Management of Relapse/Refractory Multiple Myeloma

Sagar Lonial, MD, FACP:I’m Dr Sagar Lonial, chair and professor of the Department of Hematology and Medical Oncology at the Winship Cancer Institute of Emory University in Atlanta, Georgia.

Management of patients in the context of relapsed and refractory myeloma, who for the sake of this discussion we’ll think about as patients who have seen at least three or more prior lines of therapy, is somewhat limited at this time point.

We will often go to chemotherapy-based combinations, whether they are aggressive, in-patient approaches such as DCEP [dexamethasone, cyclophosphamide, etoposide, and cisplatin] or VDT PACE [bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide], or outpatient combinations using low-dose oral cyclophosphamide in combination with agents that the patient has often seen. These can often include things like proteasome inhibitors, antibodies, or immunomodulatory agents.

Of late, we have had the availability of a medicine called Selinexor, which is approved in combination with dexamethasone for patients with refractory myeloma. What we do know is that many of these treatment approaches in heavily pretreated patients result in significant adverse events, adverse effects, and toxicity, and the benefit in terms of duration of remission is often quite limited.

I think when we talk about unmet needs for the patients, particularly in relapsed and refractory myeloma, it’s the ability to control disease without giving patients too many adverse effects. The FDA risk benefit ratio that often comes up in the context of 3, 4, or 5 prior lines of therapy. The goal is being able to get durable disease control, or even stability of disease in some situations, with a treatment approach that is easy and relatively well tolerated, and doesn’t necessarily compromise performance status, or overall quality of life.

BCMA, or B-cell maturation antigen, is a cell surface protein that is somewhat like every other cell surface protein such as CD38 [cluster of differentiation 38], or CD56 [neural cell adhesion molecule], or CD45 [lymphocyte common antigen]. What is unique about BCMA is that it is far more limited with plasma cells, both normal and malignant plasma cells. Ligating BCMA, with many of its natural ligands, actually results in things like drug resistance and proliferation and drug resistance in a number of different key targets.

What I think is really interesting about BCMA is that it wasn’t until recently that we started to identify that BCMA was potentially a really good target for patients with myeloma. Unlike CD38 or other proteins like SLAMF7 [signaling lymphocytic activation molecule F7] , it is almost exclusively expressed on plasma cells and is expressed at the time of diagnosis all the way through relapse and subsequent refractory relapse as well. It does represent an exciting and important limited target in myeloma.

Transcript edited for clarity.