Journal
BRITISH JOURNAL OF HAEMATOLOGY
Volume 159, Issue 2, Pages 154-163Publisher
WILEY
DOI: 10.1111/bjh.12008
Keywords
lenalidomide; mantle cell lymphoma; NK cells; T cells; regulatory T cells
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Funding
- Celgene Corporation
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We present data from a phase II study investigating a novel treatment strategy for relapsed/refractory mantle cell lymphoma (MCL). Twenty-six patients received lenalidomide 25 mg/d (days 121 of a 28-d cycle) for up to 6 cycles followed by low-dose maintenance lenalidomide (15 mg) in responding patients. Eight patients achieved complete or partial response to give an overall response rate of 31% with median response duration of 22.2 months [95% confidence interval (CI) 0.053.6] and median progression-free survival (PFS) of 3.9 months (95% CI 0.011.1). An additional six patients (23%) achieved stable disease. Eleven patients received maintenance with median PFS of 14.6 months (95% CI 7.321.9). Correlative studies showed that peripheral T and Natural Killer (NK) cells increased in responding patients by 4060% over the first 6 cycles with an initial dip in NK cells suggestive of tumour infiltration. Peripheral regulatory T cells were increased in MCL patients (P = 0.001) and expanded further following lenalidomide. Sequential plasma analysis showed increased IL12 p40 and IL7 alongside decreased MMP9, IL10, and adiponectin. Finally, a significant correlation (P = 0.02) between gender and response suggested that female MCL patients were more sensitive to lenalidomide than males. In summary, we confirm the activity, safety and immunomodulatory properties of lenalidomide in MCL and highlight its potential as a low-dose maintenance agent.
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