Paul G. Richardson, MD

Question

How is the treatment of multiple myeloma changing, particularly as newer agents receive approval or expanded indications (eg, daratumumab granted Priority Review for the first line, denosumab approved to prevent skeletal-related events [SREs])?

Answer

There are multiple new advances that are allowing us to tailor therapy more and more for each patient — that in and of itself is encouraging. This allows us to exploit novel combinations in a way that we’ve never been able to do before, and so adapt treatment to each individual patient, thus giving the best chance of optimizing outcome, both in the short and long term.

Question

How has maintenance therapy changed, and what is its role now for patients with multiple myeloma?

Answer

The overwhelming body of evidence now supports continuous therapy and maintenance until progression, which is a new standard subsequent to FDA [US Food and Drug Administration] approval last year, both in the initial treatment phase and after relapse. Maintenance has become a cornerstone of management in myeloma and is thus recommended typically until progression and/or toxicity.

The data support continuous maintenance, with lenalidomide as the gold standard and so-called backbone, with additional agents added to it, rationally tailored to each patient. For example, you might add a proteasome inhibitor to lenalidomide for higher-risk patients, and you also might consider adding an antibody such as elotuzumab. In my opinion, if it is not possible to give maintenance therapy, it should be for definite reasons such as patient tolerability, specific safety concerns, and/or personal choice.

Question

Where are we now with CAR-T therapy for multiple myeloma? What can be expected in the near future, in terms of incorporating it into practice?

Answer

CAR-T cell therapy is very exciting but it is experimental and remains subject to protocol-directed use at this stage in its development as a treatment option in myeloma. It is not yet approved, so it has to be utilized strictly under research conditions and as part of carefully designed clinical trials.

The initial information around its application has been very promising, but it remains early with some significant concerns around safety as well as durability of response in studies to date.

Question

Do you think immune checkpoint inhibition will have a place in the treatment landscape for multiple myeloma, given the increased risk of death in clinical trials? Is the mechanism for the increased risk of death known?

Answer

Yes, I do, despite some recent setbacks. Specifically, there was disappointment in 2 large phase 3 studies with excess toxicities seen using pembrolizumab. There were a variety of issues that contributed to the toxicities that were encountered, and in my view a better understanding of them will allow these issues to be better managed.

The basic principles of checkpoint inhibition and immune modulation would seem ones that should be continued to be studied, especially given the promise of the original phase 2 data with pembrolizumab, as well as the early success seen with other agents such as nivolumab used in combination in this setting.

Question

What new approaches are you excited about for the treatment of multiple myeloma in the future?

Answer

Immunotherapy, and all that that entails, such as targeting BCMA, as well as better understanding on how to continue to improve outcomes with CD38 modulation and other approaches such as vaccines, are all very exciting. The continued development of immunomodulatory drugs, proteasome inhibitors, and other novel drugs with unique mechanisms of action are equally important new directions to emphasize.