Single-Agent Rituximab Is Viable Treatment Option for Patients With Lymphocyte- Predominant Hodgkin’s Disease

PHILADELPHIA-Lymphocyte- predominant Hodgkin's disease (LPHD) is a relatively rare form of Hodgkin's disease characterized by the absence of classic Reed-Sternberg cells and the accumulation of large, malignant, mononuclear cells, known as lymphocytic and/or histiocytic cells, in peripheral lymph nodes. These cells are of B-cell lineage and, unique among the other Hodgkin's disease subtypes, express CD20 but do not express CD15 and CD30.[1] Because LPHD comprises only about 5% of all cases of Hodgkin's disease, LPHDspecific therapies have not been developed and LPHD patients enrolled in clinical trials tend to be grouped within larger studies of classic forms of Hodgkin's disease. In general, LPHD has the most favorable prognosis of all Hodgkin's disease subtypes. The clinical course of this lymphocyte-predominant Hodgkin's disease tends to be indolent, and patients often respond well initially to therapy. Complete response rates have been reported to range from 89% to 96% with chemotherapy-based treatment regimens.[1] Relapses are common, however, with approximately 13% to 36% of patients relapsing within a median follow-up of approximately 6 to 7 years.[1] The toxicity associated with radiotherapy or chemotherapy can become significant with repeated treatments upon relapse. According to investiga- tors the use of a B-cell-depleting, anti- CD20 monoclonal antibody such as rituximab(Drug information on rituximab) (Rituxan) may be efficacious in this indication. Rituximab After Relapse Holger Schulz, MD, and colleagues with the German Hodgkin's Lymphoma Study Group are conducting a clinical trial to evaluate the efficacy and safety of rituximab in patients with lymphocyte-predominant Hodgkin's disease or other CD20-positive subtypes of Hodgkin's disease (where more than 30% of malignant cells expressed CD20) at first or later relapse.[2] Seventeen patients have been treated with intravenous rituximab (375 mg/m² per week * 4 weeks) and updated results of the international, multicenter, phase II trial were reported at the American Society of Hematology 2002 Annual Meeting (ASH abstract 3066).[2] At study entry, 12 patients were diagnosed with LPHD, 3 had CD20+ classic Hodgkin's disease, and 2 patients had Hodgkin's disease transformed to T-cell-rich B-cell lymphoma. The median age of the patients was 40.5 years (range, 18 to 51 years) and the median time from first diagnosis was 9 years (range, 0.5 to 21 years). All patients had at least one prior therapy (median, two prior therapies). Nine patients had stage I or II disease and seven exhibited B symptoms. Response Rate of 88% Data collected by Dr. Schulz and colleagues show that the overall response rate was 88% (15 of 17 evaluable patients, including 10 complete and 5 partial responses). Of the 15 responders, 10 (67%) were in remission after a median follow-up of 12 months, and the median duration of response was 32 months. Two patients exhibited progressive disease. Rituximab treatment was well tolerated. Adverse events were generally transient and infusion related, consisting of fever, chills, rhinitis, and nausea. All were mild to moderate in severity and did not require hospitalization. These results confirm those published by Ekstrand et al.[3] All 22 patients in that phase II trial initially responded to rituximab treatment. Within that 100% overall response were 9 complete responses (41%), 1 unconfirmed complete response (5%), and 12 partial responses (54%). Nine patients (41%), however, subsequently relapsed at a median followup of 13 months. Median progression- free survival was 10.2 months, and adverse events were again minimal. These studies demonstrate that single- agent rituximab is safe and effective in patients with lymphocyte-predominant Hodgkin's disease and other CD20+ Hodgkin's lymphomas, and represents a viable treatment alternative to intensified chemotherapy or radiotherapy in treating this frequently relapsing patient population. Because of the relatively long survival of patients with this subtype of Hodgkin's disease, long-term follow-up of patients treated with rituximab will continue to be of interest.