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

PURPOSE:

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: John M Burke, Richard H C van der Jagt, Ian W Flinn, Michael D Craig, Ling Chen, Joel Morganroth, Mihaela C Munteanu, David A MacDonald
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 76 Issue 1 Pg. 211-6 (Jul 2015) ISSN: 1432-0843 [Electronic] Germany
• PMID: 26006703 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Nitrogen Mustard Compounds
• Rituximab
• Bendamustine Hydrochloride

Topics

• Antibodies, Monoclonal, Murine-Derived (administration & dosage, pharmacology)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• Bendamustine Hydrochloride
• Electrocardiography (drug effects)
• Female
• Heart Rate (drug effects)
• Humans
• Lymphoma, Mantle-Cell (drug therapy, physiopathology)
• Lymphoma, Non-Hodgkin (drug therapy, physiopathology)
• Male
• Middle Aged
• Nitrogen Mustard Compounds (administration & dosage, pharmacology)
• Rituximab