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CAR T Cell Breakthrough Announced at ASH 2015
Posted: Dec 06, 2015
CAR T Cell Breakthrough Announced at ASH 2015 image

BY PAT KILLINGSWORTH - MCRI PATIENT ADVISORY BOARD Exciting new therapy news from the American Society of Hematology (ASH) meetings in Orlando this weekend. Data from a small, Phase 1 Study released Saturday boosts hopes that T cell immunotherapy may be the wave of the future. According to the publication, HemOnc Today, given in high enough doses, modified CAR T cell therapy was able to control a pair of heavily pretreated patient’s multiple myeloma. This brief excerpt from the article helps explain things better than I ever could:

B-cell maturation antigen (BCMA) is expressed by normal and malignant plasma cells, according to study background. James N. Kochenderfer, MD, investigator in the experimental transplantation and immunology branch of the NCI’s Center for Cancer Research, and colleagues conducted a first-in-humans clinical trial using autologous T cells modified with a gamma-retroviral vector to express anti-BCMA chimeric antigen receptors (CAR). “B-cell maturation antigen is expressed in many cases of multiple myeloma,” Kochenderfer told HemOnc Today. “The CAR gives the T cells the ability to recognize a specific target on malignant cells.” The study included data from 12 patients with advanced multiple myeloma (median prior therapy lines, 7). Patients received a chemotherapy regimen of cyclophosphamide (300 mg/m2) and fludarabine (30 mg/m2) for 3 days, followed by a single infusion of CAR-modified T cells at one of four dose levels (0.3x106, 1x106, 3x106 or 9x106 CAR-positive T cells/kg of body weight)…

As dosing was escalated, results improved. Check this out:

The first patient had multiple myeloma that comprised up to 90% of total bone marrow cells prior to treatment. Beginning 4 hours following infusion, the patient experienced cytokine release syndrome and had a neutrophil count below 500/μL, which persisted for 40 days after infusion prior to recovery. According to the researchers, this patient’s myeloma was rapidly eliminated following infusion, with bone marrow plasma cells decreasing to 0% 1 month after treatment. The patient’s serum M-protein was undetectable 2 months after treatment, with serum and urine immunofixation electrophoresis tests negative after 2 months. The patient is currently in stringent complete remission. “The elimination of multiple myeloma was quite impressive, given the advanced status of this patient’s disease,” Kochenderfer said in an interview. The second patient treated with the highest dose had multiple myeloma with 80% bone marrow plasma cells prior to treatment and also experienced cytokine release syndrome. The patient’s M-protein decreased from 3.6 g/dL before treatment to 0.8 g/dL 4 weeks after treatment. Further, the patient’s serum lambda free light chain decreased from 95.9 mg/dL prior to treatment to 0.15 mg/dL 4 weeks after treatments. Bone marrow plasma cells were undetectable 4 weeks after infusion…

Other patients responded, just not as impressively. Is that because their dosing was at lower levels? Common sense says, “Yes.” But twelve patients aren’t enough to draw any definitive conclusions. Even so, it’s hard to argue that these preliminary results are encouraging. Researchers are so excited about the early results that plans are already being made to open expanded clinical trials in a matter of months. Read more: Anti-B-cell-maturation antigen CAR T cells show promise for advanced multiple myeloma  

The author Jennifer Ahlstrom

about the author
Jennifer Ahlstrom

Myeloma survivor, patient advocate, wife, mom of 6. Believer that patients can contribute to cures by joining HealthTree Cure Hub and joining clinical research. Founder and CEO of HealthTree Foundation. 

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