Long-term efficacy and safety of sirolimus therapy in patients with lymphangioleiomyomatosis

Abstract

Background Sirolimus has been confirmed to be effective for lymphangioleiomyomatosis (LAM), a rare multisystem neoplastic disease in women. The long-term effects of sirolimus treatment for LAM, however, are largely unknown. We aimed to analyze the long-term efficacy and safety of sirolimus therapy for LAM with 4-year follow-up. Methods In total, 142 sporadic LAM patients who took sirolimus for 1–4 years were retrospectively enrolled for this analysis. The variables used for analysis included pulmonary function tests, arterial blood gas analysis, 6-min walking distance (6MWD), St. George’s Respiratory Questionnaires (SGRQ) and serum vascular endothelial growth factor-D (VEGF-D) levels before and after the initiation of sirolimus therapy. The rates of change (slope) in those variables were calculated, and adverse events were also analyzed. Results In total, 122, 83, 60 and 32 patients out of 142 were followed for 1, 2, 3 and 4 years respectively. Sirolimus treatment improved the change rate in forced expiratory volume in 1 second (FEV 1 ) and forced vital capacity (FVC) compared with the data before treatment (FEV 1 , − 10 ± 15 vs. − 178 ± 36 ml/y, P < 0.001 and FVC, 54 ± 22 vs.-72 ± 68 ml/y, P < 0.05). In comparison to the baseline measurements, significant improvements were observed in FEV 1 at the first year; FVC at 1–2 years; arterial oxygen levels, 6MWD, and SGRQ at 1–3 years; and VEGF-D at 1–4 years. Overall, all variables stabilized or improved during the 4 years of observation. Adverse events related to sirolimus were mild. Conclusion Sirolimus therapy is effective at improving or stabilizing pulmonary function, oxygen levels, exercise capacity, and quality of life in patients with LAM for up to 4 years. VEGF-D is maintained at a lower level for 4 years after treatment. Adverse events related to sirolimus were mild.

Individual approach for treatment of primary intestinal lymphangiectasia in children: single-center experience and review of the literature

“…The drug effect was seen after 4 weeks of use, like in our cases. However, the appropriate drug discontinuation time is debatable because there is no current consensus or guidelines [ 40 , 41 ]. Incidence of many adverse effects of sirolimus is dose related, and a frequent adverse effect of sirolimus, which is up to 40%, is elevation of creatinine level.…”

Individual Approach for Treatment of Primary Intestinal Lymphangiectasia in Children: Single-center Experience and Review of the Literature

“…The drug effect was seen after four weeks of use, like in our cases. However, the appropriate drug discontinuation time is debatable because there is no current consensus or guidelines [40,41]. Incidence of many adverse effects of sirolimus is dose related, and a frequent adverse effect of sirolimus, which is up to 40%, is elevation of creatinine level.…”

Lymphangioleiomyomatosis: A Case Report and Review of Clinical Features and Management

“…Pharmacologically, LAM patients can be treated with sirolimus, an immunosuppressant that targets mTOR and interrupts T-cell activation downstream of the interleukin-2 (IL-2) receptor. This treatment modality has had success in stabilizing pulmonary function in patients with LAM, as well as improving oxygenation to the lungs, exercise capability, and quality of life [14,16]. With therapeutic serum levels of sirolimus and medication compliance, this immune modulator can prevent further pneumothorax incidents [14].…”