City of Hope Physicians and Scientists Present Trailblazing Research at Annual ASCO Meeting
June 2, 2017 | by Letisia Marquez
American Society of Clinical Oncology’s (ASCO) 2017 Annual Meeting June 2 to 6. More than 38,000 oncology professionals and others will attend the conference to learn about the latest scientific advancements in cancer treatment, detection and prevention.
“The annual ASCO conference brings together the brightest minds in the international cancer community to announce exciting, new research discoveries and discuss the most effective treatments and prevention efforts,” said Steven T. Rosen, M.D., Irell & Manella Cancer Center Director’s Distinguished Chair and City of Hope’s provost and chief scientific officer. “City of Hope patients benefit from the latest research and discussions that are shared at the ASCO meeting as an important part of our commitment to saving lives, fighting cancer and finding better cures.”
Here’s a look at some of the leading-edge research being presented at ASCO:
Allogeneic stem cell transplants for HIV-infected patients
Because of persisting immune system abnormalities, even effectively treated HIV-infected patients are at a much higher risk of developing blood cancers, like acute leukemias and lymphomas. Patients with HIV infection have a risk of blood cancers that may be up to 25 times higher than uninfected individuals.
Joseph Alvarnas, M.D., City of Hope director of value based analytics and an associate clinical professor in the Department of Hematology & Hematopoietic Cell Transplantation.
For many patients, however, effective treatment of their leukemia or lymphoma requires a different kind of blood stem cell transplant: an allogeneic transplant that uses a matched sibling or unrelated individual as the stem cell donor, Alvarnas added. HIV infection has been traditionally viewed as an absolute disqualification for this type of transplant. Blood and marrow transplants are used to treat patients with blood cancers, but using this treatment approach for HIV patients has been regarded as too risky due to the presumed higher risk of fatal infections.
A study led by City of Hope investigators working in collaboration with the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) changes this paradigm.
In the BMT CTN trial, 17 HIV-infected patients – who also had either acute leukemia, high-risk myelodysplastic syndromes, Hodgkin lymphoma or non-Hodgkin lymphoma – received transplants from either matched sibling or unrelated donors. Eight patients received full-intensity chemotherapy and/or radiation therapy, while seven received reduced-intensity chemotherapy prior to transplant to help eradicate their blood cancer cells and prepare the recipient to receive the donor cells.
The trial was designed to determine the safety of transplant for HIV-infected patients. The primary study end-point was mortality due to the transplant measured at 100 days. In addition to assessing early survival, patients were assessed for late survival, control of HIV infection and recovery of T cell immunity after transplant.
At the 100-day mark, all patients had survived the transplant. Thirteen patients were in complete remission, and four patients had a blood disease that had returned or worsened. Eight patients achieved “complete chimerism,” such that only their donors’ DNA was measured in their blood or marrow.
At one year, overall survival was 57 percent. Eight patients died due to relapse or progression of their blood cancer or due to therapy-related toxic effects like graft-versus-host disease, adult respiratory distress syndrome and liver failure.
Based upon the study not demonstrating an increased risk of death over that expected for non-HIV-infected patients, the authors of the trial concluded that allogeneic blood stem cell transplant “should be considered the standard of care for HIV patients who meet usual eligibility criteria.”
City of Hope was one of the leading accruing institutions in the trial, and Alvarnas served as the study’s senior author. The trial was performed in collaboration with the AIDS Malignancy Consortium and funded by the National Heart, Lung, and Blood Institute.
Acute lymphoblastic leukemia patients experienced fewer side effects with immunotherapy drug than chemotherapy
Blinatumomab is an immunotherapy drug that can work against relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). But what types of side effects does the drug cause as compared to standard-of-care chemotherapy?
Anthony Stein, M.D., co-director of the City of Hope Gehr Family Center for Leukemia Research and clinical professor of hematology and hematopoietic cell transplantation, 405 patients received either standard-of-care chemotherapy or blinatumomab – which can activate a person’s own disease-fighting T cells to attack the leukemic cells – as an intravenous infusion for up to five cycles. Each cycle lasted 28 continuous days with two weeks off the treatment.
The trial took place across 101 medical centers in 21 countries.
Patients who received blinatumomab had fewer fevers, less anemia, lower platelet counts and lower white blood cell counts than those who had chemotherapy. Blinatumomab patients also had fewer neurologic side effects and experienced fewer infections compared with chemotherapy patients.
Cytokine release syndrome, or a fever that occurs due to the immunotherapy drug, was more frequently reported in blinatumomab patients than in chemotherapy patients.
“Blinatumomab has emerged as a better treatment option for many ALL patients and with less severe side effects,” said Stein, noting that previous trial results published in the New England Journal of Medicine demonstrated a 36 percent complete remission rate for blinatumomab patients and 16 percent for chemotherapy patients after 12 weeks of treatment. Median overall survival was 7.7 months versus four months, respectively. “Blinatumomab causes side effects that are manageable, so this is very hopeful news for ALL patients.”
Effective treatment for older adults with metastatic breast cancer
In the past, many clinical trials have excluded older patients or only included a small number of them. Oftentimes, it’s unknown how their cancer will respond to chemotherapy and other cancer treatments, and what the side effects will be. A phase 2 City of Hope-led clinical trial targeted adults over the age of 65 who had metastatic breast cancer and took the chemotherapy drug nab-paclitaxel, to assess how well they tolerated and responded to the drug. A geriatric assessment and toxicity calculator were also key components of the trial.
Arti Hurria, M.D., the George Tsai Family Chair in Geriatric Oncology, and colleagues, the geriatric assessment was then used to calculate a “toxicity risk score,” or the drug’s impact on a patient’s body.
For the study, 40 City of Hope and Ohio State University Comprehensive Cancer Center patients (mean age 73) received an average of six cycles of nab-paclitaxel (each cycle was given for three weeks straight and then the patient had one week off). Patients were closely monitored for side effects such as neuropathy, or the loss of feeling in the hands and feet.
A third of the patients had a complete or partial response to the drug, or their cancerous tumors reduced in size. There were no cases of severe neuropathy. Although 13 patients were hospitalized during the trial, the toxicity risk score helped doctors predict which patients would require hospitalization, as well as which would potentially have better health outcomes during chemotherapy.
“One of the most interesting findings is that patients who had a high toxicity risk score using our calculator were most likely to experience severe toxicity than those with a low toxicity score,” said
Enrique Soto-Perez-de-Celis, a City of Hope fellow who is the study’s first author. “By using the geriatric assessment and toxicity risk score, doctors can help weigh the risks and benefits of therapies in older adults.”
A larger City of Hope-led trial enrolling 500 patients is also currently examining how well older adults with breast cancer tolerate several chemotherapy drugs, and also incorporates the geriatric assessment and toxicity risk score.
Soto noted that the Alliance for Clinical Trials is already incorporating the geriatric assessment into some of their trials.
COH29 trial featured at ASCO
An ongoing phase 1 trial that features COH29, a promising cancer drug being developed at City of Hope, will be featured as an ASCO trials-in-progress abstract. Joseph Chao, M.D., an assistant clinical professor in the Department of Medical Oncology & Therapeutics Research, will discuss the trial, which is enrolling patients with solid tumors, including breast, colon, ovarian, pancreatic, stomach and lung cancers. Patients whose disease is treatment-resistant to standard therapies, or for which no other treatment options exist, are eligible for the trial.
City of Hope has conducted preclinical studies with the chemotherapy drug, which inhibits activity of an enzyme called ribonucleotide reductase (RNR), thus preventing cancer cells from copying themselves and dividing. By designing the drug to better target RNR, researchers also hope that COH29 will produce fewer side effects than other chemotherapy drugs currently available, and that cancer cells are less likely to develop resistance to the agent.
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