In an oral presentation at the 10th International Conference on Malignant Lymphoma in Lugano, Switzerland, Paul A. Hamlin, M.D., of Memorial Sloan-Kettering Cancer Center, presented results of an investigator-sponsored trial of the investigational regimen consolidating rituximab-CHOP (R-CHOP) with 90Yttrium Ibritumomab Tiuxetan (Zevalin) radioimmunotherapy in high risk, elderly patients with previously untreated high-intermediate and high risk diffuse large B-cell lymphoma (DLBCL). Cell Therapeutics markets Zevalin in the United States.
"In a high risk, elderly patient population with significant comorbidities, sequential R-CHOP followed by radioimmunotherapy resulted in excellent complete response and overall and progression-free survival rates," concluded Hamlin. "This approach is now the focus of an international phase III study."
Drug Clinical Trials
"Improvement of relapse-free survival in these patients is an important unmet need since the outcome is poor for patients who relapse with this disease and who cannot tolerate intensive salvage therapy and stem cell transplantation," said Jack W. Singer, M.D., Chief Medical Officer at CTI. "The survival data from this study are highly encouraging compared to historical data and provide the rationale for a registration-directed randomized trial of Zevalin consolidation in higher risk patients with DLBCL."
Results of the Study
Historical studies provided as background in the presentation indicate that approximately 50 percent of elderly patients with high risk diffuse large B-cell lymphoma (DLBCL) relapse after treatment with R-CHOP. Treatment options for patients who are ineligible for autologous stem cell transplant are limited. In this analysis, of the 63 patients enrolled on the study, 39 patients had been treated with Zevalin. The median age is 75 years (range 62-86); Karnofsky performance status was <80 percent in 59 percent of patients with a median performance status of 70 percent; prognostic score was high-intermediate/high in 53 percent and 47 percent of patients, respectively. Moderate or high impact comorbidity is present in 86 percent. In the intent-to-treat population, progression-free (PFS) and overall survival (OS) were 59 percent and 65 percent, respectively, at 22 months. In the 39 patients who received Zevalin, PFS and OS were 78 percent and 82 percent, respectively, at 26 months.
Responses improved in 11 patients who received Zevalin, with eight patients improving from an unconfirmed (CRu) to a confirmed complete response (CR) and three patients improving from a partial response (PR) to a CR/CRu. The side effects reported included blood count suppression: 26 percent and 36 percent grade 3/4 neutropenia, 15 percent grade 3 anemia, and 36 percent and 31 percent grade 3/4 thrombocytopenia. Six patients had delayed blood count recovery for more than 12 weeks. One patient developed myelodysplasia and two patients died after Zevalin was given, one from a suspected brain hemorrhage and one from congestive heart failure.