Phase I–II study of lenalidomide and alemtuzumab i

Authors: Maria Winqvist Fariba Mozaffari Marzia Palma Sandra Eketorp Sylvan Lotta Hansson Håkan Mellstedt Anders Österborg Jeanette Lundin

Publish Date: 2016/11/04

Volume: 66, Issue: 1, Pages: 91-102

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Abstract

This phase I–II study explored safety immunomodulatory and clinical effects of lenalidomide weeks 1–16 and alemtuzumab weeks 5–16 in 23 patients with refractory chronic lymphocytic leukemia Most patients had Rai stage III/IV disease and were heavily pretreated median 4 prior therapies and 61 had del17p/del11q Eleven of 19 evaluable patients 58 responded with a median response duration of 12 months 1–29+ time to progression was short in nonresponders Lenalidomide had a narrow therapeutic dose range 25 mg/day was not efficient and maximum tolerated dose was 5 mg/day Grade 3–4 neutropenia and thrombocytopenia occurred in 84 and 55 30 had febrile neutropenia and CMVreactivation requiring valganciclovir occurred in 30 of patients The frequency of proliferating Ki67+ CD8+ T cells was increased at week 4 with further increase in both the CD4+ and CD8+ subsets p  001 and 005 which was accompanied by significant upregulation of HLADR after addition of alemtuzumab Antigenexperienced cells increased at week 4 as the frequency of effector memory cells increased in the CD8+ subset p  0003 while effector cells decreased in both the CD8+ and CD4+ subsets p  00001 and p  001 The Th1/Th2 balance was unchanged at week 4 but shifted toward a Th2 profile after combination therapy At end of treatment the frequency of Th17 and regulatory T cells was reduced p  001 naïve T cells decreased and effector memory T cells increased p  005 and p  001 Granzyme B+ T cells increased at 30week followup p  005 PD1 expression was unaffected In conclusion lowdose lenalidomide and alemtuzumab induced major perturbations of T cells including increased proliferative activity and cytotoxic potential

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