Impact of prior bortezomib therapy on the incidence of lenalidomide-induced skin rash in multiple myeloma: A propensity score-matched multi-institutional cohort study

Dote, Satoshi; Ito, Kaori; Itakura, Shoji; Yasu, Takeo; Hira, Daiki; Noda, Shinichi; Yamada, Shuichi; Kobayashi, Yuka; Takato, Tsuyoshi

doi:10.1093/annonc/mdy286.020

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“…In support of our study, there are many reports showing cases of eosinophilia during LEN treatment, 73,74 and the incidence of eosinophilia after LEN administration is higher in patients with rashes. 72 Our results showed IMiD-treated DCs enhanced the Th2 polarization of memory Th2 cells but not naïve T cells; therefore, administration of IMiDs might induce atopic-like rash by exacerbating existing Th2 memory cells rather than inducing the differentiation of Th2 cells from naive T cells.…”

Section: Discussionmentioning

confidence: 56%

“…This is similar to a meta-analysis of 10 trials showing rashes in 27.2% of cases 71 and a report of 144 MM patients receiving LEN therapy in a 4-institutional cohort study with 35% of cases developing rashes. 72 These observations suggest IMiDs polarize the immune response toward the allergic axis by promoting mDC activation and upregulating CCL17 expression. The development of atopy-like rashes following LEN treatment is likely a result of Th2-mediated immunostimulation.…”

Section: Discussionmentioning

confidence: 96%

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Immunomodulatory drugs suppress Th1-inducing ability of dendritic cells but enhance Th2-mediated allergic responses

et al. 2020

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Immunomodulatory drugs (IMiDs), lenalidomide and pomalidomide, are widely used treatments for multiple myeloma; however, they occasionally lead to episodes of itchy skin and rashes. Here, we analyzed the effects of IMiDs on human myeloid dendritic cells (mDCs) as major regulators of Th1 or Th2 responses and the role they play in allergy. We found that lenalidomide and pomalidomide used at clinical concentrations did not affect the survival or CD86 and OX40-ligand expression of blood mDCs in response to lipopolysaccharide (LPS) and thymic stromal lymphopoietin (TSLP) stimulation. Both lenalidomide and pomalidomide dose-dependently inhibited interleukin-12 (IL-12) and TNF production and STAT4 expression, and enhanced IL-10 production in response to LPS. When stimulated with TSLP, both IMiDs significantly enhanced CCL17 production and STAT6 and IRF4 expression and promoted memory Th2-cell responses. In 46 myeloma patients, serum CCL17 levels at the onset of lenalidomide-associated rash were significantly higher than those without rashes during lenalidomide treatment and those before treatment. Furthermore, serum CCL17 levels in patients who achieved a very good partial response (VGPR) were significantly higher compared with a less than VGPR during lenalidomide treatment. The median time to next treatment was significantly longer in lenalidomide-treated patients with rashes than those without. Collectively, IMiDs suppressed the Th1-inducing capacity of DCs, instead promoting a Th2 response. Thus, the lenalidomide-associated rashes might be a result of an allergic response driven by Th2-axis activation. Our findings suggest clinical efficacy and rashes as a side effect of IMiDs are inextricably linked through immunostimulation.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 96%