The clinical utility of lenalidomide in multiple myeloma and myelodysplastic syndromes

Bonkowski, Joseph; Vermeulen, Lee C.; Kolesar, Jill

doi:10.1177/1078155209351967

Cited by 15 publications

(11 citation statements)

References 14 publications

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“…With the simplest of regimens (ie, lenalidomide plus dexamethasone), the annual cost of therapy is approximately $100 000 USD, not including the extra monitoring required for patients on active therapy and management of adverse events. 68,69 Part of the "cost" of overtreatment may include increased side effects, which may translate into inferior quality of life. Finally, long-term safety data for protracted lenalidomide use are limited.…”

Section: Consensus Recommendations On Treatmentmentioning

confidence: 99%

Smoldering multiple myeloma requiring treatment: time for a new definition?

Dispenzieri

Stewart

Chanan‐Khan

et al. 2013

Blood

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Smoldering multiple myeloma (SMM) bridges the gap between monoclonal gammopathy of undetermined significance (a mostly premalignant disorder) and active multiple myeloma (MM). Until recently, no interventional study in patients with SMM showed improved overall survival (OS) with therapy as compared with observation. A report from the PETHEMA-GEM (Programa Español de Tratamientos en Hematologica) group described both fewer myeloma-related events and better OS among patients with high-risk SMM who were treated with lenalidomide and dexamethasone. This unique study prompted us to review current knowledge about SMM and address the following questions: (1) Are there patients currently defined as SMM who should be treated routinely? (2) Should the definitions of SMM and MM be reconsidered? (3) Has the time come when not treating is more dangerous than treating? (4) Could unintended medical harm result from overzealous intervention? Our conclusion is that those patients with the highest-risk SMM (extreme bone marrow plasmacytosis, extremely abnormal serum immunoglobulin free light chain ratio, and multiple bone lesions detected only by modern imaging) should be reclassified as active MM so that they can receive MM-appropriate therapy and the paradigm of careful observation for patients with SMM can be preserved.

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Section: Consensus Recommendations On Treatmentmentioning

confidence: 99%

Smoldering multiple myeloma requiring treatment: time for a new definition?

Dispenzieri

Stewart

Chanan‐Khan

et al. 2013

Blood

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“…As this drug may produce peripheral neuropathy it is important to monitor its effects and avoid prolonged use for more than one year (46). Interestingly, the less toxic derivative of thalidomide, lenalidomide, seems to induce itch (47).…”

Section: Diagnostics and Treatmentmentioning

confidence: 99%

Paraneoplastic Itch: An Expert Position Statement from the Special Interest Group (SIG) of the International Forum on the Study of Itch (IFSI)

Weißhaar¹,

Weiß²,

Mettang³

et al. 2015

Acta Derm Venerol

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In clinical practice, the term "paraneoplastic itch" is used to describe itch in patients with cancer. Patients with hematological or solid tumor malignancies can be affected. In general, paraneoplastic itch is considered a rare disorder. However, paraneoplastic itch in hematological malignancies such as polycythemia vera and lymphoma are relatively frequent while other forms of paraneoplastic itch are in fact extremely rare. The true frequency of this symptom is unclear, epidemiological data in this field are limited. Itch in malignant disease may additionally impair patients' quality of life. A population-based cohort study showed that chronic itch without concomitant skin changes is a risk factor for having undiagnosed hematologic and bile duct malignancies. Paraneoplastic itch is rather resistant to treatment. In 2012, an interdisciplinary interest group of physicians and researchers was founded, aiming to generate a clear definition of paraneoplastic itch. In this paper we briefly review the current knowledge and aim to define what can be summarized under the term "paraneoplastic itch".

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“…Lenalidomide is FDA approved for treatment of multiple myeloma, mantle cell lymphoma, and myelodysplastic syndrome. In multiple myeloma, lenalidomide has direct cytotoxic effects against the tumor cells (6, 7), presumably through the increased targeting and degradation of the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) by the Cul4–Rbx1–DDB1–Cereblon E3 ubiquitin ligase complex (8–10). …”

Section: Introductionmentioning

confidence: 99%

Lenalidomide Induces Interleukin-21 Production by T Cells and Enhances IL21-Mediated Cytotoxicity in Chronic Lymphocytic Leukemia B Cells

Browning

Byrd

Gupta

et al. 2016

Cancer Immunology Research

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The immunomodulatory drug lenalidomide has demonstrated efficacy in chronic lymphocytic leukemia (CLL) patients, despite a lack of direct cytotoxic effect in vitro. The mechanism of lenalidomide efficacy in vivo is thought to occur via a combination of enhanced immune activity and an alteration of tumor cell–microenvironment interactions. We demonstrate in whole blood from CLL patients that lenalidomide significantly depletes malignant B cells. Lenalidomide also induced production of interleukin-21 (IL21) and its mRNA in T cells from CLL patients. Lenalidomide also enhanced upregulation of functional IL21 receptor (IL21R) on the cell surface and increased receptor mRNA in vitro. The in vitro combination of IL21 and lenalidomide enhanced IL21-mediated cytotoxicity toward CLL cells through a variety of mechanisms. We show association of cell death with upregulation of Bid by IL21, enhanced upregulation of Bid by the combination therapy, and diminished Lck and downstream BCR signaling activation of Syk and PLCG2. Collectively, we demonstrated an immune cell–tumor cell interaction through lenalidomide-mediated induction of IL21 and IL21R, with enhanced IL21-mediated cytotoxicity, which provides justification for this combination in clinical trials for CLL patients.

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The clinical utility of lenalidomide in multiple myeloma and myelodysplastic syndromes

Abstract: lenalidomide is an effective agent for the treatment of MDS with a 5q deletion and relapsed or refractory multiple myeloma.

Cited by 15 publications

References 14 publications

Smoldering multiple myeloma requiring treatment: time for a new definition?

Smoldering multiple myeloma requiring treatment: time for a new definition?

Paraneoplastic Itch: An Expert Position Statement from the Special Interest Group (SIG) of the International Forum on the Study of Itch (IFSI)

Lenalidomide Induces Interleukin-21 Production by T Cells and Enhances IL21-Mediated Cytotoxicity in Chronic Lymphocytic Leukemia B Cells

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