Maintaining the dose intensity of ICE chemotherapy with a thrombopoietic agent, PEG-rHuMGDF, may confer a survival advantage in relapsed and refractory aggressive non-Hodgkin lymphoma

Introduction: HDT/ASCT is standard for relapsed and refractoryDLCL patients responding to second-line chemotherapy. We incorporateda thrombopoietic agent into the ICE chemotherapy program topotentially: decrease platelet associated toxicities, augmentstem cell collection and maintain dose intensity. Methods: This randomized, double-blind, placebo-controlled phaseI/II trial examines PEG-rHuMGDF versus placebo with ICE chemotherapy.Phase I compared three cohorts and defined a clinically effectivedose (CED). Phase II evaluated the CED versus placebo. Outcomemeasures included safety, hematological end-points, stem cellcollection and the impact of dose-intensity on outcome. Results: Forty-one patients with primary refractory (16) orrelapsed DLCL (25) were treated; Response rates for evaluablepatients are: 75% (12/16) for placebo and 82% (18/22) for PEG-rHuMGDF.PEG-rHuMGDF treated patients had significantly less grade IVthrombocytopenia, higher median platelet nadirs, and less platelettransfusion per cycle. ICE dose intensity was improved withPEG-rHuMGDF versus placebo: 75 versus 42% (P = 0.008). At 8.5years median follow-up, overall and event-free survival are47 and 31%, respectively. Patients treated on PEG-rHuMGDF versusplacebo had improved survival (59 versus 31%, P = 0.06). Conclusion: PEG-rHuMGDF ameliorated thrombocytopenia, improvedplatelet recovery, and maintained ICE dose intensity. Potentialsurvival advantages conferred by maintaining dose intensityrequire validation with newer thrombopoietic agents. Key words: dose-intensity, ICE chemotherapy, non-Hodgkin's lymphoma, refractory, relapsed, transplantation