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The introduction of new agents and management strategies over the past decade has resulted in a major step change in treatment outcomes with deepening responses and increased survival for patients with multiple myeloma. In daily clinical practice, healthcare professionals are now faced with challenges including, optimal treatment sequencing and changing treatment goals. In light of this, a group of experts met to discuss diagnostic and treatment guidelines, examine current clinical practice, and consider how new clinical trial data may be integrated into the management of multiple myeloma in the future. © 2018 the Author(s). Published by Wolters Kluwer Health, Inc.

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 as salvage treatment options. In this context, the role of salvage autologous transplantation and allotransplant have not been extensively evaluated. In 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 preliminary encouraging results, longer follow-up and larger patient numbers are needed before their clinical use can be widely recommended.

Multiple myeloma is a disease typical of the elderly, and, because of the increase in life expectancy of the general population, its incidence is expected to grow in the future. Elderly patients represent a particular challenge due to their marked heterogeneity. Many new and highly effective drugs have been introduced in the last few years and results from clinical trials are promising. Besides the availability of novel agents, a careful evaluation of elderly patients showed to be a key factor for the success of therapy. A geriatric assessment is a valid strategy to better stratify patients. In particular, different scores are available today to appropriately assess elderly patients and define their fitness/frailty status. The choice of treatment—transplantation, triplets, doublets, or reduced-dose therapies including novel agents—should depend on the patient’s fitness status (fit, intermediate-fit or frail). Second-generation novel agents have also been evaluated as salvage therapy in the elderly, and these new agents certainly represent a further step forward in the treatment armamentarium for elderly patients with multiple myeloma. © 2018, Macmillan Publishers Limited, part of Springer Nature.

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. © 2018, Springer Nature Limited.

The microenvironment in the bone marrow — including lymphocytes — is part of the pathophysiology of multiple myeloma (MM). High dose chemotherapy followed by autologous stem cell transplantation is standard of care for younger patients. Aim: To determine the influence of reinfused lymphocyte subsets on event free survival (EFS) and overall survival (OS). Methods: In peripheral blood (PB) and aphaeresis products (AP) of 41 MM patients lymphocyte subsets were determined by flow cytometry and were correlated with clinical outcome. Results: PB lymphocyte subsets did not influence EFS or OS. Residual plasma cells in the AP were not correlated with poor outcome, whereas a high percentage of B cells (CD19+) showed a trend towards reduced EFS (P = 0.051). A high amount of CD4 cells and an increased CD4/CD8 ratio were significantly associated with prolonged EFS. In contrast, high percentage of HLA-DR positive lymphocytes showed negative impact on EFS and OS (P = 0.03 and 0.02, respectively). Conclusion: Obtained data suggest the non-activated (HLA-DR negative) helper CD4+ T cells in the AP to be tumour protective. Микроокружение в костном мозге, включая лимфоциты, оказывает влияние на патофизиологию множественной миеломы (MM). Высокодозовая химиотерапия, за которой следует аутологическая трансплантация стволовых клеток, является стандартным подходом при лечении более молодых пациентов. Цель: изучить влияние введенных субпопуляций лимфоцитов на безрецидивную выживаемость (EFS) и общую выживаемость больных c ММ. Методы: методом проточной цитофлуориметрии в периферической крови (PB) и продуктах афереза (АР) пациентов с ММ ( n = 41) изучали субпопуляции лимфоцитов и возможную корреляцию с исходом болезни. Результаты: субпопуляции лимфоцитов РB не влияли на EFS или OS. Остаточные клетки плазмы в АР не коррелировали с плохим прогнозом, в тоже время при высоком содержании В-клеток (CD19+) отмечали тенденцию к снижению EFS (P = 0,051). Высокое содержание CD4-клеток и увеличение соотношения CD4/CD8 были достоверно ассоциированы с повышением EFS. В отличие от этого, высокий процент HLADR-положительных лимфоцитов имел отрицательное влияние на EFS и OS (P = 0,03 и 0,02 соответственно). Выводы: полученные данные позволяют предположить, что неактивированные (HLA-DR-отрицательные) хелперные CD4+ T-клетки в AP могут обладать антиопухолевыми свойствами.