Richardson Discusses the Evolving Multiple Myeloma Treatment Landscape

Paul Richardson, MD, director of clinical research at the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute in Boston, Massachusetts, RJ Corman professor of medicine at Harvard Medical School, delves into some of the studies significantly impacting the multiple myeloma treatment landscape and outcomes for patients.

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0:09 | Hello, everyone. My name is Dr. Paul Richardson. I serve as the director of Clinical Research at the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute in Boston, Massachusetts. I am also the RJ Coleman professor of medicine at Harvard Medical School. It was my privilege to be part of a panel on a friday symposium that this year is ASH in San Diego… which was particularly educational for all those who attended. My particular remit for the symposium was to discuss the treatment landscape in newly diagnosed myeloma and how this is evolving. I really wanted to start by just emphasizing what we showed, which was that this has evolved very rapidly over the last 2 decades, from doublets to triplets, further differentiation between transplant eligible and transplant ineligible patients recognizing, however, that the basic ingredients look the same. And in that context, the impact of CD38 antibodies has been quite remarkable. This is just an adaptation of the NCCN guidelines, but it gives you an idea of the breadth and scope of the regimens that are available to us.

1:17 | What I shared with the audience was just to emphasize the importance of CD38 targeting and how this is so important in myeloma pathobiology, and the implications of this are substantial in the upfront space. Data at ASH really served to nail this down. I wanted to emphasize the mechanism of action of CD38 targeting. Basically, CD38 monoclonal antibodies are active against myeloma via multiple mechanisms. This minimal load immunomodulatory activity is important, but so too, the toxic activity complement dependent cytotoxicity, antibody dependent cell mediated cytotoxicity, and also, antibody dependent cellular phagocytosis. And this particular piece is important to bear in mind, because this complexity of effects in the immune system has a radical impact in terms of disease pathobiology. We have seen this validated in multiple settings. Importantly, we see a shift away from the immunosuppressive tumor microenvironment and better antitumor immune responses. So combination strategies are very exciting.

2:24 | To give you examples that support this notion, obviously the MAIA trial [NCT02252172] has been a landmark study in the elderly and frail with dramatic results seen. In the same context, PERSEUS [NCT03710603] was presented as a late breaking abstract by Pieter Sonneveld, MD, PhD. This was in the transplant-eligible population, and here, Pieter displayed really remarkable results with the benefit of combining daratumumab [Darzalex] to [bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd)]. This built very nicely on the excellent results from GRIFFIN [NCT02874742], which supported this particular trial in this context, and the data was summarized as follows that basically, the [progression-free survival (PFS)] primary end point was enhanced with a hazard ratio of .42 in favor of the quadruplets. The overall response rates were dramatically in favor of the quadruplet vs the triplet, and the [adverse] effect profile was manageable.