6533b7d1fe1ef96bd125d7d1
RESEARCH PRODUCT
Associations of ofatumumab exposure and treatment outcomes in patients with untreated CLL receiving chemoimmunotherapy
Nancy GoldsteinIra GuptaStephan StilgenbauerLei FangMichele GorczycaFrancisco J. Hernandez-ilizaliturriSteen LisbyThomas J. KippsJiří MayerJan DürigRoxanne C. JewellWilliam G. WierdaLukas SmolejSwaminathan Padmanabhan-iyerGeorg HessLaimonas Griskeviciussubject
OncologyMaleCancer ResearchLymphomaDrug ResistanceMedizinKaplan-Meier EstimatePharmacologychemistry.chemical_compound0302 clinical medicineAntineoplastic Agents ImmunologicalRecurrencehemic and lymphatic diseasesAntineoplastic Combined Chemotherapy Protocols80 and overChronicNeoplasm MetastasisLenalidomideCancerAged 80 and overUnivariate analysisLeukemiaRemission InductionAntibodies MonoclonalHematologyphase IIMiddle AgedLymphocyticThalidomideFludarabineClinical trialTreatment OutcomeOncologyTolerability6.1 Pharmaceuticals030220 oncology & carcinogenesisRetreatmentMathematikRituximabFemalePatient SafetyRefractory Chronic Lymphocytic LeukemiaUntreated Chronic Lymphocytic Leukemiamedicine.drugAdultmedicine.medical_specialtyCyclophosphamidelenalidomideClinical Trials and Supportive ActivitiesClinical SciencesImmunologyCmaxAntineoplastic AgentsNeutropeniaOfatumumabAntibodies Monoclonal HumanizedDrug Administration ScheduleArticle03 medical and health sciencesRare DiseasesClinical ResearchChemoimmunotherapyInternal medicinemedicineImmunologic FactorsAnimalsHumansIn patientAdverse effectLenalidomideAgedNeoplasm StagingChromosome Aberrationsbusiness.industryB-CellEvaluation of treatments and therapeutic interventionsmedicine.diseaseHaresLeukemia Lymphocytic Chronic B-CellDiscontinuationClinical trialchemistryDrug Resistance NeoplasmNeoplasmbusinessCLL030215 immunologydescription
Relationships between patient characteristics, ofatumumab pharmacokinetics, and treatment outcomes were investigated in this phase 2 trial of ofatumumab plus fludarabine and cyclophosphamide (FC) in untreated chronic lymphocytic leukemia. Patients were randomized 1:1 to receive 500 or 1000 mg ofatumumab (Cycle 1; 300 mg) plus FC every 4 weeks for six cycles. Median C(max) and C(trough) values were similar at Cycle 1 regardless of the ultimate clinical outcome. At later doses, these values were higher for patients with complete response (CR) than for other patients. Higher C(max) and C(trough) values at Cycles 3 and 6 were significantly associated with an increased likelihood of CR, whereas ofatumumab pharmacokinetics were not associated with an objective response (OR) on the basis of univariate analyses. Multivariate analyses indicated that baseline patient/disease factors were predominantly associated with CR (17p status) or OR (bulky lymphadenopathy, gender, and serum thymidine kinase), rather than ofatumumab pharmacokinetics. Trial registration: www.clinicaltrials.gov (NCT00410163).
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-07-07 |