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CAR T Cells Could Provide Curative Strategies in Myeloma

Brandon Scalea
Published: Monday, Sep 17, 2018

Deepu Madduri, MD

Deepu Madduri, MD

Encouraging clinical trial findings have demonstrated that chimeric antigen receptor (CAR) T-cell therapy has promise for patients with relapsed/refractory multiple myeloma; however, more data are needed to decide the best placement of this therapy, said Deepu Madduri, MD.

“The biggest challenge we have with this therapy is slot limitation,” said Madduri, an assistant professor at Mount Sinai Hospital.

Results from the multicenter phase I CRB-401 study evaluating the anti-BCMA CAR T-cell therapy bb2121 in heavily pretreated patients with relapsed/refractory patients showed positive progression-free survival (PFS) results. The median PFS was 11.8 months and the median duration of response was 10.8 months, according to updated data presented at the 2018 ASCO Annual Meeting.1

Moreover, the objective response rate was 95.5% and the complete response (CR) rate or stringent CR rate was 50%. The agent also appeared to be well tolerated.

A further analysis suggested that early minimal residual disease (MRD) negativity could predict deepening myeloma response in patients treated with bb2121.2

In a landscape currently comprising monoclonal antibodies, proteasome inhibitors, and immunomodulatory (IMiD) agents, CAR T-cell therapy could provide yet another option to the growing armamentarium.

In an interview with OncLive®, Madduri discussed the role of CAR T-cell therapy and other novel treatment options for patients with relapsed/refractory multiple myeloma.

OncLive: Please discuss the current treatment landscape for relapsed/refractory multiple myeloma.

Madduri: Generally, triplet therapies have taken the front seat over dual combination therapies in this setting. We tend to use an IMiD agent, a proteasome inhibitor, and a steroid along with it. Recently, with the introduction of monoclonal antibodies, we are using quadruplet regimens in some cases. We can actually do lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (VRD), plus daratumumab (Darzalex). These are in clinical trials right now.

What are your strategies for elderly or frail relapsed/refractory patients?

For this subset, before the first trial established lenalidomide and dexamethasone (Rd) as frontline treatment for patients ineligible for stem cell transplant, the SWOG S0777 findings established the idea that you could use a triplet therapy. They actually tend to do better with this regimen. This trial tested VRd against Rd. It included patients who were transplant ineligible, which helped. It showed the OS and PFS was better for the triplet than the doublet.

A better strategy, we found out, is using VRD “light,” which uses the same combination but at a lower dose. In this trial, they gave bortezomib once weekly instead of twice weekly, and it was a 35-day cycle instead of the regular 28-day cycle. Patients also received 15 mg of lenalidomide versus 25 mg.

How does the role of CAR T-cell therapy fit into all of this?

This is something we do quite often in our clinic. We have been involved from the very beginning. In terms of CAR T cells, they are showing very promising data. I know the data were recently presented at the 2017 ASH Annual Meeting and the 2018 ASCO Annual Meeting, and these data showed that all populations of patients have over an 11-month PFS. With MRD negativity, PFS was prolonged to 17.7 months.


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