Background To investigate the utility of regular serum VEGF (sVEGF) levels assessment in the monitoring of POEMS syndrome. Methods We retrospectively reviewed data of 30 patients with POEMS syndrome whose sVEGF was tested regularly every 6 months. sVEGF levels after treatment were measured and correlated with disability (Overall Neuropathy Limitations Scale, ONLS), clinical impairment (measured with the modified Clinical Response Evaluation Scale, mCRES), and relapse-free survival. The ability of sVEGF to predict disease flares during remission and refractory disease was also analysed. Results Patients with normalised serum VEGF levels (< 1000 pg/ml) at 6 months showed prolonged relapse-free survival (at 3-year 94% for complete VEGF response, 57% partial, 0% none, p < 0.001) and greater later clinical improvement (median ΔmCRES complete VEGF response -5 vs partial -4, p = 0.019, and vs no VEGF response -2, p = 0.006). After remission, the sensitivity of 6-month sVEGF monitoring in predicting clinical relapse was 58% with a specificity of 100%. In patients refractory to treatment, the sensitivity in predicting further clinical worsening was 15%. In addition, in 25% of the patients in remission and 16% of those refractory to therapy, sVEGF levels only increased at the time of relapse. Conclusions Regular sVEGF assessment is a valid biomarker in the prediction of disease reactivation in POEMS syndrome and was particularly useful during the phase of remission.

SummaryBortezomib‐ and lenalidomide‐containing regimens are well‐established therapies in multiple myeloma (MM). However, despite their extensive use, head‐to‐head comparisons have never been performed. Therefore, we compared bortezomib and lenalidomide in fixed‐duration therapies. In this open‐label, phase III study, we randomized MM patients at first relapse to receive either nine cycles of bortezomib plus cyclophosphamide plus dexamethasone (VCD) or lenalidomide plus cyclophosphamide plus dexamethasone (RCD). The primary endpoint was achievement of a very good partial response (VGPR) or better at six weeks after nine treatment cycles. From March 2011 to February 2015, 155 patients were randomized. VGPR or better was achieved by 12 patients (15%) in the VCD arm and 14 patients (18%) in the RCD arm (P = 0·70). Median progression‐free survival (PFS) was 16·3 (95% CI: 12·1–22·4) with VCD and 18·6 months (95% CI: 14·7–25·5) with RCD, and the two‐year overall survival (OS) was 75% (95% CI: 66–86%) and 74% (95% CI: 64–85%) respectively. In subgroup analyses, no differences in PFS were observed in bortezomib‐ and lenalidomide‐naïve patients, nor in patients who received a bortezomib‐based regimen in first line. Adverse events were consistent with the well‐established safety profiles of both drugs. Bortezomib and lenalidomide treatments were equally effective in terms of depth of response, PFS, and OS in MM patients at first relapse.

Autologous peripheral blood stem cell transplantation should be considered first-line therapy in young patients with POEMS. The best protocol to collect peripheral blood stem cells remains to be defined, because of the disease rarity and the heterogeneity of published case series. We collected clinical and laboratory data from 25 patients undergoing mobilization, of whom 11 were mobilized using cyclophosphamide (CY) followed by granulocyte colony-stimulating factor (G-CSF) and 14 patients using G-CSF. The incidence of poor mobilization was low and not statistically different between the 2 groups. Both schemes (CY plus G-CSF versus G-CSF alone) were able to harvest a sufficient CD34+ cell dose.

Introduction. POEMS syndrome is a rare paraneoplastic condition associated to an underlying plasmacellular dyscrasia. The use of alkylating agents and autologous peripheral blood stem cell transplantation (aPBSCT) seem to be the best strategy.

Because of the rarity of the disease, randomized clinical trials for multicentric Castleman disease (MCD) remain a challenge and, as a consequence, there is no established standard of care. Siltuximab is a chimeric immunoglobulin G1 monoclonal antibody against human IL-6 which was recently approved by FDA. Eligible patients in Italy were granted early access through a Named Patient Program (NPP). The aim of this observational multicenter retrospective study was to analyze outcomes and toxicity data of relapsed or refractory MCD patients treated with siltuximab in a real life context. All the 9 patients who received siltuximab in Italy under the NPP were enrolled. Median duration of treatment was 285days (range, 104-1113days). The global overall response rate was 33.3%. At the time of this analysis, none of the 3 responder patients had subsequently disease relapse: response duration was 20, 23, and 37months, respectively. Grade 1 to 2 fatigue and pruritus were observed in 2 (22.2%) patients, and weight gain was reported in only 1 patient (grade 1); local edema was reported in 2 patients with a grade 2 presentation. The most common side effect was upper respiratory tract infection reported in 3 (33.3%) patients but in these cases was grades 1 to 2. No patient developed an infusion-related reaction. Our NPP data support siltuximab as single agent in the real-life experience of the treatment of relapse/refractory MCD patients in effectiveness, safety profile, and sustained disease control.

POEMS syndrome is a rare multisystem disease characterised by polyneuropathy (P), organomegaly (O), endocrinopathy (E), monoclonal gammopathy (M) and skin changes (S).1 A usually severe demyelinating and axonal neuropathy is often the most prominent and disabling clinical manifestation.2 The pathogenesis of POEMS syndrome is unclear even if overproduction of vascular endothelial growth factor (VEGF) seems to play a major role.1 2 Autologous haematopoietic stem cell transplantation (HSCT) is now considered the most effective therapy in patients with disseminated disease.1 This therapy is however not feasible in all patients because of their advanced age or the presence of severe concomitant conditions. A number of immune or cytostatic agents have been also used with variable efficacy in POEMS syndrome,1 including lenalidomide whose efficacy we recently reported in 13 of the 18 treated patients.3 Little is known however on the degree of response to lenalidomide in comparison with HSCT. We retrospectively reviewed the clinical, biological and electrophysiological data from 15 patients with POEMS syndrome diagnosed according the criteria proposed by Dispenzieri,1 who neurologically improved after therapy with lenalidomide or HSCT. All the patients had been treated and followed at our institution for at least 2 years. The study was approved by the institutional review board of our institute, and all the patients signed an informed consent for the review of their data. Six patients (four males, two females; mean age at disease onset 48 years, range …

Purpose of review Several advances have been made on the pathogenesis and therapy of neuropathies associated with paraproteinemia (monoclonal gammopathy). It is important for the neurologist to understand the pathogenetic relevance of this association especially when the hematological disease does not require per se any therapy. Recent findings Treatment of the neuropathy in patients with malignant paraproteinemia is mainly addressed by the hematologist while the neurologist is mainly involved in the initial diagnosis and in deciding whether the neuropathy is caused by the disease or by the chemotherapy used for the disease. There is little evidence that the neuropathy is caused by the hematological condition in patients with IgG or IgA monoclonal gammopathy of undetermined significance (MGUS) unless there is an evidence of a reactivity of the paraprotein with nerve or evidence of its presence in the nerve. Patients with a chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)-like presentation should be treated as CIDP while there is no evidence that immune or chemotherapy may be effective in the other patients. In most patients with IgM paraproteinemia, that is usually a MGUS or an indolent Waldenström's macroglobulinemia, the neuropathy is induced by an immune reactivity of the paraprotein with nerve and particularly with the myelin-associated glycoprotein. There are now consistent data also from controlled studies that the anti-CD20 monoclonal antibody rituximab may improve the neuropathy in these patients. POEMS syndrome is a severe condition characterized by a disabling neuropathy whose prognosis has improved in the last few years with therapies against the proliferating plasma cell clone or vascular endothelial growth factor including local radiotherapy and chemotherapy followed by autologous stem cell transplantation. Other therapies are also available for patients not eligible or resistant to transplantation, including lenalidomide and possibly thalidomide or bortezomib. Summary Several new therapies are now available for patients with paraproteinemic neuropathy consistently improving the prognosis of these neuropathies. In most instances, however, their efficacy needs to be confirmed in controlled trials.

We report the long-term clinical outcomes of a retrospective multicenter study that enrolled 169 patients with multiple myeloma (MM) in first relapse after failing autologous stem cell transplantation (SCT). After HLA typing at relapse, 79 patients with a suitable donor, 72 (91%) of whom eventually underwent salvage allogeneic SCT (allo-SCT), were compared with 90 patients without a donor who were treated with multiple lines of salvage treatment with bortezomib and/or immunomodulatory agents. At a median follow-up of 30 months (range, 2-180 months) for all patients and 110 months (range, 38-180 months) for surviving patients, 7-year progression-free survival (PFS) was 18% in the donor group and 0% in the no-donor group (hazard ratio [HR], 2.495; 95% confidence interval [CI], 1.770-3.517; P < .0001). Seven-year overall survival (OS) was 31% in the donor group and 9% in the no-donor group (HR, 1.835; 95% CI, 1.306-2.577; P < .0001). By multivariate analysis, chemosensitivity to salvage treatments and presence of a suitable donor were significantly associated with better PFS and OS. The long-term follow-up of this study confirms the significant PFS benefit and provides new evidence of an OS advantage for patients with MM who have a suitable donor and undergo allo-SCT. Allo-SCT should be considered as a treatment option in young relapsed patients with high-risk disease features after first-line treatment.

POEMS syndrome is a rare, chronic and disabling condition. The causes of this condition remain unknown; however, chronic overproduction of pro-inflammatory cytokines appears to be a major contributor. Early diagnosis is essential to start treatment before the clinical condition of the patient becomes compromised.A complete evaluation of the disease at its onset is essential for treatment decision. In localized disease, curative doses of radiation (50 Gy) is the recommended therapy. On the other hand, patients with disseminated disease should be given systemic therapy. Treatment-related morbidity can be minimized by an effective induction therapy that modifies the cytokine status, improving clinical condition and control disease severity before mobilization and transplantation. Patients not suitable for hematopoietic stem cell transplantation (HSCT) are usually treated with alkylator-based therapy. Novel agents may also offer benefits to patients with a poor performance status or renal dysfunction, and induce transplantation eligibility. Given the biological characteristics of POEMS, immunomodulatory effects and the absence of neurotoxicity, lenalidomide appears to be an effective therapy for the treatment of POEMS, both as short induction therapy before PBSCT and in non-transplant eligible patients, as it showed high response rate and long lasting responses.At present, however, guidelines for the diagnosis and treatment of POEMS are not available and appear advocated. Keywords: POEMS, plasma cell dyscrasia; Osteosclerosis; neuropathy

Given its anti-angiogenic activity, lenalidomide may have a role in the treatment of POEMS (Peripheral neuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cell disorder and Skin changes) syndrome. This prospective, open-label, pilot study evaluated the combination of lenalidomide + dexamethasone (RD) in 18 POEMS syndrome patients (13 pre-treated, 5 newly-diagnosed but ineligible for high-dose therapy). Treatment consisted of six cycles of lenalidomide (25 mg/day for 21 days followed by 7 days rest) plus dexamethasone (40 mg/once a week). Patients responding after six cycles continued treatment until progression or unbearable toxicity. The primary endpoint was the proportion of patients with either neurological or clinical improvement. The RD combination was considered as deserving further evaluation if 9 of the first 15 patients responded. Ten responses were observed among the first 15 enrolled patients, meeting the primary endpoint. Fifteen of 18 patients (83%) completed six RD cycles: 13 (72%) patients responded and nine had both clinical and neurological improvement. Among the 15 patients who completed the six RD cycles, four were still on treatment after a 25-month follow-up. At 39 months of follow-up, all patients were alive with a 3-year progression-free survival of 59%. No patient discontinued RD for toxicity. Overall, the RD regimen showed a high incidence of prolonged symptoms improvement and was well tolerated in most POEMS patients.

Bortezomib (Bort) and lenalidomide (Len) are standard treatments for relapsed MM. So far there has never been a formal head to head comparison between them. We designed a multicentric, open label, phase III study aiming to compare Bort and Len. This is the first planned analysis of efficacy.

Bendamustine is an old bi-functional alkylating agent which, thanks to its extended efficacy and good tolerability, is living a second youth with growing use in several lympho-proliferative maligna...