Adding Radioimmunotherapy To Chemotherapy Reduces Relapse Risk In Mantle Cell Leukemia Patients

A new cancer treatment that combines the power of radioactive monoclonal antibodies with high-dose chemotherapy and the patient's own blood stem cells is showing encouraging results in early studies, according to researchers at City of Hope Cancer Center. Results of the clinical trial, conducted on patients with mantle cell lymphoma (MCL), a type of non-Hodgkins lymphoma, were announced today at the American Society of Hematology's 47th annual meeting.

Prognosis of MCL is poor; the disease is usually discovered at an advanced stage, and median survival time is approximately three years.

While MCL patients often initially respond well to treatment, the disease typically returns. For example, in one study more than 90 percent of patients responded to a combination of chemotherapeutic drugs plus a monoclonal antibody (CHOP and Rituxan®), but the median time before relapse was less than 17 months. Other treatment strategies exist, including total body irradiation and high-dose chemotherapy followed by supplementing patients with their own blood stem cells (autologous stem cell transplantation) but relapse rates are still high, up to 50 percent.

The City of Hope-led research team investigated a promising new protocol that added radioimmunotherapy using ZevalinÒ to the therapeutic mix. Zevalin (yttrium-90-ibritumomab tiuexetan) is a monoclonal antibody bound with a cancer-killing radioisotope that specifically targets lymphatic tumors. By itself, Zevalin has shown positive results against MCL, which led the scientists to test it in combination with other treatment modalities.

Two groups of MCL patients were studied. One group included eight patients, each younger than 60 years of age. First, their peripheral blood stem cells were collected, after which they received a high dose of Zevalin followed by the chemotherapeutic drug cyclophosphamide and etoposide. After treatment, their stem cells were returned by infusion.

A second group was comprised of 10 patients. These patients also had their stem cells collected, but received a lower (standard) dose of Zevalin, followed by chemotherapy with BEAM (BCNU, etoposide, cytarabine and melphalan). Their stem cells were also returned by infusion.

At a median follow-up time of 19 months, the study group's estimated two-year overall survival rate is 79 percent, with a disease-free survival rate of 59 percent. No relapses have occurred after the first 12 months.

“These are encouraging results,” said Amrita Krishnan, M.D., physician, Division of Hematology/Bone Marrow Transplantation, City of Hope. “We know that long-term survival for high-risk MCL patients is extremely low with standard therapies, so any improvement we can offer to patients is a positive step. In addition, the Zevalin-based transplant regimens appear to be well tolerated, even in older patients. The apparent plateau in the relapse rate suggests that this approach may lead to durable remissions in patients with high-risk MCL.”

Future research will focus on the Zevalin-BEAM combination. “New modalities such as radioimmunotherapy give us a wider range of treatments with different toxicities and targets. As we refine our strategies, we should be able to increase the efficacy of treatment for challenging diseases such as MCL,” Krishnan said.

City of Hope researchers involved in this study included Amrita Krishnan, M.D., physician, Division of Hematology & Hematopoietic Cell Transplantation; Andrew A. Raubitschek, M.D., physician, Radiation Oncology; Stephen J. Forman, M.D., chair, Division of Hematology & Hematopoietic Cell Transplantation; David Yamauchi, M.D., physician, Diagnostic Radiology; Peter Falk, M.D., co-director, Kaiser Regional Bone Marrow Transplant Program; Leslie Popplewell, M.D., physician, Division of Hematology & Hematopoietic Cell Transplantation; Roberto Rodriguez, M.D., physician, Division of Hematology & Hematopoietic Cell Transplantation; Pablo Parker, M.D., physician, Division of Hematology & Hematopoietic Cell Transplantation; Warren Chow, M.D., physician, Ps Medical Oncology; Ryotaro Nakamura, M.D., physician, Division of Hematology & Hematopoietic Cell Transplantation; Auayporn Nademanee, M.D., physician, Division of Hematology & Hematopoietic Cell Transplantation; and Ricardo Spielberger, M.D., physician, City of Hope - Southern California Kaiser Permanente Regional Bone Marrow Transplantation Program. Researchers also include Henry Fung, M.D., Rush University Medical Center, and Arturo Molina, M.D., Biogen Idec Inc.

About City of Hope

City of Hope is one of the world's leading research and treatment centers for cancer, diabetes, HIV/AIDS and other life-threatening diseases. Named by U.S.News & World Report as one of America's best medical centers for cancer treatment, City of Hope is a pioneer in the fields of bone marrow transplantation and genetics. Founded in 1913, City of Hope is a Comprehensive Cancer Center, the highest designation bestowed by the National Cancer Institute, and a founding member of the National Comprehensive Cancer Network.

City of Hope's scientific knowledge is shared with medical centers locally and globally, helping patients battling life-threatening diseases.

For more information, visit http://www.cityofhope.org.

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