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CAR T-Cell Therapy an Emerging Explosion in Myeloma Paradigm

Gina Columbus @ginacolumbusonc
Published: Tuesday, Jan 23, 2018

Nina Shah, MD
Nina Shah, MD
Recent dose-escalation findings in chimeric antigen receptor (CAR) T-cell therapy presented at the 2017 ASH Annual Meeting continue to show high potential in heavily pretreated patients with multiple myeloma.

In the study, the BCMA-directed CAR T-cell therapy bb2121 induced complete remissions for 56% of patients with relapsed/refractory multiple myeloma. Additionally, there was a 94% objective response rate, which consisted of a very good partial response or better for 89% of patients. After 40 weeks of follow-up, the median progression-free survival (PFS) had not yet been reached, and the 9-month PFS rate was 71%. Regarding safety, the treatment was generally well tolerated.

“It is a really exciting time in immunotherapy and an exciting time in myeloma,” said Nina Shah, MD. “We're really hoping that clinical trials will help us to understand where to position these drugs and also if we can do it earlier.”

Shah, associate professor of medicine, University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer, discussed immunotherapy and cellular treatments moving fast through the multiple myeloma pipeline, and the hope for CAR T-cell therapy to eventually move up to earlier lines of treatment in an interview during the 2017 OncLive® State of the Science SummitTM on Hematologic Malignancies.

OncLive: You lectured on immunotherapy and novel agents for refractory myeloma. What developments have we been seeing?

Shah: This is a really exciting field because there are multiple areas where there have been a lot of developments. We talked about the major categories of immunotherapy, including antibody therapy, cellular therapy, and some of the novel twists on antibodies, including antibody-drug conjugates, as well as bispecific antibodies. We talked about the updated elotuzumab (Empliciti) data, as well as that of daratumumab (Darzalex). Both of these have held onto their PFS benefit that they showed in the initial studies. That is exciting because a lot of patients are able to get these therapies sooner in their relapse course and for longer.

We also discussed cellular therapies and there are different categories. There are T-cell receptor (TCR) therapies, such as NY-ESO-1, and there are several clinical trials for this, one of which we are going to be participating in at UCSF. In addition, we talked about the exciting data with CAR T cells. This is exciting because it was just updated at the 2017 ASH Annual Meeting, and the response rates were shown to be 94% in those who were evaluable. Nine out of 10 patients had minimal residual disease (MRD) negativity and we're all very excited that patients with a median 7 lines of treatment could actually get to MRD negativity. We’re looking forward to opening several of those types of clinical trials. 

In addition, we talked about how we could improve on CAR T cells. We have known that persistence matters and intercellular signaling probably matters, but how do we get over the resistance of CAR T-cell therapies? There are some novel ways scientists everywhere, including at UCSF, are looking at trying to keep the CAR T activated and keep them persistent. This is so they could potentially turn them on and off so they can be effective but not toxic. 

We talked about antibody-drug treatments. This includes antibody-drug conjugates, where a toxic drug is linked to an antibody so that the antibody delivers it specifically to the myeloma cell. We also discussed bispecific therapies; these are when antibodies are specific to myeloma cells, but they also have another part that is specific to a T cell. It brings the patients’ own T cells together with the antibody against the myeloma cell with hopes of killing the myeloma cell directly and having some T-cell membrane. That is one of the goals of that therapy. 

2017 was an interesting year for checkpoint inhibitors in myeloma. Can you comment on the clinical trial holds?

A lot of us were very disappointed that the pembrolizumab (Keytruda) trials were halted in the initial phase II trials; there were 60% or 70% response rates, which is very hard to do in patients with myeloma. We know that checkpoint inhibitors probably need another drug to work. It is hard to have the single-agent activity and, therefore, it was just disappointing that we couldn’t pursue the phase III trial with immunomodulatory agents.


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