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Creating Lasting Benefit With CAR T-Cell Therapy in Myeloma

Caroline Seymour
Published: Monday, Mar 11, 2019

Noopur Raje, MD
Noopur Raje, MD
Triplet and quadruplet regimens comprised of immunomodulatory agents, proteasome inhibitors, and monoclonal antibodies are increasing the odds of transforming multiple myeloma into what has traditionally been thought of as a chronic disease to a curative disease, explained Noopur Raje, MD, adding that cellular therapy is bound to increase these chances.

, Raje, professor of medicine at Harvard Medical School and director of the Center for Multiple Myeloma at Massachusetts General Hospital Cancer Center, discussed the current treatment landscape of multiple myeloma, with a specific focus on available triplet regimens and the recent data with CAR T-cell therapy.

OncLive: What does the current treatment landscape for multiple myeloma look like?

Raje: We have lots of FDA-approved drugs and different combinations. In the upfront setting, the majority of us will use a triplet regimen followed by transplant in the transplant-eligible population as well as maintenance. There is a move towards giving 4-drug regimens upfront, with the goal of getting to and maintaining a minimal residual disease (MRD)-negative state. By doing that, we hope to transform what we're seeing as a chronic disease in some patients into a fraction of cured patients.

In the United States, the majority of our patients are progressing after having been on a lenalidomide (Revlimid) maintenance approach. We are mostly picking a pomalidomide (Pomalyst)-based approach, whether it's with daratumumab (Darzalex), carfilzomib (Kyprolis), or some other agent.

Could you discuss the data with these triplet regimens?

We have good data with carfilzomib, pomalidomide, and dexamethasone (KPd). This regimen has been used in the relapsed/refractory setting with about a 60% to 70% response rate. Additionally, the duration of response can be close to 8 or 9 months. The regimens with daratumumab have been very impressive. We see response rates of 60% with daratumumab, pomalidomide, and dexamethasone and a duration of response close to 8 to 10 months. That’s pretty remarkable in the relapsed/refractory setting.

How do these responses differ from those achieved with CAR T-cell therapy?

With CAR T-cell therapy, we've seen response rates greater than 90%. However, this is a very different patient population. We're not talking about first relapse. On average, these patients have had 7 prior lines of therapy. Besides CAR T-cell therapy, these patients would not have anything else. These hospice-like patients who are quad- and penta-refractory have seen both immunomodulatory agents [lenalidomide and pomalidomide], both proteasome inhibitors [carfilzomib and bortezomib (Velcade)], and have also seen the monoclonal antibody daratumumab.


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Community Practice Connections™: 22nd Annual International Congress on Hematologic Malignancies®: Focus on Leukemias, Lymphomas and MyelomaMay 30, 20192.0
Online Medical Crossfire®: 5th Annual Miami Lung Cancer ConferenceMay 30, 20196.5
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