title: Effect of bendamustine in combination with rituximab on QT interval duration in patients with advanced de novo indolent non-Hodgkin or mantle cell lymphoma.
abstract: OBJECTIVE
  Bendamustine is used in chronic lymphocytic leukemia (first-line) and indolent B-cell non-Hodgkin lymphoma (NHL) that progressed during/within 6 months of treatment with rituximab or a rituximab-containing regimen. This study was a postapproval commitment to investigate bendamustine's effect on cardiac repolarization in treatment-naïve adults with advanced indolent NHL/mantle cell lymphoma (MCL).
  
  
  METHODS
  In this multicenter, open-label, phase 3 study, patients received 6-8 28-day cycles of bendamustine (90 mg/m(2), days 1 and 2) and rituximab (375 mg/m(2), day 1). Exclusions included a history of cardiac conditions with potential for QT prolongation. The primary endpoint was change in Fridericia-corrected QT (QTcF; 3 electrocardiograms per time point) on day 2 of cycle 1, from just before infusion to end of infusion (immediately postinfusion, coinciding with maximum plasma concentration of bendamustine). Change 1 h postinfusion was also measured. Exploratory assessments included specific QTcF outlier analyses (new QTcF >500 ms, change >60 ms) and morphological changes.
  
  
  RESULTS
  Of the 54 enrolled patients (mean age, 62.9 years), 53 received ≥1 dose; 49 completed ≥6 cycles. Mean QTcF change from baseline was 6.7 ms at end of infusion; no mean changes >20 ms were detected ≤1 h postinfusion. No patients met specific outlier criteria at end of infusion or 1 h postinfusion. No morphological changes were detected.
  
  
  CONCLUSIONS
  In this small treatment-naïve population with advanced NHL/MCL, bendamustine did not produce a clinically relevant increase in mean QTcF on the second infusion day. The potential for delayed effects on QT interval after 1 h was not evaluated.
authors.affiliation: Rocky Mountain Cancer Centers, 1700 S. Potomac Street, Aurora, CO, 80012, USA, john.burke@usoncology.com.
authors.forename: John M
authors.initials: JM
authors.lastname: Burke
authors.forename: Richard H C
authors.initials: RH
authors.lastname: van der Jagt
authors.forename: Ian W
authors.initials: IW
authors.lastname: Flinn
authors.forename: Michael D
authors.initials: MD
authors.lastname: Craig
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Joel
authors.initials: J
authors.lastname: Morganroth
authors.forename: Mihaela C
authors.initials: MC
authors.lastname: Munteanu
authors.forename: David A
authors.initials: DA
authors.lastname: MacDonald
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000503:physiopathology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D009588:Nitrogen Mustard Compounds; D000069283:Rituximab; D000069461:Bendamustine Hydrochloride