Multiple Myeloma Patients with Lenalidomide-Associated Skin Rash Have a Favorable Prognosis

Abstract

Background: Lenalidomide, one of the immunomodulatory drugs, is an important component of treatment for multiple myeloma. Lenalidomide inhibits the proliferation of tumor cells via antiangiogenesis, induces apoptosis and acts directly on the immune system and tumor microenvironment. Immunomodulatory effects of lenalidomide notably stimulate the production of cytokines and activation of T-cells and natural killer cells. Skin rash is a frequent adverse event of lenalidomide. Some studies have shown a correlation between the efficacy of anti-cancer agents such as tyrosine kinase inhibitors and the development of skin rash. However, the relationship between the development of lenalidomide-associated skin rash and its efficacy is unclear. We conducted a retrospective survey to clarify whether development of skin rash correlates with the efficacy of lenalidomide. Materials and Methods: All patients with multiple myeloma who received lenalidomide at 9 hospitals in Japan from July 2009 to December 2015 were serially registered. The chart review was performed for all identified patients to obtain the following information; age, sex, performance status at the initiation of lenalidomide, International Staging System (ISS) classification, prior chemotherapy regimen, tumor response, development of skin rash and clinical outcomes. A log-rank test was used to assess the relationship between the presence of skin rash and survival. A two-sided p < 0.05 was considered statistically significant. This study received approval from the appropriate ethics committees. Results: We identified 215 patients (92 women and 123 men), with a median age was 69 years (range, 39-86 years). Types of myeloma were as follows: 139 patients of IgG, 43 of IgA, and 29 of Bence-Jones protein. ISS was available for 204 patients, and of these, 63, 73, and 68 patients were classified as ISS stage I, II, and III, respectively. The median number of prior therapies was 2 (range, 0-6); 161 (74.9%) and 46 patients (21.4%) had previously received bortezomib and thalidomide, respectively. Fifty patients (23.3%) had undergone previous autologous stem cell transplantation. Sixty-five patients (30.2%) developed a skin rash after lenalidomide initiation, and the median time to onset of skin rash was 12 days. The patients with and without skin rash were similar with respect to age, type of myeloma, and ISS. The median follow-up of survivors was 28.9 months (range, 1.7-80.3 months). The progression-free survival and overall survival were better in patients who had skin rash than in those who did not (p = 0.009 and p = 0.033, respectively) (Figures A and B). Conclusions: In this study, the progression-free survival and overall survival among patients with skin rash during lenalidomide therapy was significantly superior to the patients without skin rash. Lenalidomide-associeated skin rash in patients with multiple myeloma may be a predictive factor of their clinical outcome. Figure Figure. Disclosures Nagai: Takeda: Honoraria, Research Funding; Janssen: Research Funding; Mundipharma KK: Research Funding.

Skin rash after immunomodulatory drugs for plasma cell neoplasms: effective practical corticosteroid desensitisation regimen

“…Whether development of rash correlates with improved outcomes is currently not known. A retrospective study showed significantly superior PFS and OS in 65 patients who developed lenalidomide induced skin rash 2. However, in our study, outcomes were similar in both cohorts.…”

“…Immunomodulatory drugs (IMiDs) are the backbone of myeloma therapy for patients with plasma cell neoplasm (PCN) 1. Therapy is often complicated by development of dermatologic adverse effects associated with IMiDs and may herald a favourable prognosis suggesting a more robust immune stimulation by this class of drugs 2. The incidence of IMiD-associated rash is up to 27% in some reports impeding maximal benefit.…”

Elevated eosinophil level predicted long time to next treatment in relapsed or refractory myeloma patients treated with lenalidomide

“…In contrast, in MM‐025 trial, a phase 2 trial for LD in Japanese patients with NDMM, the incidence of any grade of skin rash was 61.5%, and the incidence of grades 3 to 4 of skin rash was 15.4% . Kojima et al reported that skin rash was a predictor for long‐term progression free survival and OS in patients with MM who underwent treatment with lenalidomide; in their retrospective study, the incidence of any grade skin rash was 30.2%, which suggests that the incidence of skin rash may be higher in Japanese patients with myeloma who undergo treatment with lenalidomide. Nevertheless, those authors did not report an association between the skin rash and elevated eosinophils.…”

Efficacy and Safety of Lenalidomide Prednisolone Combination Treatment for Japanese Elderly Multiple Myeloma Patients

“…But we did not find a significance difference through our analysis. 9 This is believed to be due to the high number of patients that stopped treatment because of rash. It may be important to continue Len by making some adjustments in rash management.…”