Cytokine profiles in relapsed multiple myeloma patients undergoing febrile reactions to lenalidomide

Morita, Yasuyoshi; Shimada, Takahiro; Yamaguchi, Tadatoshi; Rai, Shinya; Hirase, Chikara; Emoto, Masakatsu; Serizawa, Kentaro; Taniguchi, Yasuhiro; Ojima, Mayuko; Tatsumi, Yoichi; Ashida, Takashi; Matsumura, Itaru

doi:10.1007/s12185-011-0973-x

Cited by 4 publications

(2 citation statements)

References 5 publications

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“…On the other hand, Morita et al examined serum cytokine levels in 8 relapsed MM patients undergoing febrile reactions to Len and reported that levels of TNF-α and IL-6 were depressed in most cases after the treatment and IL-6 is not always related to CRP levels in MM patients treated with Len. They reported no significant correlation between the clinical response and rate of reduction of serum IL-6 and TNF-α [42]. Although the cytokine release syndrome was absent in our present case, the fact that transient inflammatory reactions may occur in some MM cases treated with Rd might have complicated the evaluation of serum cytokine values.…”

Section: Discussioncontrasting

confidence: 67%

Follow-Up Study of a Multiple Myeloma Patient Successfully Treated with Clarithromycin (CAM), Low-Dose Lenalidomide and Low-Dose Dexamethasone: Significance and Possible Mechanism of Action of CAM as an Add-On Therapy

Takemori¹,

Fukuda²,

Kojima³

2014

CRCM

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Background: Recently, high efficacy of the chemotherapeutic regimen combining clarithromycin (CAM) with lenalidomide (Len) and dexamethasone (Dex) (BiRD) in treating multiple myeloma (MM) patients has been reported. However, the exact mechanism of added CAM has not been fully elucidated. This case report will provide helpful information for understanding the significance and the mechanism of action of CAM as an add-on therapy. Patient: A 78-year-old female patient with IgA-λ type MM was treated with low-dose Len coupled with low-dose Dex (low Rd), and excellent response was achieved for long term, but she later became refractory to this treatment. Then, CAM was added to low Rd (low Rd-CAM, i.e., modified BiRD therapy). This add-on-therapy was found to be effective, but later suspended because of pneumonitis. Then, low-dose Len coupled with CAM (low R-CAM) treatment was applied; but effect of this Dex-free treatment was insufficient. Thus, low Rd-CAM was reapplied and satisfactory reduction of IgA was achieved. This fact suggests that low Rd-CAM is the favorable combination, Dex is requisite and CAM might have enhanced the effect of Dex. In this case, various serum cytokines were examined during the course N. Takemori et al. 675of illness. Only interleukin-6 showed apparent increase, and tumor necrosis factor-α, transforming growth factor-β, soluble-IL-2 receptors and C-reactive protein showed the slight increase during low Rd-CAM treatment. The results seem somewhat conflicting, but it seems that intricate cytokine response due to immune activation might have occurred during low Rd-CAM treatment.

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Section: Discussioncontrasting

confidence: 67%

Follow-Up Study of a Multiple Myeloma Patient Successfully Treated with Clarithromycin (CAM), Low-Dose Lenalidomide and Low-Dose Dexamethasone: Significance and Possible Mechanism of Action of CAM as an Add-On Therapy

Takemori¹,

Fukuda²,

Kojima³

2014

CRCM

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“…The fever resolved spontaneously after stopping lenalidomide [7]. Tumor flares have been reported after using lenalidomide for the treatment of chronic lymphocytic leukemia [8], and this might be another mechanism of lenalidomide induced fever, however the exact mechanism remains unclear [9]. The management of these febrile reactions consists of holding the medication until resolution of the symptoms; patient can be re-challenged at a lower dose followed by escalation as tolerated.…”

Section: Discussionmentioning

confidence: 99%

Can lenalidomide be accused to induce high grade pattern of fever in a multiple myeloma patient? A Question to be answered

Gohary¹,

Nahedh²,

Fakih³

2019

J Stem Cell Res Med

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Lenalidomide is a second-generation immunomodulatory agent and a potent analogue of thalidomide that is FDA approved mainly for the treatment of multiple myeloma (MM) and transfusion-dependent anaemia due to low or intermediate-1-risk myelodysplastic syndromes (MDS) associated with 5q deletion among other indications. Through its action on the immune system, lenalidomide alters the production of different cytokines ultimately resulting in immune activation against tumours. This immune activation may lead to collateral immune toxicities like fever, angioedema, Stevens-Johnson syndrome, tumour flare and others. Here we report a case of lenalidomide-induced high grade fever in a patient with MM and we summarize the literature about the physiology of such reaction and how to mitigate this adverse event.

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Association of Th1 and Th2 cytokines with transient inflammatory reaction during lenalidomide plus dexamethasone therapy in multiple myeloma

et al. 2013

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Transient inflammatory reactions have been reported in a subpopulation of patients with multiple myeloma (MM) during lenalidomide (Len) plus dexamethasone (DEX) therapy. Here, we examined serum levels of Th1 (IL-2 and IFN-γ) and Th2 cytokines (IL-6 and TNF-α) in nine refractory or relapsed MM patients treated with Len plus low-dose DEX. Six patients showed elevation of C-reactive protein (CRP) after the initiation of therapy. In these patients, IFN-γ and IL-6 were also elevated in two and three patients, respectively. The remaining three patients showed no appreciable changes in CRP or these cytokines. Furthermore, Len enhanced the production of both Th1 and Th2 cytokines in normal peripheral blood mononuclear cells and in patient bone marrow mononuclear cells containing primary myeloma cells and lymphocytes. These results suggest that the modulation of the Th1 and Th2 cytokine production by Len may contribute to transient inflammatory reaction in MM patients.

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Cytokine profiles in relapsed multiple myeloma patients undergoing febrile reactions to lenalidomide

Cited by 4 publications

References 5 publications

Follow-Up Study of a Multiple Myeloma Patient Successfully Treated with Clarithromycin (CAM), Low-Dose Lenalidomide and Low-Dose Dexamethasone: Significance and Possible Mechanism of Action of CAM as an Add-On Therapy

Follow-Up Study of a Multiple Myeloma Patient Successfully Treated with Clarithromycin (CAM), Low-Dose Lenalidomide and Low-Dose Dexamethasone: Significance and Possible Mechanism of Action of CAM as an Add-On Therapy

Can lenalidomide be accused to induce high grade pattern of fever in a multiple myeloma patient? A Question to be answered

Association of Th1 and Th2 cytokines with transient inflammatory reaction during lenalidomide plus dexamethasone therapy in multiple myeloma

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