Recent studies indicate the high efficacy of novel immunotherapies for relapsed or refractory hematological malignancy patients.
At the last ASH Annual Meeting and Exposition, held in early December, new and promising treatments for hematological malignancies, with the potential to significantly boost recovery rates, were presented. The above treatments are already offered at Sheba Medical Center.
One of the novel treatments presented at the conference was KTE-X19, a chimeric antigen receptor CAR T-cell therapy designed to treat mantle cell lymphoma. CAR T-cell therapy involves collecting T-cells from the patient’s blood with a device similar to a dialysis machine. The collected cells are then genetically modified to produce receptors that target an antigen present on the surface of the cancer cell envelope, enabling them to recognize and eliminate the cancer cells. The engineered cells are multiplied under laboratory conditions, and when there are enough of them, they are injected back into the patient. The modified CAR T-cells continue to multiply in the patient’s body, identify the cancer cells, and secrete compounds that destroy them.
“Until recently, the only treatment we could offer to mantle cell lymphoma patients whose disease had relapsed was a bone marrow transplant, which is a complicated, high risk procedure that is suitable for patients up to age 65,” says Dr. Abraham Avigdor, Director of the Institute of Hematology at Sheba Medical Center, who explains: “CAR T-cell therapy teaches the immune system to recognize the malignant cells and attack them. This is a real breakthrough for patients with hemato-oncological diseases.” Prof. Arnon Nagler, President of the Division of Hematology at Sheba and a world-renowned expert in the field of CAR T-cell therapy, adds: “Sheba Medical Center is one of only a few institutions around the world that offer CAR T-cell therapy for leukemia, some types of lymphoma and multiple myeloma. Sheba has the most extensive experience in providing this treatment not only in Israel, but also among European institutions … Sheba enjoys a great advantage by having CAR T-cells produced in-house in its state-of-the-art specialized laboratory, so the whole treatment process is carried out under one roof, and takes only around 10 days from start to finish.” More than 200 patients have undergone CAR T-cell therapy at Sheba so far, including about 60 children.
Among 68 patients who participated in a Sheba CAR T-cell therapy study, over half showed complete remission after treatment. The participants all previously received two lines of treatment and were thought to have a very poor prognosis.
Another treatment presented at the American Society of Hematology Annual Meeting and Exposition involves the use of bispecific monoclonal antibodies. The treatment introduces artificial antibodies to the bloodstream via intravenous infusion. One of the antibody’s arms binds to a specific protein (CD3) found on the surface of T-cells, and another to a protein (CD20) which is found on the surface of cancerous B-cells. “In this way, the antibody binds the T-cells of the immune system to the lymphoma cells, so that later they secrete substances (cytokines) that attack the lymphoma,” explains Dr. Avigdor.
Dr. Avigdor is part of the Sheba team running a study on the bispecific monoclonal antibody Mosunetuzumab. 29 patients, aged 67-100, with aggressive large B-cell lymphoma, participated. Due to their age, the participants’ bodies would have been unable to cope with the side effects of chemotherapy. According to Avigdor: “The study is in its early stages, but the results are very impressive. The treatment has been shown to be very safe, with no significant side effects. Although these are preliminary results, they are very encouraging and raise the possibility that in the future we will be able to use advanced immunotherapy to replace chemotherapy. To me, this is a real breakthrough.”