Treating Transplant-Ineligible Multiple Myeloma

Saad Z. Usmani, MD, FACP:The patients who are transplant ineligible make up more than half of the myeloma patients who we see in the world. A lot of research has focused on developing newer strategies and incorporating newer treatment mechanisms of action for the transplant-eligible patients, but not as much for the transplant-ineligible patients. The goals of care for most of those patients are long-term disease control. And so the areas of unmet need have been: How do we incorporate some of the novel therapies and the new treatment paradigms for those patients?

Generally, the treatment approach for transplant-ineligible patients had been to utilize 2-drug combinations until more recently. In the past 3 years, we’ve generated data showing that the 3-drug combinations work better for those patients in terms of providing a better depth of response and better progression-free survival. The SWOG [Southwest Oncology Group]-[SO777] data tell us that even the overall survival is better when you’re combining 3 drugs for these patients. There has been a little shift in how we are starting to approach treatment for these patients.

The past 4 years have seen the incorporation of 2 monoclonal antibodies, elotuzumab and daratumumab, into the armamentarium of myeloma therapy. Elotuzumab targets SLAMF7 [signaling lymphocytic activation molecule F7] and daratumumab targets CD38 on the surface of myeloma cells. For the most part, both these monoclonal antibodies are utilized in combination with other available myeloma therapies for patients who’ve had at least 1 relapsed status. These are patients who have received frontline treatment, and now the disease is coming back. The case for daratumumab changed about a year ago. It got its first approval in the newly diagnosed setting—combined with VMP—which stands for bortezomib, melphalan, and prednisone. This was based on a large randomized phase III trial that was done primarily in Europe.

Elotuzumab is currently approved in combination with lenalidomide and dexamethasone for patients who’ve had at least 1 prior line of treatment. Daratumumab is approved, not just for the frontline setting but also combined with lenalidomide-dexamethasone, bortezomib-dexamethasone, and pomalidomide-dexamethasone in the relapsed-refractory space.

Transcript edited for clarity.