Research on chimeric antigen receptor (CAR) T-cell therapy to be presented at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition is set to address drawbacks associated with such treatment, such as time, expense, and toxicity, according to Robert A. Brodsky, MD.
“CAR T-cells have captured the imagination of physician scientists and patients alike, mainly for their incredible efficacy in treating B-cell malignancies like acute lymphocytic leukemia and non-Hodgkin lymphomas,” Brodsky, who serves as secretary of ASH and is also the director of the division of hematology at Johns Hopkins Medicine, said in a preview presscast ahead of the meeting.
“But there have been several drawbacks of CAR T-cells. One of them is the time and expense that it takes to generate a CAR T-cell for a specific patient. Only about two-thirds of patients enrolled in CAR T-cell trials will actually get the infusion because often the disease will progress during the time that it takes to make a successful product.
At the upcoming ASH Annual Meeting & Exposition, being held from December 7-10 in Orlando, Florida, 3 presentations will focus on CAR T-cell therapy advances that could be practice changing in the future.
One of the trials Brodsky focused on in the presscast was the phase Ib/II CARTITUDE study of JNJ-4528 – a CAR T-cell that is directed against B-cell maturation antigen (BCMA) in patients with relapsed/refractory multiple myeloma.
“The B-cell maturation antigen is expressed on B-cells, but it is also on all malignant plasma cells,” he explained.
The trial was conducted in 25 patients who received chemotherapy first, followed by CAR T-cell infusion.
Although the follow-up was only 3 months, Brodsky noted, 91% of the patients responded to the CAR T-cell product. Moreover, 2 of the patients experienced complete remission.
“The other responses were very deep responses. So, very promising early results,” Brodsky concluded.
Deepu Madduri, MD, from Icahn School of Medicine at Mount Sinai, will be presenting this at the meeting.
Phase I Dose-Climbing Trial
A trial that was done in China, describes a bi-specific CAR T-cell therapy targeting BCMA and CD38, which is also on the malignant plasma cell, Brodsky pointed out, for the treatment of 16 patients with relapsed/refractory multiple myeloma.
“The idea here is to try and prevent resistance to the CAR T-cells by targeting 2 different antigens at the same time,” he explained.
After a median follow-up of 36 weeks, 87.5% of patients responded to treatment and 9-month progression free survival was 75%. Moreover, the product was well tolerated.
“It’s still early, but again, this is very promising data in multiple myeloma with using CAR T-cell (therapy),” Brodsky said.
The study Brodsky found most exciting is one evaluating mosunetuzumab, and off-the-shelf product for the treatment of 218 patients with poor prognosis non-Hodgkin lymphoma, including those who are relapsed/refractory to treatment with CAR T-cell therapy and are in active treatment through multiple lines of therapy. Twenty-three patients already received CAR T-cell therapy.
“Now, this is not a CAR T-cell. This is a bi-specific antibody that targets both CD3 and CD20,” Brodsky explained. “So, the concept here is that this monoclonal antibody engages T cells and directs their cytotoxicity against B cells. It’s basically an antibody using the patients own T cell to do what a CAR T-cell would do.”
Sixty-four percent of patients responded to treatment with Mosunetuzumab, and 42% of patients experienced a complete response. Moreover, the median duration of response is out to 9 months.
Because this is an off-the-shelf product, it negates the issue surrounding time to generate the product and will likely be much cheaper than CAR T-cell therapy. “And from the preliminary results it looks like it is much less toxic.”
This trial will be presented by Stephen J. Schuster, MD, from the Abramson Cancer Center, University of Pennsylvania, during the meetings Plenary Session.