Immunotherapy in Hematologic Malignancies

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Immune checkpoint inhibitors targeted against CTLA-4 and PD-1 have demonstrated promising efficacy across solid tumors and hematological malignancies, with FDA approvals for the treatment of metastatic melanoma and advanced lung cancer. These antibodies have demonstrated that reversing the anergic state of the T cells can result in a clinically meaningful benefit, explains Marques Borrello, MD. Other immunotherapy strategies, such as vaccine therapy, are also showing promise, and a variety of approaches are being tested in hematologic malignancies.

Immunomodulatory drugs, such as thalidomide, lenalidomide, and pomalidomide, have changed the landscape of multiple myeloma treatment, states Madhav Dhodapkar, MD. Although these drugs have only minor structural differences, a patient who is resistant to one can still experience an immune system response with another one of these agents. Although it is known that each of these therapies work in part by binding to cereblon, there is still a lot to be learned about these drugs, observes Dhodapkar.

Allogeneic stem cell transplantation (ASCT) is historically the most effective immunotherapy and may be the most effective treatment in acute myeloid leukemia, says Dan Douer, MD. ASCT derives its effectiveness from the donor T-cells reacting against the host leukemia cells. One challenge to transplant includes donor T-cells attacking not only leukemia cells but normal host cells as well, leading to graft-versus-host disease. Although this is a toxicity inherent in ASCT, it is proof of concept that immunotherapy works when using foreign T-cells, says Douer.

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