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Monoclonal gammopathy of ocular significance (MGOS) is a rare subset of monoclonal gammopathy of clinical significance occurring secondary to plasma cell disorders and causing ocular manifestations. We identified 23 patients with paraproteinemic keratopathy (PPK) in the setting of monoclonal gammopathy of unknown significance (MGUS, 10), smoldering multiple myeloma (SMM, 3) or multiple myeloma (MM, 10). Many of these patients with PPK (11/23) presented decreased vision. All patients with MM and 40% of those with other diagnoses such as SMM and MGUS received systemic therapy with or without autologous stem cell transplantation. Four eyes of four patients were treated by penetrating keratoplasty. In most cases, neither ocular nor hematologic treatment afforded a durable improvement in the visual acuity (recurrence after a median of 11 months), despite initial responses. Further studies will be required to determine the optimal strategy to treat and prevent the relapse of ocular symptoms in patients with PPK.

In multiple myeloma, atypical forms with extramedullary involvement exhibit poor survival. The poly-chemotherapeutic regimen D(T)-PACE has shown high activity in relapsed or refractory multiple myeloma. In this large monocentric retrospective study, we addressed the activity of D(T)-PACE-based regimens in 43 heavily pretreated patients with relapsed/refractory multiple myeloma and extramedullary disease.Median age at initiation was 57 years. Four patients had a t(4;14) translocation, 3 had a t(11;14) translocation and 7 had a del(17p). Extramedullary sites were mostly the skin (15 patients), central nervous system (10 patients), and thorax or abdomen (10 patients each). Overall response was achieved in 25 (58%) patients, including 6 (14%) with a complete response. Median progression-free survival was 5.0 months. Median overall survival was 9.0 months. Fourteen patients subsequently underwent stem-cell transplantation. Cytogenetics had no impact on response rate, overall survival and progression-free survival.In the era of several new immunotherapies, D(T)-PACE-based regimens still remain a useful treatment option for a selected group of heavily pretreated myeloma patients.

The Intergroupe Francophone du Myelome 2009 trial (NCT01191060) assessed health-related quality of life (HRQoL) in patients with newly diagnosed multiple myeloma (NDMM) receiving lenalidomide/bortezomib/dexamethasone (RVd) induction therapy followed by consolidation therapy with either autologous stem cell transplantation (ASCT) plus RVd (RVd-ASCT) or RVd-alone; both groups then received lenalidomide maintenance therapy for 1 year. Global HRQoL, physical functioning, and role functioning scores significantly improved for both cohorts from baseline to the end of consolidation and were sustained during maintenance and follow-up, with clinically meaningful changes (RVd-alone: p  = .0002; RVd-ASCT: p  < .001). Similarly, both groups showed clinically meaningful improvements from baseline in fatigue, pain, and disease symptom scores. Side effects of treatment scores remained stable. In the RVd-ASCT group, there was transient worsening in HRQoL immediately after ASCT. These findings suggest that the clinical improvements observed with RVd-based treatment are accompanied by overall improvements in HRQoL for patients with NDMM.

Two hundred and ten nuclear medicine physicians, radiologists, and hematologists from 26 countries attended the 6th International Workshop on Positron Emission Tomography (PET) in Lymphoma and Myeloma held in Menton, France, in September 2016. The meeting was under the auspices of the European Lymphoma Institute (ELI), the European Association of Nuclear Medicine (EANM) the Lymphoma Study Association (LYSA), the Italian Foundation on Lymphoma (FIL) and the Carnot Institute for Lymphoma (CALYM). Forty scientific posters were presented. For the first time, specialists in the field of multiple myeloma (MM) were involved in the expert session. The aim was to establish from the experience of Italian and French studies new guidelines of FDG-PET/CT reporting for myeloma staging and restaging. The meeting dedicated an entire session to MM imaging followed by a session on the role of PET in Peripheral T cell Lymphoma. An entire session addressed the issues of Deauville scale particularly for end treatment assessment and the challenging consequences of immunomodulatory treatments on PET reporting. A specific session presented the potential role of baseline metabolic tumor measurement to predict outcome and identify different risk categories and the main results obtained in different lymphoma entities were described. Whether it could replace clinical staging has been extensively discussed. The more recent results obtained in the H10 trial have been presented and compared to the published data in early stage Hodgkin lymphoma. Finally, the ongoing studies using PET for guiding therapeutic strategies have been reported by the various lymphoma cooperative groups that participated to the meeting.

The European Society for Blood and Marrow Transplantation Chronic Malignancies Working Party held a preceptorship meeting in Turin, Italy on 25-26 September 2014, to discuss the role of stem cell transplantation (SCT) in the treatment of multiple myeloma and other plasma cell disorders. Scientists and clinicians working in the field gathered to discuss a variety of topics including the results of recent clinical trials, basic research, the concept of minimal residual disease, and immune modulation. As individual presentations revealed, important advances have occurred in our understanding of the pathophysiology of myeloma and the role that SCT, along with other forms of immunotherapy, plays in treating it. Each presentation stimulated discussion and exchange of ideas among the attendants. We decided to summarize and, importantly, to update the meeting proceedings in this review to share stimulating discussions and ideas on potentially novel treatment strategies among clinicians.

Whether the efficacy of lenalidomide in the treatment of multiple myeloma (MM) is due to direct tumor toxicity only or to additional immunomodulatory effects is unclear. We studied the effect of lenalidomide treatment on T-cell immune reconstitution in patients with MM who had undergone autologous peripheral blood stem cell transplant (ASCT). Twenty-nine newly diagnosed patients with MM received induction therapy followed by high-dose melphalan and ASCT. After ASCT, 11 patients received lenalidomide consolidation therapy for 2 months followed by maintenance therapy until disease progression. The remaining 18 patients received no treatment. Serial analysis of thymic output, as given by numbers of T-cell receptor excision circles (sjTRECs), and T-cell phenotyping was performed until 18 months post-ASCT. Lenalidomide impaired long-term thymic T-cell reconstitution, decreased CD4 + and CD8 + CD45RA + CCR7 - effector-terminal T-cell absolute counts and increased CD4 + CD25 + CD127 - /low regulatory T-cells. Lenalidomide consolidation and long-term maintenance therapy, administered post-ASCT, may have a potentially negative impact on immune surveillance.

Osteolytic bone lesions are common in patients with multiple myeloma (MM), a clonal plasma cell disorder, and result from increased osteoclastic bone resorption and decreased osteoblastic bone formation. Because mesenchymal stem cells (MSCs) are committed towards cells of the osteoblast lineage, we compared the in vitro characteristics of MSCs from the bone marrow of 18 MM patients (MM-MSCs) and eight normal donors (ND-MSCs). MM-MSCs displayed deficient growth that could be explained in part by the reduced expression of several growth factor receptors on the surface of MM-MSCs compared with ND-MSCs. Receptor downregulation was observed on RT-PCR analysis. A major finding was an approximately fivefold higher expression of osteoblast inhibitor DKK1 at transcript and protein levels in MM-MSCs than ND-MSCs. These data suggest that defective osteoblast function in patients with advanced MM may be related not only to factors released by tumor myeloma cells but also to MSC abnormalities.

This study evaluated the feasibility of using dendritic cells (DCs) to generate, ex vivo, anti-tumor cytotoxic T lymphocytes (CTL) in patients with stage III multiple myeloma (MM). Nucleated cells from eight patients who had received chemotherapy (three of whom had undergone autologous hemopoeitic stem cell transplantation) were collected by apheresis. Their monocytes were enriched using counter-current centrifugation, differentiated into DCs which were further co-cultured with autologous CD8 lymphocytes to induce CTL. The DCs were pulsed either with the idiotypic paraprotein (regarded as a tumor-specific antigen) or with autologous MM cell lysate before co-culture. Specific T-cell responses were measured in IFNgamma enzyme-linked immunospot and chromium release assays of autologous plasmocyte targets. A slight increase in IFNgamma secretion by T-cells was observed for two patients (DCs pulsed with idiotypic paraprotein for one, MM cell lysate for the other). No or weak specific lysis of plasmocyte targets was observed in the chromium release assays. In conclusion, the T-cell response to pulsed DCs was very weak or absent. There are clinical and technical reasons that could explain, in part, this lack of response.

Acute liver failure as an initial manifestation of primary non-Hodgkin's lymphoma is a rare phenomenon with a grim prognosis. We report for the first time on a patient with a history of follicular lymphoma in complete remission, presenting fulminant liver failure due to massive liver infiltration by transformed lymphoma cells and portal vein thrombosis, as an initial manifestation of transformation into large-cell lymphoma.