by Gregory M. Vogel
A new cancer treatment that combines the power of radioactive monoclonal antibodies with high-dose chemotherapy and a 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 recently at the American Society of Hematology’s 47th annual meeting in Atlanta.
Prognosis for those with 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 Zevalin® to the therapeutic mix. Zevalin 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 had 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., of the Department of Hematology & Hematopoietic Cell Transplantation (HCT). “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 a 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 Krishnan; Andrew A. Raubitschek, M.D., chair, Department of Cancer Immunotherapeutics & Tumor Immunology; Stephen J. Forman, M.D., chair, and Leslie Popplewell, M.D., Roberto Rodriguez, M.D., Pablo Parker, M.D., Ryotaro Nakamura, M.D., and Auayporn Nademanee, M.D., all of the Department of Hematology & HCT; David Yamauchi, M.D., Department of Diagnostic Radiology; Warren Chow, M.D., the Department of Medical Oncology and Therapeutics Research; and Peter Falk, M.D., co-director, and Ricardo Spielberger, M.D., both of the City of Hope-Southern California Kaiser Permanente Regional Bone Marrow Transplant Program. Other researchers included Henry Fung, M.D., Rush University Medical Center, and Arturo Molina, M.D., Biogen Idec Inc., both former City of Hope physicians.