Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma

Davies, Faith E.; Raje, Noopur; Hideshima, Teru; Lentzsch, Suzanne; Young, Gloria; Tai, Yu Tzu; Lin, Boris K.; Podar, Klaus; Gupta, Deepak; Chauhan, Dharminder; Treon, Steven P.; Richardson, Paul G.; Schlossman, Robert; Morgan, Gareth J.; Muller, George W.; Stirling, David I.; Anderson, Kenneth C.

doi:10.1182/blood.v98.1.210

Cited by 846 publications

(618 citation statements)

References 17 publications

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“…[13][14][15] Nevertheless, these studies were not powered to IMiDs. 28 The toxicities with lenalidomide-prednisone and lenalidomide maintenance were comparable. Nine percent of patients required lenalidomide dose-reduction in the lenalidomide-prednisone arm versus 22% in the lenalidomide arm (p=0.004).…”

Section: Discussionmentioning

confidence: 82%

Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial

Gay

Oliva

Petrucci

et al. 2015

The Lancet Oncology

287

252

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AperTO -Archivio Istituzionale Open Access dell'Università di TorinoChemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: A randomised, multicentre, phase 3 trial / Gay, Francesca; Oliva, Stefania; Petrucci, Maria Teresa; Conticello, Concetta; Catalano, Lucio; Corradini, Paolo; Siniscalchi, Agostina; Magarotto, Valeria; Pour, Ludk; Carella, Angelo; Malfitano, Alessandra; Petrò, Daniela; Evangelista, Andrea; Spada, Stefano; Pescosta, Norbert; Omedè, Paola; Campbell, Philip; Liberati, Anna Marina; Offidani, Massimo; Ria, Roberto; Pulini, Stefano; Patriarca, Francesca; Hajek, Roman; Spencer, Andrew; Boccadoro, Mario; Palumbo, Antonio. -In: LANCET ONCOLOGY. -ISSN 1470-ISSN -2045-ISSN . -16:16(2015, pp. 1617-1629. Original Citation:Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: A randomised, multicentre, phase 3 trial This is an author version of the contribution published on:Questa è la versione dell'autore dell'opera: [Lancet Oncol. 2015 Dec;16(16):1617-29. doi: 10.1016/S1470-2045 Background. High-dose melphalan plus autologous stem-cell transplantation (MEL200-

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Section: Discussionmentioning

confidence: 82%

Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial

Gay

Oliva

Petrucci

et al. 2015

The Lancet Oncology

287

252

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“…This confirms previous observations of activation of NK and T cells after therapy with thalidomide or lenalidomide. 14,15 This immunostimulating effect of lenalidomide might be an important mechanism of its anti-myeloma activity beside its anti-angiogenetic properties and its apoptotic effect. The increase of T-regulatory cells in myeloma patients remains unclear, 16 and after allo-SCT, Tregulatory cells seem to have a GVHD-protecting effect.…”

Section: Discussionmentioning

confidence: 99%

Lenalidomide as salvage therapy after allo-SCT for multiple myeloma is effective and leads to an increase of activated NK (NKp44+) and T (HLA-DR+) cells

Lioznov

El-Cheikh

Hoffmann

et al. 2009

Bone Marrow Transplant

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We investigated efficacy and toxicity of lenalidomide in 24 heavily pretreated myeloma patients with a median age of 59 years (range: 37-70) and relapse after allo-SCT. Lenalidomide was given at a dose of 15 mg (n ¼ 4), or 25 mg (n ¼ 20), orally once daily on day 1 to day 1 every 28 days, with (n ¼ 20) or without (n ¼ 4) DHAP. The median number of lenalidomide cycles was five (range: 2-17). Major side effects were leukopenia (grade 4: 4%, grade 3: 21% and grade 2: 17%) and thrombocytopenia (grade 3: 17% and grade 2: 29%); infectious complications were observed in 50%. Non-hematological toxicity consisted of muscle cramps (n ¼ 9), fatigue (n ¼ 5) and constipation (n ¼ 2). Mild grade I-II GVHD was seen in three patients. Response was achieved in 66%: CR in 8%, VGPR in 8%, PR in 50% and SD in 13%. The median time to progression was 9.7 months (95% confidence interval (CI): 7.5-11.9), and median OS was 19.9 months (95% CI: 17.3-22.5). Immunomonitoring after lenalidomide showed significant increase of activated NK (NKp44 þ ) and T (HLA-DR þ ) cells, as well as regulatory T cells (CD4 þ , CD25 þ , CD127 lo ), supporting an immunomodulating anti-myeloma effect of lenalidomide.

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“…It also increases production of the antiinflammatory cytokine IL-10 by LPS-stimulated PBMC and consequently inhibits the expression, but not the enzymatic activity, of cyclooxygenase-2 (20). Lenalidomide induces T-cell proliferation and IL-2 and interferon (IFN)-c production (19,21) and it augments cytotoxic activity of natural killer cells (22).…”

Section: Pharmaco Dynami C Pr Oper Tiesmentioning

confidence: 99%

Lenalidomide in the treatment of multiple myeloma: a review

2008

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Lenalidomide is an immunomodulatory drug derived from thalidomide. It was developed to maximize the anti-inflammatory and anti-neoplasic properties of thalidomide and to reduce its toxicity. The molecular mechanism of action of lenalidomide is unclear, but its therapeutic activity is mainly due to its well defined antiinflammatory, immunomodulatory, anti-proliferative and anti-angiogenic properties. In relapsed or refractory multiple myeloma (MM), lenalidomide, combined with standard dose dexamethasone, is superior to dexamethasone alone in terms of time to progression, response rate and overall survival. The most commonly reported adverse events include haematological toxicity with manageable neutropenia and thrombopenia. Lenalidomide does not trigger the limiting toxicities of thalidomide: somnolence, neuropathy and constipation. Lenalidomide, in combination with dexamethasone, is indicated for the treatment of MM patients who have received at least one prior therapy and is administered orally at the dose of 25 mg q.d. for 21 days of 28-day cycles. The drug is being investigated for the treatment of newly diagnosed MM. In this review, we summarize the pharmacokinetic, pharmacodynamic and clinical trial data on lenalidomide.

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Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma

Cited by 846 publications

References 17 publications

Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial

Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial

Lenalidomide as salvage therapy after allo-SCT for multiple myeloma is effective and leads to an increase of activated NK (NKp44+) and T (HLA-DR+) cells

Lenalidomide in the treatment of multiple myeloma: a review

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