Phase 1 investigation of lenalidomide/rituximab plus outcomes of lenalidomide maintenance in relapsed CNS lymphoma

著者: James L. Rubenstein, Huimin Geng, Eleanor J. Fraser, Paul Formaker, Lingjing Chen, Jigyasa Sharma, Phoebe Killea, Kaylee Choi, Jenny Ventura, John Kurhanewicz, Clifford A. Lowell, Jimmy J. Hwang, Patrick Treseler, Penny K. Sneed, Jing Li, Xiaomin Wang, Nianhang Chen, Jon A. Gangoiti, Pamela N. Münster, Bertil Damato - Blood Advances 2018 被引用: 193

CNS lymphoma. Nine subjects with relapsed, refractory CNS lymphoma achieved better than partial response with lenalidomide monotherapy, 6 maintained response ≥9 months, and 4 maintained response ≥18 months. Median progression-free survival for lenalidomide/rituximab was 6 months. In the independent cohort, response duration with lenalidomide maintenance after complete responses 2 through 5 were significantly longer than response durations after standard therapy. The CSF/plasma partition coefficient of lenalidomide was ≥20% at 15- and 20-mg dose levels. Change in CSF interleukin-10 at 1 month correlated with clinical response and response duration to lenalidomide. Metabolomic profiling of CSF identified novel biomarkers, including lactate, and implicated indoleamine-2,3 dioxygenase activity with CNS lymphoma progression on lenalidomide. We conclude that lenalidomide penetrates ventricular CSF and is active as monotherapy in relapsed CNS lymphomas. We provide evidence that maintenance lenalidomide potentiates response duration after salvage in relapsed PCNSL and delays whole brain radiotherapy (WBRT). This trial was registered at www.clinicaltrials.gov as #NCT01542918.