This special supplement to Oncology NewsInternational includes updated results ofstudies with anti-CD20 therapy and othertargeted therapies in the treatment oflymphomas, chronic lymphocytic leukemia,and immune thrombocytopenic purpura. Theresults were presented at the American Societyof Hematology 44th Annual Meeting inPhiladelphia, December 6 to 10, 2002.
DUARTE, California-Radioimmunotherapyprovides a uniqueopportunity to deliver systemic radiotherapyconcurrently with immunotherapy,offering efficacy comparablewith that of total body irradiationwhile reducing the toxicity. The ibritumomabtiuxetan (Zevalin) regimenis a radioimmunotherapeutic treatmentthat employs rituximab (Rituxan)in addition to indium-111 radiolabeledibritumomab tiuxetan(111In-ibritumomab tiuxetan), andyttrium-90 radiolabeled ibritumomabtiuxetan (90Y-ibritumomab tiuxetan).Because the therapeutic dose ofradiation is targeted to a specific celltype (ie, CD20+ B cells), it reduces apatient's risk for toxicities associatedwith total body irradiation.A phase I/II trial tested this highdoseregimen in combination withhigh-dose etoposide and cyclophosphamide(Cytoxan, Neosar), followedby autologous stem cell transplantation,in patients with poor-risk orrelapsed B-cell non-Hodgkin's lymphoma(NHL). Auayporn Nademanee,MD, of City of Hope NationalMedical Center in Duarte, California,presented data showing that the additionof a high-dose ibritumomab tiuxetan-rituximab regimen to high-doseetoposide and cyclophosphamidedoes not increase transplant-relatedtoxicity and does not delay engraftment(ASH abstract 679).
Countdown to TransplantTwenty-six patients were enrolledand 18 patients were treated. Patientand disease characteristics are summarizedin Table 1.On day -21 before autologous stemcell transplantation, patients weretreated with an intravenous infusionof 250 mg/m2 rituximab to clear peripheralB cells and improve ibritumomabtiuxetan biodistribution, followedby dosimetry with 5 mCi111In-ibritumomab tiuxetan. Oneweek later, patients received 40 to 100mCi 90Y-ibritumomab tiuxetan toobtain a target dose of no greater than1,000 cGy to normal organs, combinedwith 5 mCi of 111In-ibritumomabtiuxetan.High-dose etoposide (40 to 60 mg/kg) was administered 4 days beforetransplant and high-dose cyclophosphamide(100 mg/kg), 2 days beforetransplant.Stem cells were reinfused when theradiation dose to the reinfused stemcells was estimated to be less than5 cGy. The median delivered dose of90Y-ibritumomab tiuxetan was 74.9mCi (range, 33.6 to 105 mCi).Treatment Well ToleratedThe treatment was well tolerated.Mucositis, neutropenic fever, and rashwere the most common acute toxicities.There were no transplant-relateddeaths.All patients achieved engraftment.The median time to reach an absoluteneutrophil count above 500/μL was10 days (range, 8 to 17 days) and themedian time to reach a platelet countabove 20,000/μL was 18 days (range,12 to 123 days). These median timesare similar to those reported for patientswith high-risk, persistent, orrelapsed NHL who received mobilizedperipheral blood stem cell orautologous bone marrow transplants.All seven patients with active diseaseat stem cell transplantationachieved complete remission. Seventeenof 18 treated patients were aliveand in remission after a median follow-up of 8 months (range, 1 to 24months). In addition, the 1-year estimatedoverall survival and diseasefreesurvival were both 92%.This preliminary study suggeststhat this novel treatment regimen maybe effective in heavily pretreated patientswith refractory NHL who areeligible to receive stem cell transplantation.
Nademanee A, Molina A, FormanSJ, et al: A phase I/II trial of highdoseradioimmunotherapy (RIT) withZevalin in combination with highdoseetoposide (VP-16) and cyclophosphamide(CY) followed by autologousstem cell transplant (ASCT)in patients with poor-risk or relapsedB-cell non-Hodgkin’s lymphoma(NHL) (abstract 679). Blood 100:182a,2002.
Vose JM, Sharp G, Chan WC, etal: Autologous transplantation for aggressivenon-Hodgkin’s lymphoma:results of a randomized trial evaluatinggraft source and minimal residualdisease. J Clin Oncol 20:2344-2352,2002.