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Eltrombopag (ELT), an oral thrombopoietin receptor agonist, has recently emerged as a promising new drug for the treatment of aplastic anemia (AA). How ELT is used outside of clinical trials in the real-world setting and results of this treatment are not known. We conducted therefore a retrospective survey on the use of ELT in AA among EBMT member centers. We analyzed the 134 patients reported in our survey together with 46 patients recently published by Lengline et al. The median follow-up from start of ELT treatment was 15.3 months, with 85.6% patients alive at last follow-up. Importantly, only 28.9% of our patients received ELT according to the FDA/EMA label as monotherapy in the relapsed/refractory setting, whereas 16.7% received ELT upfront. The overall response rate in our cohort was 62%, very similar to the results of the pivotal ELT trial. In multivariate analysis, combination therapy with ELT/cyclosporine/ATG and response to previous therapy were associated with response. Overall survival was favorable with a 1-year survival from ELT start of 87.4%. We identified age, AA severity before ELT start and response to ELT as variables significantly associated with OS. Two patients transformed to MDS; other adverse events were mostly benign. In sum, ELT is used widely in Europe to treat AA patients, mostly in the relapsed/refractory setting. Response to ELT is similar to the clinical trial data across different age groups, treatment lines, and treatment combinations and results in favorable survival. [ABSTRACT FROM AUTHOR]

Background: T cell-replete haploidentical stem cell transplantation (haplo-SCT) is a valid therapeutic option for adult patients with high-risk acute myeloid leukemia (AML) lacking an HLA-matched sibling or unrelated donor.Method: We retrospectively analyzed the outcomes of 912 AML patients ≥45 years of age who had undergone haplo-SCT with either myeloablative conditioning (MAC; n = 373) or reduced intensity conditioning (RIC; n = 539) regimens.Results: The median follow-up was 31.1 and 25.7 months for MAC and RIC, respectively. The incidence of relapse and nonrelapse mortality (NRM) were 25.1% versus 28.7% and 31.0% versus 30.3% for MAC and RIC, respectively; 2-year leukemia-free survival (LFS) was 43.9% for MAC versus 41.0% for RIC. In multivariate analysis, the use of MAC versus RIC was not associated with a difference in the outcomes. Results were confirmed in the propensity score-weighted analysis. Disease status and performance status at transplantation were associated with outcomes. Notably, the use of posttransplantation cyclophosphamide was associated with reduced acute graft-versus-host disease (aGVHD) stage III-IV, and NRM and increased overall survival, LFS, and GVHD-free, relapse-free survival. The use of mobilized peripheral blood stem cells was associated with an increased risk of stage II-IV aGVHD.Conclusion: No differences were found between MAC and RIC regimens for haplo-SCT in adults with AML who were ≥45 years of age. The type of GVHD prophylaxis, disease status, and performance status were the major predictors of transplantation outcome. These results may serve as the background for randomized study comparing RIC versus MAC for haplo-SCT in adults with AML. [ABSTRACT FROM AUTHOR]

The introduction of novel agents in the management of multiple myeloma and related plasma cell dyscrasias has changed our treatment approaches and subsequently the outcome of patients. Due to current advances, the European Myeloma Network updated the diagnostic and therapeutic recommendations for patients with Waldenström's macroglobulinemia (WM), AL-amyloidosis, monoclonal immunoglobulin deposition disease (MIDD), POEMS syndrome, and primary plasma cell leukemia. For patients with WM, the combination of rituximab with chemotherapy remains the treatment cornerstone, while the Bruton-tyrosine kinase inhibitor ibrutinib has been introduced and approved for relapsed/refractory disease. The management of light chain amyloidosis depends on the presence and severity of heart disfunction. If present, intensification with an autologous stem cell transplantation (ASCT) is not recommended. Further aggregation of misfolded light chains could be prevented by doxycycline or monoclonal antibodies targeting amyloid deposits. Initial treatment generally consists of melphalan/dexamethasone or bortezomib-based regimens. For relapsing patients, one can consider proteasome inhibitors, immunomodulatory agents, melphalan or daratumumab. Because intact or light-chain immunoglobulins are also the culprits for MIDD, the small monoclonal plasma cells' clones should be treated and generally respond well to bortezomib-based treatment. POEMS syndrome is a well-defined clinical entity that can present as solitary bone lesions or disseminated disease. Radiation therapy is used for patients with localized disease and result in long-lasting response. Systemic treatment should be proposed to patients with disseminated disease, but regimens that can worsen a pre-existing polyneuropathy should be avoided. PPCL is located at the other end of the spectrum of plasma cell disorders and is associated with an aggressive disease course and poor prognosis. It requires an imminent, multi-phase and novel agents-based therapy, including induction, ASCT, consolidation and maintenance, with short treatment-free intervals. Patients not eligible for transplant procedures require personalized, intensive therapeutic approach. Allogeneic stem cell transplantation can be used in selected patients.

Survival of myeloma patients has greatly improved with the use of autologous stem cell transplantation and novel agents, such as proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. Compared to bortezomib- and lenalidomide-based regimens alone, the addition of high-dose melphalan followed by autologous transplantation significantly improves progression-free survival, although an overall survival benefit was not observed in all trials. Moreover, follow up of recent trials is still too short to show any difference in survival. In the light of these findings, novel agent-based induction followed by autologous transplantation is considered the standard upfront treatment for eligible patients (level of evidence: 1A). Post-transplant consolidation and maintenance treatment can further improve patient outcome (1A). The availability of several novel agents has led to the development of multiple combination regimens such as salvage treatment options. In this context, the role of salvage autologous transplantation and allotransplant has not been extensively evaluated. In the case of prolonged remission after upfront autologous transplantation, another autologous transplantation at relapse can be considered (2B). Patients who experience early relapse and/or have high-risk features have a poor prognosis and may be considered as candidates for clinical trials that, in young and fit patients, may also include an allograft in combination with novel agents (2B). Ongoing studies are evaluating the role of novel cellular therapies, such as inclusion of antibody-based triplets and quadruplets, and chimeric antigen receptor-T cells. Despite encouraging preliminary results, longer follow up and larger patient numbers are needed before the clinical use of these novel therapies can be widely recommended., (Copyright© 2018 Ferrata Storti Foundation.)

Over the past two decades, not only treatment options, but also the diagnosis, staging, and risk assessment of multiple myeloma (MM), have undergone significant development, partially due to a deeper understanding of MM pathogenesis. Conventional cytogenetics and fluorescence in situ hybridization are routinely assessed in MM, and when combined with ISS stage may attain an even better predictive potential. In order to achieve even more effective and individualized therapies, one crucial goal is the identification of genes and gene combinations that predict for response or resistance to chemotherapy. High-dose chemotherapy with autologous stem cell transplant (SCT) still remains the standard therapy for younger patients, with novel agents now being included in both pre-transplant regimens and post-transplant consolidation/maintenance approaches. Similarly, novel agents are also being incorporated into allogeneic SCT for selected patients. In the treatment of elderly patients with MM, novel agents have been successfully incorporated into less intensive regimens, including melphalan/prednisone, low-dose dexamethasone, and cyclophosphamide/dexamethasone. While second-generation proteasome inhibitors are currently being intensively investigated, the subcutaneous administration of bortezomib, being equivalent to the established i.v. route, is now entering clinical practice. Supportive care remains a crucial aspect in the management of MM. The European Myeloma Network Trialist Group aims to address these contemporary aspects in MM.