A Highly Effective and Practical Corticosteroid Regimen to Overcome Skin Rash Associated with Immunomodulatory Drugs Allowing Reinstitution of Therapy

Introduction Immunomodulatory drugs (IMiDs) are backbone of myeloma therapy in induction and maintenance therapy after transplant for patients (pts) with Multiple Myeloma (MM). The incidence of IMiD-associated rash is up to 27% (Nardone, et al, Clinical Lymphoma Myeloma and Leukemia. 2013) and importantly heralds a favorable prognosis (Kojima, et al. Blood. 2016) suggesting more robust immune stimulation by this class of drugs; however, lack of optimal management strategy of this toxicity can deprive large subset of pts from maintenance therapy after transplant and lead to potential detrimental impact on survivals. The concurrent weekly dexamethasone (Dex) does not diminish the incidence of skin eruptions with IMiDs (Sviggum, et al. Archives of dermatology. 2006), therefore we designed a low dose daily and tapering corticosteroid regimen to tame this immune response upon restarting IMiDs and allow desensitization and reinstitution of the same IMiD which may not be achieved by standard weekly Dex. Here, we present our experience with this regimen. Methods In this retrospective study, pts with MM treated with lenalidomide and pomalidomide were reviewed for any IMiD-associated dermatologic toxicity. We followed the same corticosteroid regimen for all IMiD-related rash in our clinic without changing Dex dosing. Result A total of 160 pts were evaluated. The incidence of rash was found to be 13% (n=21). IMiDs were instituted as part of induction regimen in 71% (n=15) and as maintenance therapy after transplant in 29% (n=6) of pts. Median time to development of rash after IMiD initiation was 28 days (range, 2-232). The rashes were characterized as morbilliform in 86% (n=18), urticaria in 9.5% (n=2) and blisters in 5% (n=1) of pts. Pruritis or pain was associated with 86% of rashes (n=15). According to NCI-CTCAE, rashes were graded as low (I-II) in 89% (n=17) and high (III-IV) in 19% of pts. All pts were managed by temporary treatment interruption and upon clearance of rash, re-institution of the same IMiD concomitantly with a standardized 3-week steroid rash prophylaxis protocol (prednisone at 10 mg daily for 10 days, followed by 5 mg daily for 10 days, followed by 5 mg on alternate days for 10 days). As a result, all pts were able to restart the same IMiD either at same (n=5, 24%) or reduced (n=16, 76%) dose with none re-experiencing any dermatologic adverse effect afterward. There was no association between rash development and changes in creatinine clearance (p=0.42). Median eosinophil count at rash development was observed to be significantly higher as compared to eosinophil count at IMiD initiation (380 × 106 vs 130 × 106 respectively, p=0.01). Conclusion The proposed 3-week corticosteroid regimen showed 100% success rate in terms of reinstituting IMiDs, therefore it may provide a highly effective and practical short term immunosuppression required to enable pts to restart IMiDs.