Lenalidomide Administration In Patients With POEMS Syndrome

The most effective treatment for patients with POEMS is high dose therapy with autologous stem cell support (ASCT); however, several patients are not be eligible for this procedure while others may relapse after ASCT. Hence, there is a clear need for the development of new therapies for the management of POEMS. Lenalidomide is an immunomodulatory drug that has proven efficacy in patients with multiple myeloma and seems to represent an attractive option for use in POEMS. The purpose of this study was to synthesize all available data emerging from case reports/case series and our experience so as to evaluate the efficacy and safety of lenalidomide in patients with POEMS.

This systematic review was performed in accordance with the PRISMA guidelines. Eligible articles were identified by a search in MEDLINE and ClinicalTrials.gov databases for the period up to April 8, 2013. The search strategy included the following keywords: (POEMS AND (lenalidomide OR revlimid). In addition, we checked all the references of eligible articles, so as to identify potentially eligible papers. Articles in Chinese and Japanese were excluded; two investigators, working independently, searched the literature and extracted data from eligible studies. All studies that examined the efficacy and safety of lenalidomide administration in patients with POEMS diagnosis, regardless of sample size, were considered eligible. Moreover, eligible cases of patients diagnosed with POEMS syndrome and who were treated with lenalidomide in our Department were additionally included in this pooled analysis. POEMS diagnosis was established according to criteria by Dispenzieri et al (Am J Hematol 2012). Hematological, radiological and neurological response was assessed according to the statements of the authors in the individual eligible manuscripts; in case these were not clearly stated, we applied the D'Souza criteria.

An overall of 11 articles, which included 51 patients, were analyzed. The mean age of patients at lenalidomide administration was 55.2 years (SD: 10.8; median: 54.5 years; range: 32-79 years). The mean time from POEMS diagnosis to lenalidomide administration was 30.1 months (SD: 37.4; median: 18 months; range: 0- 164 months). In most patients lenalidomide was administered at a dose of 25 mg (days 1-21) in combination with dexamethasone (40 mg weekly in cycles of 28 days), until disease progression or unacceptable toxicity. Lenalidomide was given as first, second, third and fourth line treatment in 19.1%, 50%, 19.1% and 11.9% of patients, respectively. The mean time from last treatment till lenalidomide administration was 17.2 months (SD: 27.0; median: 5 months; range: 0-111 months). There were 43 patients evaluated for hematological response; the latter included complete response in 18.6%, very good partial response in 39.5%, partial response in 37.2% and stabilization of the disease in 4.7% of cases. Of note, VEGF reduction occurred in all reported cases; neuropathy improved in 92.0% of cases and stabilized in 8%. Organomegaly was improved in 87% of cases, skin changes in 73.7% and edema in 95%. In 8 patients, ASCT was performed after lenalidomide treatment and no particular toxicity or harvest issues were observed. Lenalidomide was well tolerated; two cases with respiratory infection grade 3 and one case neutropenia grade 4 were recorded. Data to assess progression were available in 44 patients; among them 6 progressed. Of note, among the 6 patients who progressed during the observation period, only two relapsed within the first year. The Kaplan-Meier PFS estimate at 12 months was equal to 93.9%. No deaths were reported during the follow-up period. Given the small sample size as well as the small number of events, no significant associations emerged. Nevertheless, some trends of marginal significance seem worth observing, i.e. longer time interval between diagnosis and lenalidomide administration was associated with less frequent neuropathy response (OR: 0.98, 95% CI: 0.96-1.00, p=0.053).

We conclude that the use of lenalidomide in patients with POEMS seems to be a highly effective and safe therapy, even in patients previously exposed to one or more lines of therapy. The PFS achieved by lenalidomide was rather prolonged (PFS at 12 months 93.9%); furthermore, marked clinical, neurological, hematological and VEGF levels improvement in patients treated with this agent was observed.