51成人动漫

CHICAGO -- Engineered immune cells showed promise in relapsed and refractory multiple myeloma, with two studies demonstrating impressive, but early, results.

Researchers from China reported that T cells modified to track and kill multiple myeloma cells had led to responses in 33 of 35 patients treated so far, including several long-lasting stringent complete responses.

And in a poster discussion, U.S. researchers said that a similar product led to clinical responses in 15 of 18 treated patients.

Both studies were presented at the In a late-breaking presentation at the American Society of Clinical Oncology annual meeting.

CAR (chimeric antigen receptor) T cells are the ultimate in personalized medicine: clinicians harvest immune cells from a patient, modify them in the lab so they recognize a target protein, and re-infuse them.

The cell products that are furthest along target a protein called CD19, which is expressed on the surface of B cells; they have shown promise in acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and B-cell non-Hodgkin's lymphomas.

But the products now being tested for multiple myeloma target a different protein -- B-cell maturation antigen (BCMA) -- that is more narrowly expressed than CD19. "We think this is the right target," said Noopur Raje, MD of Massachusetts General Hospital Cancer Center in Boston, who is part of the research group whose poster was discussed here.

"The majority of myeloma patients are going to express BCMA," she told 51成人动漫.

Because the antigen is not widely expressed, T cells targeting BCMA are less likely to cause adverse events, commented Sagar Lonial, MD, of Emory University in Atlanta. It's not like other cellular proteins, he told 51成人动漫, "where there can be off-target expression of the same antigen."

The data from the Chinese researchers is the most mature so far; they've treated 35 patients and have at least 4 months of follow-up on 19 who reached a very good partial response -- a consensus cut-off for assessing efficacy from the International Myeloma Working Group.

Of those 19, one relapsed with an extra-medullary lesion after the very good partial response and 14 have gone on to achieve a stringent complete response, Wanhong Zhao, MD, PhD, of the Second Affiliated Hospital of Xi'an Jiaotong University in Xi'an, China, told reporters here.

No patient who reached a stringent complete response has relapsed, Zhao said, and the five who have been followed for more than a year also are free of minimal residual disease -- they have no detectable cancer cells in their bone marrow.

The durability and completeness of the responses "raise hopes of a cure," Zhao said.

As well as apparent efficacy, the process appeared to be safe, he said. The major adverse event associated with CAR T cells is cytokine release syndrome, which is associated with fever, low blood pressure, and difficulty breathing and can be life threatening.

So far, 85% of patients have had such a syndrome, but most were mild and transient, Zhao said. The two patients with grade 3 cytokine release syndrome (CRS) were successfully treated with tocilizumab (Actemra). There have been no cases of neurological complications, such as cerebral edema.

The science behind the trial "is really getting to be quite revolutionary," commented ASCO expert Michael Sabel, MD, of the University of Michigan in Ann Arbor.

"We are now seeing the merger of immunotherapy and precision," he said. "This is really the epitome of personalized medicine." Sabel added that more research is needed, not just to extend and validate the results of the study so far but also "in terms of making the technology more accessible to a wider array of patients."

The other study, referred to as the Bluebird trial, the researchers were testing a range of doses, and found that when patients got more than 150 million modified cells, all 15 responded -- four with complete responses, seven with very good partial responses, and four with partial responses.

Among the three patients who got the lowest dose -- 50 million cells -- one patient progressed, one had stable disease, and one had a partial responses.

Fifteen of the 21 patients developed CRS but most cases were grades 1 and 2, with only two grade 3 cases that resolved within 24 hours. Four patients were given tocilizumab (Actemra) and one got steroids.