Lenalidomide is effective for extramedullary disease in relapsed or refractory multiple myeloma

To the Editor: Different therapeutical approaches have been reported for secondary extramedullary plasmacytoma (EP) with poor outcomes. Among the novel antimyeloma agents, whereas thalidomide has demonstrated no efficacy for EP (1–5), bortezomib has demonstrated antitumoral effect in multiple myeloma (MM) relapsing with extramedullary spread (6–10). Some retrospective observations suggest that lenalidomide could be effective in patients with EP (11, 12). Our study reports the role of lenalidomide for EP in daily clinical practice. We analyzed the clinical data of 18 patients not previously reported (eight women), median age 68 yrs (50–87 yrs) with advanced MM and EP treated with lenalidomide-based regimens between October 2007 and July 2010. Investigators were required to report all consecutive patients who fulfilled the following inclusion criteria: (i) to have been treated with lenalidomide-based regimens outside of clinical trials and (ii) to have a clinical follow-up documented at least 3 months after lenalidomide-based treatment was initiated. The study was approved by the Investigational Review Board of Hospital Universitario Doctor Negrı́n, Las Palmas de Gran Canaria, Spain. Patients received a median of three treatment lines (range 1–6), including autologous stem cell transplantation (4 ⁄ 18), bortezomib (18 ⁄18) and thalidomide (3 ⁄ 18). Ten patients (55.5%) had received pretreatment of EP before lenalidomide was given. Twelve patients relapsed after achieving any response to the last therapy and six had refractory disease prior lenalidomide therapy. Three patients had varying degrees of renal failure. A chromosome 13 deletion was observed in four of 12 patients with an available karyotype at diagnosis. Histologic confirmation of the EP was available in 14 patients. Soft tissues surrounding bone lesions were affected in 50% of cases (nine patients) [(skull (n = 2), rib cage (n = 3) and paravertebral (n = 4)]. Subcutaneous plasmacytoma nodules were documented in three patients, and unifocal ⁄multimodal visceral involvement was documented in six patients (liver n = 1), lung and kidney (n = 1), nasopharynx (n = 1), thyroid gland (n = 1), maxillary gland (n = 1) and pleura and mediastinum (n = 1). Lenalidomide was administered orally at an initial dose of 25 mg for 21 consecutive days in repeated 28-d cycles in 14 patients (78%). Four patients (22%) started at 10 mg daily. Median number of lenalidomide cycles administered was 7 (3–21). Table 1 summarizes the treatments and results. Lenalidomide was given in combination with dexamethasone: two patients (11.1%) received high dose of dexamethasone (40 mg ⁄d on days 1–4, 9–12, and 17–22); four patients (22.2%) received intermediate dose of dexamethasone (40 mg ⁄d on days 1–4 and 15–18); nine patients (50%) received 40 mg ⁄d on day 1–4; and in three patients (16.6%), lower dose of dexamethasone was used. Radiotherapy (RT) on involvedfield was delivered in four patients (22.2%). Venous thromboembolism prophylaxis was prescribed in 16 patients (88.8%). Lenalidomide toxicity was found to be comparable with reported in patients with advanced MM treated with lenalidomide containing regimens. Analyses focused on response rates to salvage therapy and survival analysis. Response of MM was assessed according to the International uniform response criteria (13) and the response of EP by measuring size changes by physical examination and ⁄or radiological imaging. Overall response rate of MM was 61.1% (11 patients). Eleven patients (61.1%) showed some response in the EP including complete disappearance in 44.4% (eight patients) and reduction in size in 16.6% (three patients), suggesting that lenalidomide could be active on the tumoral plasma cell, independently if they are located on the bone marrow estromal or in different tissular microenvironment. Of note that all the patients but one that had any serum ⁄urine M-protein decrease showed any reduction in the size of their plasmacytomas. Response rate of EP after lenalidomide in our series was higher than the responses reported with thalidomide (1, 3), similar to previously reported with bortezomib (6–9) and also compares favorably with reported by Alegre et al. (12) in a retrospective study of myeloma patients with EP treated with lenalidomide (OR 61.1% vs. 25%, CR 44.4% vs. 16%). Among responding patients to lenalidomide, three relapsed to therapy during our short follow-up, indicating that new strategies are needed to increase the control of the disease. Overall, the median overall survival and progression-free survival were 14.6 and 9.8 months, respectively. With a median follow-up of 12 months (range, 3–24 months), 10 patients (55.6%) were still alive (three in CR and five in PR) from 5 to 19 months after therapy with lenalidomide. LETTER TO THE EDITOR doi:10.1111/j.1600-0609.2011. 01644.x European Journal of Haematology 87 (281–284)