ATLANTA, Dec. 12 /PRNewswire/ -- Elderly patients with advanced acute myeloid leukemia, high-risk myelodysplastic syndrome, or relapsed/refractory non-Hodgkin lymphoma generally do not undergo intense, high-dose therapy due to perceived age-related risk. However, innovative therapies that combine cancer-fighting antibodies and radiation may provide hope for this patient population, according to two new studies presented today at the 47th Annual Meeting of the American Society of Hematology.
“We want to provide elderly patients with the best chance of survival after cancer treatment regardless of their age and disease,” said Stanley Schrier, M.D., Stanford University School of Medicine, Stanford, Calif. “Creating novel therapeutic approaches breaks the limitations of age for cancer survivorship.”
A Phase II Study of Myeloablative I-131-Anti CD-20 (Tositumomab) Radio- Immunotherapy and Autologous Hematopoietic Stem Cell Transplantation (ASCT) for Adults 60+ Years of Age With High-Risk Relapsed or Refractory B-Cell Lymphoma [Abstract 487]
Non-Hodgkin lymphoma (NHL) is a cancer of the lymph nodes, which play an important role in the immune system by destroying infectious organisms. But with NHL, lymphoma cells divide and grow uncontrollably, and may spread to other parts of the body, such as the bone marrow. Over time, lymphoma cells may replace the normal cells in the bone marrow, causing infections and bleeding and making it harder for the body to produce blood cells.
The majority of patients with relapsed or refractory B-cell NHL are older than 60 years of age. Many of these patients are denied potentially curative high-dose regimens due to concerns about the excessive toxicity associated with stem cell transplantation. Myeloablative I-131-anti CD-20 (tositumomab) is a monoclonal antibody that contains a radioactive substance (iodine-131). It belongs to a class of drugs called radioimmunotherapy agents, and is directed to the CD-20 receptor located on B lymphocyte cells (B-cells). This receptor is found on some normal lymphocytes, as well as those that are cancerous.
A phase II trial conducted at the University of Washington and Fred Hutchinson Cancer Research Center in Seattle, Wash., found that tositumomab can deliver beneficial radiation doses to tumors while limiting exposure to normal organs, which is ideal for older adults requiring high-dose therapy, as well as other highly compromised patients. Tositumomab attaches to the CD-20 receptor and kills the cells by exposing them to a radioactive agent. Although the drug targets both normal and cancerous cells, one can live without normal B-cells, as they are eventually repopulated by the stem cell transplant.
In this trial, 24 patients with relapsed or refractory B-cell NHL aged 60 years or older were treated with high-dose radiation (tositumomab) and autologous hematopoietic stem cell transplantation (ASCT), a procedure in which stem cells from a patient’s own blood, bone marrow, or other tissue are transplanted. Patients with an enlarged spleen or large tumor bulk were required to undergo further treatment in order to optimize radiation efficacy. Patients were followed after ASCT for a median of 2.2 years, ranging from one month to 4.9 years. The estimated four-year survival rate was 55 percent, while the estimated four-year progression-free survival rate was 37 percent. Overall, the therapy was well tolerated with no treatment-related deaths and no grade 3-4 Bearman toxicity (life-threatening or fatal toxicity occurring within 100 days of ASCT).
“Tositumomab can deliver potentially curative radiation doses to tumor sites while limiting exposure to normal organs,” said Ajay K. Gopal, M.D., University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Wash. “When used with autologous hematopoietic stem cell transplantation, it is a well-tolerated and effective transplant option for older adults requiring high-dose therapy for B-cell non-Hodgkin lymphoma. Further follow-up and additional patients will help confirm the durability of these findings.”
131I-Anti-CD45 Antibody Plus Fludarabine, Low-Dose Total Body Irradiation and Peripheral Blood Stem Cell Infusion for Elderly Patients With Advanced Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS) [Abstract 397]
Acute myeloid leukemia (AML) is cancer of the blood and bone marrow. In AML, large amounts of abnormal white blood cells are produced and drive out the normal white blood cells in the bone marrow, causing an increased number of infections. High-risk myelodysplastic syndrome (MDS), a group of disorders in which the bone marrow does not produce enough blood cells, is most common among adults over age 60 and often develops into AML.
Elderly patients with advanced AML or high-risk MDS experience a poor survival rate following chemotherapy and have a poor tolerance for high-dose regimens employed in conventional stem cell transplant approaches that are used to eradicate disease. However, hematologists have generated recent successes following infusion of allogeneic peripheral blood stem cells (PBSC) in these patients. The reduced-intensity transplant for older, high-risk patients may lead to a safely induced graft-versus-leukemia (GVL) effect - the immunological rejection of leukemia cells following bone marrow transplantation - with minimal transplant-related deaths. However, GVL effects appear to be most potent in high-risk patients who have a small amount of cancer cells present in the body at the time of transplant.
A phase I clinical trial was conducted by researchers at the Fred Hutchinson Cancer Research Center in Seattle, Wash., to determine the feasibility and safety of targeted radiation therapy to reduce the burden of disease before an established reduced-intensity chemoradiotherapy transplant was used to allow for a GVL effect. The study was designed to estimate the maximum tolerated dose of 131I-anti-CD45 antibody when combined with fludarabine (FLU) and low-dose total body irradiation (TBI). Low-dose TBI is sometimes used to treat disorders of the blood cells and does not require bone marrow or stem cell transplants.
Thirty-three patients older than 50 years of age with advanced AML (24 patients) or high-risk MDS (nine patients) participated in the study. The irradiation treatment produced remission in every patient, all of whom had complete donor-cell engraftment after four weeks. Fifty-five percent of patients survived disease-free for two to 16 months after transplant. Twenty- seven percent of patients experienced disease relapse by month 38 following the transplant.
“The low survival rate of elderly patients following standard chemotherapy regimens, coupled with poor tolerance to high-dose transplant regimens, creates a significant need for an innovative therapeutic approach for this patient population,” said John Pagel, M.D., Ph.D., University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Wash. “Our study findings suggest that this targeted radiotherapy, combined with a standard reduced-intensity transplant regimen, may result in improved outcomes of survival for older, high-risk AML and MDS patients.”
The American Society of Hematology (www.hematology.org) is the world’s largest professional society concerned with the causes and treatment of blood disorders. Its mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems, by promoting research, clinical care, education, training, and advocacy in hematology.
The American Society of Hematology
CONTACT: Leslie Priest of Spectrum Science Communications for The AmericanSociety of Hematology, +1-202-955-6222, or lpriest@spectrumscience.com; orAislinn Raedy of The American Society of Hematology, +1-202-776-0544, oraraedy@hematology.org, or On-site (12/9- 12/13): +1-404-222-5705
Web site: http://www.hematology.org//
