December 6, 2015 | by Elise Lamar
Cancer researchers increasingly realize that drug combinations, as opposed to single drugs, may be the best treatment approach. If so, some are asking, why not entirely different treatment regimens to create the ultimate weapon against tumors? City of Hope researchers are addressing that possibility by combining two approaches at which they excel - bone marrow transplant and immunotherapy - as a way to treat recurrent blood cancers.
As a first step, they reported success of a relevant phase 1 safety trial at the annual meeting of the American Society of Hematology (ASH), held in December in Orlando. There, City of Hope hematologist Leslie Popplewell, M.D., the trial’s principal investigator, reported outcomes following treatment of patients with recurrent non-Hodgkin lymphoma. The patients first received a bone marrow transplant and then, two days later, an infusion of their own genetically modified T cells, an immunotherapy procedure called adoptive cell transfer. The treatment proved safe overall, and many patients participating in the trial are still being monitored for treatment efficacy.
“Autologous stem cell transplantation is the standard treatment for aggressive B-cell lymphoma that relapses after primary therapy, but not every patient will be cured, even with this aggressive therapy,” says Popplewell. “This study encourages us to move forward by adding cellular immunotherapy to this standard approach.”
Immunotherapy, hailed by some as one of the most significant medical breakthroughs of the last decade, is broadly defined as any therapeutic approach, be it via vaccination or immune cell transfer, that rallies a patient’s immune system to attack a tumor. In the case of adoptive cell transfer, which was employed in the recent trial, researchers harvest a lymphoma patient’s T cells, genetically modify them to express receptors zeroing in on a patient’s tumor, and then reinfuse the patient with the newly armed cells in hopes that they eradicate cancerous cells.
The decision to add immunotherapy to the standard transplant regimen emerged from the fact that many patients with recurrent non-Hodgkin lymphoma initially respond positively to blood stem cell transplant but then relapse. The trial team, which included investigators from City of Hope and the Fred Hutchinson Cancer Research Center in Seattle, reasoned that supplementing transplant patients with infusions of tumor-killing T cells might increase remission rate.
For the phase 1 trial, the team administered two versions of T cells harboring slightly different receptor proteins to two groups of eight patients, all with either diffuse large B cell (DLBCL) or mantle cell (MCL) lymphoma. Both variations proved safe overall, and patients showed few signs of toxicity, even at high T cell doses. The study authors conclude that the treatment is safe in high-risk transplant patients and are now making minor modifications in the protocol to prepare for more stringent tests of treatment efficacy.
“Immunotherapy is clearly an area of tremendous potential for treating cancer,” said Stephen J. Forman, M.D., leader of the Hematologic Malignancies and Stem Cell Transplantation Institute and director of the T Cell Immunotherapy Laboratory at City of Hope. Forman, the Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation, was a co-corresponding author of the study. “We’re proud and excited to be among the few teams in the country working on this type of immunotherapy and to have the opportunity to offer these therapies to our patients through clinical trials.”
City of Hope's Hematologic Malignancies and Stem Cell Transplantation Institute is one of the largest transplant centers in the world and has pioneered novel transplant approaches for leukemia and lymphoma patients. Successful integration of immunotherapy with these regimes could enhance patient survival and ultimately improve quality of life for patients other cancers.
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