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.
PHILADELPHIA-In five clinicaltrials involving 250 patients withrelapsed, refractory, or transformedlow-grade non-Hodgkin's lymphoma(NHL), tositumomab and iodine I131 tositumomab (Bexxar) producedresponses of longer duration than didprior chemotherapy. The US Foodand Drug Administration (FDA) OncologicDrugs Advisory Committeerecently recommended that the ra-dioimmunotherapeutic regimen beapproved for the treatment of advancedNHL.The baseline demographics and diseasecharacteristics for patientsenrolled in the five clinical trials aredetailed in Table 1. Reviewing longtermfollow-up of these trials, Mark S.Kaminski, MD, of the University ofMichigan Medical Center in AnnArbor, reported that overall confirmedresponse rate was 56%, and 30% ofpatients achieved a complete response(see Table 2) (ASH abstract 1381).[2-5]The duration of response rangedfrom 10.9 to 45.4 months (median,14.7 months). The median durationof complete response has not yet beenreached, and 70% of patients whoachieved a complete response werealive and still in complete response7.8 years or longer after treatment.Dr. Kaminski concluded that tositumomaband iodine I 131 tositumomabtherapy achieves durable completeresponses in patients with advancedlow-grade NHL.Low-Grade Transformed NHLPatients with NHL have varyingresponse rates to chemotherapy andimmunotherapy depending on thenumber of prior therapies and diseasestage. Other studies examinedresponses to tositumomab and iodineI 131 tositumomab from specificpatient subpopulations.[3-5]Andrew D. Zelenetz, MD, of MemorialSloan-Kettering Cancer Centerin New York, reported responsesfrom patients with transformed low-grade NHL, a subgroup with a particularlypoor prognosis and expectedsurvival of less than 12 months (ASHabstract 1384). Among the 250 patientsenrolled in the five clinical trials,71 patients had a diagnosis oftransformed low-grade NHL.These patients had received a medianof four prior therapies (range, 1to 11). The majority of patients (70%)had bulky disease (tumor size > 5cm); 28% had bone marrow involvement;and approximately half had elevatedlactate dehydrogenase and/ora modified International PrognosticIndex score greater than or equal to 3.The overall confirmed responserate was 39%, and 25% of patientsachieved a complete response. Themedian duration of response was 20months, and the median duration ofcomplete response was 36.5 months.Seventeen patients had a response of12 months or more.
Dr. Zelenetz concluded that theresults demonstrate that tositumomaband iodine I 131 tositumomab "is aneffective therapy for patients withtransformed low-grade NHL."Progression After RituximabAlthough rituximab (Rituxan), achimeric anti-CD20 antibody, is aneffective therapy for indolent NHL,most patients eventually relapse andrequire further treatment. An analysisof 40 patients who failed to respond torituximab or relapsed after treatment,found that tositumomab and iodine I131 tositumomab produced an overallresponse rate of 68% and that 30%of patients achieved a complete response. Sandra J. Horning, MD, ofStanford University Medical Centerin Palo Alto, California, reported thatthe median duration of response was14.7 months, and the median durationof complete response had notbeen reached at the time of the report(ASH abstract 1385). Nine patientswere still in complete response after12 to 26 months of follow-up.These response rates are encouragingconsidering that approximatelytwo-thirds of the patients enrolled inthis study had failed to respond toprior rituximab therapy, Dr. Horningnoted. She concluded that the radioimmunotherapywas "highly effectivein patients with indolent and transformedlymphoma" who have progressedafter rituximab therapy.As Front-Line TreatmentAs with other treatments for NHL,it was expected that response rates totositumomab and iodine I 131 tositumomabwould be greatest in the frontlinesetting. This prompted a study of76 patients with previously untreated,stage III/IV, low-grade (71% follicularsmall cleaved cell, 29% follicularmixed cell) NHL, and poorprognostic factors such as bone marrowinvolvement (63%) and elevatedlactate dehydrogenase (31%).Dr. Kaminski reported that theconfirmed response rate was 95%, and74% of patients achieved a completeresponse. The median duration of responseand the median progressionfreesurvival had not been reachedafter 8 to 66 months of follow-up.The primary toxicities associatedwith treatment included myelosuppressionand hypothyroidism. Grade3 or 4 neutropenia was noted in 34%of patients and grade 3 or 4 thrombocytopeniawas noted in 17% of patients.Dr. Kaminski concluded thatthe regimen achieved a high confirmedcomplete response rate and had anacceptable safety profile in patientswith previously untreated advancedstageNHL.
Leonard JP, Vose J, Younes A:Remission inversion in patients withlow grade and transformed low gradeNHL: duration of response followingtreatment with tositumomab and iodineI 131 tositumomab (Bexxar) reproduciblyexceeds that producedby the preceding therapy (abstract4802). Blood 100:314b-315b, 2002.
Kaminski MS, Zelenetz A, LeonardJ, et al: Bexxar radioimmunotherapyproduces a substantial numberof durable complete responses inpatients with multiply relapsed or refractorylow grade or transformed lowgrade non-Hodgkin’s lymphoma (abstract1382). Blood 100:356a, 2002.
Zelenetz AD, Saleh M, Vose J, etal: Patients with transformed lowgrade lymphoma attain durable responsesfollowing outpatient radioimmunotherapywith tositumomaband iodine I 131 tositumomab (Bexxar)(abstract 1384). Blood 100:357a,2002.
Horning SJ, Younes A, Lucas J,et al: Rituximab treatment failures:tositumomab and iodine I 131 tositumomab(Bexxar) can producemeaningful durable responses (abstract1385). Blood 100:357a, 2002.
Kaminski MS, Tuck M, ReganD, et al: High response rates and durableremissions in patients with previouslyuntreated, advanced-stage,follicular lymphoma treated with tositumomaband iodine I-131 tositumomab(Bexxar) (abstract 1381).Blood 100:356a, 2002.