High incidence of diarrhea in patients on long term therapy with lenalidomide and dexamethasone for multiple myeloma

Abstract

8586 Background: Several phase II and III trials have demonstrated high response rates and improved survival and excellent tolerability with lenalidomide (Len) and dexamethasone (Len-Dex) in newly diagnosed myeloma (NMM). Therefore many pts continue on therapy for prolonged periods which might be associated with unexpected side effects. Methods: We reviewed the frequency of diarrhea with Lenalidomide in NMM, on two trials utilizing Len-Dex at MAyo. and in MM009/MM010 phase III trials. Toxicity data was prospectively collected using NCI CTCAE v 3.0. Results: Sixty seven NMM pts in Mayo trials and 703 pts in MM 009/010 trials were studied. In Mayo trials, the median duration of follow up and therapy was 28.6 mos and 8.5 mos (range, 1–47 mos) respectively. Eighteen pts (27%) reported diarrhea.Median duration of therapy for patients with diarrhea was 31 mos (range, 9–43) compared to 5 mos (range, 1–47) without diarrhea; (P < 0.001). No diarrhea was observed with therapy < 8 mos. Median time to diarrhea onset was 19 mos. One pt had grade 3 persistent diarrhea; all others had grade 1 or 2. One pt with grade 2 diarrhea required dose reduction of Len and one with grade 3 diarrhea required treatment cessation for palliation. Others benefitted from a conservative approach with Imodium as needed. We analyzed MM009/010 trials to estimate baseline diarrhea risk and risk with Len addition. The incidence of diarrhea was 38.8% and 28% in the Len-Dex (n=353) and Dex arm (n=350) respectively( excess risk of 10%). Multivariate logistic regression was done including therapy duration and treatment arm. Only duration of therapy was significant in this analysis (P<0.001); treatment with Len-Dex was not significant (P=0.4).We examined a cohort of pts in MM009/010 trials receiving 9–15 mos of therapy to further understand the effect of treatment duration. With adjustment for treatment duration, the incidence of diarrhea was identical; 42.3% (Len-Dex) and 42.5% (placebo-Dex). Discussion: We report diarrhea as an unexpected side effect in a significant proportion of patients with prolonged Len-Dex combination therapy. Most of the risk can be attributed to long-term Dex therapy. Most patients respond to conservative treatments with spontaneous resolution at treatment cessation. No significant financial relationships to disclose.