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CAR T Therapy Case Study Shows Early Success in Treatment of Acute Myeloid Leukemia

CAR T Therapy Case Study Shows Early Success in Treatment of Acute Myeloid Leukemia

There are currently 2 FDA-approved chimeric antigen receptor (CAR) T-cell therapies available in the United States, tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta). Both therapies are indicated to treat adult patients with relapsed or refractory diffuse large B-cell lymphoma; however, Kymriah holds an additional indication to treat B-cell precursor acute lymphoblastic leukemia in certain pediatric and young adult patients.

As part of a report by the American Society of Clinical Oncology, Clinical Cancer Advances 2018, CAR T-cell therapy was named the biggest research breakthrough of 2017. Now, researchers at Moffitt Cancer Center in Tampa, Florida are looking to expand the therapy use to other cancers.

In a new phase 1 trial called THINK (Therapeutic Immunotherapy with Natural Killer Group 2D [NKG2D]), published online in Haematologica, researchers are investigating Celyad’s new CAR T therapy CYAD-01 in the treatment of acute myeloid leukemia (AML). While more than half of patients with AML go into remission after treatment with chemotherapy, many relapse due to residual leukemia cells evading both chemotherapy and the immune system. CYAD-01 genetically modifies the patients’ immune cells to express a natural killer receptor that targets leukemia cells.

A 52-year-old male patient with wild-type AML was enrolled in the THINK trial after receiving initial treatment and relapsing. CYAD-01 treatment was well-tolerated by the patient with non-related adverse events. On disease evaluation day 197 post CYAD-01 treatment, the patient had achieved complete molecular remission. To date, the AML patient has remained cancer-free for 9 months after treatment with CYAD-01, followed by a bone marrow transplant.

“It is important to note that this is the first time CAR T has induced a remission in AML. It is also the first time CAR T has been effective without the need of preconditioning chemotherapy,” said David Sallman, MD, assistant member of the department of malignant hematology at Moffitt and the case study author.

With CAR T-cell treatment, T cells are removed from a patient’s blood and then genetically modified to enable the cells to identify and specifically attack cancer cells. Once the new cells are developed, patients typically receive preconditioning chemotherapy in order to deplete their immune system and make room for the new cells. However, in the THINK study, no preconditioning chemotherapy was necessary.

“Our case study shows that CAR T therapy is a viable option for AML patients,” added Sallman. “We now need to take what we have learned in this initial study and expand the trial.”

Reference

Sallman D, Brayer J, Sagatys E, et al. NKG2D-based chimeric antigen receptor therapy induced remission in a relapsed/refractory acute myeloid leukemia patient [published online April 27, 2018]. Haematologica. doi:10.3324/haematol.2017.186742.

Originally posted on AJMC.com

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