Minnesota Oncology

Dose-Dense R-CHOP plus Zevalin Improves Response in Diffuse Large B-Cell Lymphoma

Dose-dense R-CHOP followed by Zevalin® (ibritumomab tiuxetan) converts partial responses to complete responses and maintains durable responses in patients with untreated diffuse large B-cell lymphoma, according to the results of a study presented at the 52nd annual meeting of the American Society of Hematology (ASH) in Orlando, Florida.

Non-Hodgkin’s lymphoma (NHL) refers to a group of cancers that originate in different cells of the immune system. Diffuse large B-cell NHL is a common type of NHL that affects immune cells called B-cells; it is considered an aggressive type of NHL.

Standard treatment for DLBCL typically includes R-CHOP, which refers to treatment with the monoclonal antibody Rituxan® (rituxamab) plus cyclophosphamide/Adriamycin/vincristine/prednisone (CHOP). Although this regimen has led to improved outcomes, there is a group of poor-risk patients who need an alternative treatment strategy.

Zevalin is a type of radioimmunotherapy treatment (RIT) that combines the monoclonal antibody Rituxan with Zevalin, which is comprised of an anti-CD20 monoclonal antibody and Yttrium-90, a radioisotope that delivers the radiation. When injected into the body, Zevalin attaches to a protein (CD20) found only on the surface of B-lymphcytes, such as cancerous B-cells found in many forms of non-Hodgkin’s lymphoma. The radioactivity that is spontaneously emitted targets the B-cell and destroys it. This approach protects healthy tissue.

Zevalin has been shown to be a highly effective treatment-and has the added benefit of being administered over a single short period of time. Zevalin is administered on an outpatient basis and the total duration of therapy is less than 10 days.  Zevalin offers active patients the opportunity to spend less time undergoing treatment than more conventional chemotherapy.

Dose-dense R-CHOP refers to treatment that is delivered every 14 days instead of every 21 days. This condensed treatment schedule intensifies the treatment. Researchers conducted a study to evaluate dose-dense R-CHOP followed by consolidation treatment with Zevalin in 20 patients with stages II-IV DLBCL. The median age of patients was 60 (range 33-81) and all patients were previously untreated.

Eighteen patients completed six cycles of R-CHOP and 16 went on to Zevalin consolidation. All 20 patients received 4 or more cycles of R-CHOP alone—and the overall response rate was 100 percent with a 75 percent complete response rate and a 25 percent partial response rate. All four patients who stopped treatment with dose-dense R-CHOP remained in complete response.

Among patients who received Zevalin, three patients converted from partial response to complete response, maintaining an overall response rate of 100 percent and complete response of 90 percent and partial response of 10 percent. The most common grade 3/4 toxicity was neutropenia, which occurred in 50 percent of patients, with no cases of neutropenic fever.

The researchers concluded that consolidation with Zevalin after dose-dense R-CHOP converts partial responses to complete responses and maintains durable responses with acceptable toxicity in patients with untreated DLBCL.

Reference:

Karmali R, Manson A, Bueschel K, et al. Phase II study of 2-weekly CHOP+Rituximab followed by yttrium-90 ibritumomab tiuxetan (Zevalin) in patietns with previously untreated diffuse large B cell lymphoma (DLBCL): Final analysis. Blood. 2010; 116(21): Abstract 3947.

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