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A phase I study of lenalidomide in combination with fludarabine and rituximab in previously untreated CLL/SLL

Leukemia volume 24, pages 1972–1975 (2010)Cite this article

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Lenalidomide is an immunomodulatory drug related to thalidomide that has recently been reported to have significant single-agent activity in relapsed chronic lymphocytic leukemia (CLL), with response rates of 35–50% including some complete responses.1, 2 The mechanism of action is unknown, but appears to be immune-mediated given that lenalidomide alters cytokine levels and stimulates T- and natural killer-cell function and lacks cytotoxicity against CLL in vitro.3 In CLL patients, the administration of lenalidomide can be associated with tumor flare, a syndrome of painful enlarging lymphadenopathy, increased white count, fever and rash.1, 2 This tumor flare can potentially escalate to become life-threatening, with renal insufficiency, tumor lysis or a systemic inflammatory response.4, 5 The mechanism of tumor flare remains unknown.

Given the high reported response rates with lenalidomide and its theoretical potential to help preserve immune function, we undertook this phase I study of lenalidomide in combination with fludarabine rituximab to determine the maximum tolerated dose of lenalidomide in combination with fludarabine rituximab, as well as to assess any preliminary signs of efficacy. This prospective study enrolled patients with previously untreated CLL/small lymphocytic lymphoma who required therapy based on the 1996 NCI WG criteria. Adequate organ function was required and was defined as ANC >1000/μl, platelets >50 000/μl, creatinine ⩽1.5 mg/dl and total bilirubin ⩽1.5 mg/dl. All patients tested negative for hepatitis B and C, and none had autoimmune hemolytic anemia. The study was approved by the Dana-Farber Harvard Cancer Center Institutional Review Board, and all patients signed informed consent before the initiation of the therapy.

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Acknowledgements

This work was supported in part by NIH Grant K23 CA115682 to JRB. ASF is supported in part by NIH Grants 2P01CA092625 and CA-103244. We are indebted to the patients who participated in this study and the clinic staff who supported our research sample collection. We also appreciate the assistance of the CLL Research Consortium Tissue Core, which provided IGVH and ZAP70 results for these patients.

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Authors and Affiliations

  1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    J R Brown, E Mikler, V Dalton, H Reynolds, C Thompson, S M McDonough, J Ritz & A S Freedman

  2. Department of Medicine, Harvard Medical School, Boston, MA, USA

    J R Brown, J Abramson, E Hochberg, J Ritz & A S Freedman

  3. Division of Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

    J Abramson & E Hochberg

  4. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA

    L Werner & D Neuberg

  5. Center for Clinical and Translational Research, Dana-Farber Cancer Institute, Boston, MA, USA

    Y Kuang

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  1. J R Brown
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  2. J Abramson
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  3. E Hochberg
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  4. E Mikler
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  5. V Dalton
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  6. L Werner
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  11. J Ritz
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  12. D Neuberg
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  13. A S Freedman
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Corresponding author

Correspondence to J R Brown.

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Competing interests

This study was investigator-initiated but received per patient funding and free lenalidomide from Celgene. JR Brown has served as a consultant for Celgene.

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Brown, J., Abramson, J., Hochberg, E. et al. A phase I study of lenalidomide in combination with fludarabine and rituximab in previously untreated CLL/SLL. Leukemia 24, 1972–1975 (2010). https://doi.org/10.1038/leu.2010.199

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