new agents are perhaps being used in combinations, but only in very early-phase trials.
Looking to the future of myeloma treatment, what steps should community oncologists start taking?
There are a lot of standard-of-care options right now. At the same time, it appears to be an incurable malignancy, and we know that all of our patients are eventually going to run out of those options. Looking ahead, as these patients are going through their final stages of the current standard-of-care therapy, think about referral to a tertiary care facility that is doing clinical trials. [These researchers] can think about some of these options and combinations that a community oncologist may not have thought of, and these can be very beneficial to patients.