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 formof Hodgkin's disease characterized bythe absence of classic Reed-Sternbergcells and the accumulation of large,malignant, mononuclear cells, knownas lymphocytic and/or histiocytic cells,in peripheral lymph nodes. These cellsare of B-cell lineage and, uniqueamong the other Hodgkin's diseasesubtypes, express CD20 but do notexpress CD15 and CD30.[1] BecauseLPHD comprises only about 5% of allcases of Hodgkin's disease, LPHDspecifictherapies have not been developedand LPHD patients enrolledin clinical trials tend to be groupedwithin larger studies of classic formsof Hodgkin's disease.In general, LPHD has the mostfavorable prognosis of all Hodgkin'sdisease subtypes. The clinical courseof this lymphocyte-predominantHodgkin's disease tends to be indolent,and patients often respond wellinitially to therapy. Complete responserates have been reported to range from89% to 96% with chemotherapy-basedtreatment regimens.[1] Relapses arecommon, however, with approximately13% to 36% of patients relapsingwithin a median follow-up ofapproximately 6 to 7 years.[1]The toxicity associated with radiotherapyor chemotherapy can becomesignificant with repeated treatmentsupon relapse. According to investiga-tors the use of a B-cell-depleting, anti-CD20 monoclonal antibody such asrituximab (Rituxan) may be efficaciousin this indication.Rituximab After RelapseHolger Schulz, MD, and colleagueswith the German Hodgkin's LymphomaStudy Group are conducting aclinical trial to evaluate the efficacyand safety of rituximab in patientswith lymphocyte-predominantHodgkin's disease or other CD20-positivesubtypes of Hodgkin's disease(where more than 30% of malignantcells expressed CD20) at first or laterrelapse.[2] Seventeen patients havebeen treated with intravenous rituximab(375 mg/m² per week * 4 weeks)and updated results of the international,multicenter, phase II trial werereported at the American Society ofHematology 2002 Annual Meeting(ASH abstract 3066).[2]At study entry, 12 patients werediagnosed with LPHD, 3 had CD20+classic Hodgkin's disease, and 2 patientshad Hodgkin's disease transformedto T-cell-rich B-cell lymphoma.The median age of the patientswas 40.5 years (range, 18 to 51 years)and the median time from first diagnosiswas 9 years (range, 0.5 to 21years). All patients had at least oneprior therapy (median, two prior therapies).Nine patients had stage I or IIdisease and seven exhibited B symptoms.Response Rate of 88%Data collected by Dr. Schulz andcolleagues show that the overall responserate was 88% (15 of 17 evaluablepatients, including 10 completeand 5 partial responses). Of the 15responders, 10 (67%) were in remissionafter a median follow-up of 12months, and the median duration ofresponse was 32 months. Two patientsexhibited progressive disease.Rituximab treatment was well tolerated.Adverse events were generallytransient and infusion related, consistingof fever, chills, rhinitis, andnausea. All were mild to moderate inseverity and did not require hospitalization.These results confirm those publishedby Ekstrand et al.[3] All 22patients in that phase II trial initiallyresponded to rituximab treatment.Within that 100% overall responsewere 9 complete responses (41%), 1unconfirmed complete response(5%), and 12 partial responses (54%).Nine patients (41%), however, subsequentlyrelapsed at a median followupof 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 effectivein patients with lymphocyte-predominantHodgkin's disease and otherCD20+ Hodgkin's lymphomas, andrepresents a viable treatment alternativeto intensified chemotherapy orradiotherapy in treating this frequentlyrelapsing patient population. Becauseof the relatively long survival ofpatients with this subtype of Hodgkin'sdisease, long-term follow-up of patientstreated with rituximab will continueto be of interest.

References:

1.

Ekstrand BC, Horning SJ. Lymphocytepredominant Hodgkin’s disease.Curr Oncol Rep 4:424-433, 2002.

2.

Schulz H, Rehwald U, Reiser M,et al: Phase-II trial of rituximab inpatients with relapsed CD20-positiveHodgkin’s lymphoma: an update fromthe German Hodgkin’s LymphomaStudy Group (GHSG) (abstract 3066).Blood 100:775a, 2002.

3.

Ekstrand BC, Lucas JB, HorwitzSM, et al: Rituximab in lymphocytepredominant Hodgkin’s disease:results of a phase II trial. Blood 100(Feb 13): 2003.