EHA Library - The official digital education library of European Hematology Association (EHA)

Adrian Alegre - Chair Introduction

Multiple myeloma (MM) is a very heterogeneous disease, clinically, biologically, and genetically. In spite of that, MM is one of the hematological neoplasia with more clinical advances in recent years with a significant improvement for patient survival. These advances have been possible due to a better understanding of the landscape of the disease and the advent of new drugs with original mechanisms along with new strategies of early combined treatment, sequential, intensified and maintenance therapies and new tools for monitoring evolution. In this educational session the participant experts will review these aspects.
In first place N Munshi and cols , from Dana Farber Cancer Centre (USA) reviews the immunopathology of multiple myeloma. Multiple myeloma origin is related to antigen-driven processes. The myeloma cells have bidirectional and major interactions with the bone marrow microenvironment enhancing growth, survival and drug resistance. The targeting of the immune system could provide new and very effective therapeutic strategies for multiple myeloma.
In the second talk H Avet-Loseau, from the University Cancer Center of Toulouse (France) reviews the genetic classification of myeloma for prognostication and treatment selection. Genetic analyses are mandatory at the time of diagnosis, and probably also at relapse to define the prognosis. The mutational landscape in MM, which is mainly based on whole exome sequencing, have confirmed the genetic heterogeneity of MM, with no specific common mutation. The genetic profile information could be used to propose specific drug targeted combinations although this is still a matter of debate.
And finally, Dr J San Miguel from the Clínica Universidad de Navarra (Spain) and cols from a the Spanish Myeloma Group, review the new treatment approaches in myeloma in 2017. The outcome for MM patients has significantly improved in the last 15 years, mainly due to the use of proteasome inhibitors (bortezomib, carfilzomib, ixazomib) and immunomodulatory agents (thalidomide, lenalidomide, pomalidomide), and more recently, monoclonal antibodies (daratumomab, elotuzumab) and other novel drugs with a singular mechanism of action as HDAC inhibitors ( panobinostat). The combination of a MoAb plus a triplet based on a PI-IMiD-Dex could be the future standard for induction. Intensification with autologous stem cell transplantation (ASCT) is still the standard of care to enhace response rate and prolong PFS and OS. The options for treatment at relapse have also improved with immunotherapy strategies with check-point inhibitors as pembrolizumab, the use of anti-BCMA CAR-T and a large list of new promising investigational drugs. Moreover, the introduction of new criteria for early diagnosis with the option of early intervention are opening new therapeutic avenues. The new IMWG response criteria, with the concept of minimal residual disease, should contribute to individualized treatment based on highly sensitive methods for monitoring treatment efficacy. The treatment goal for multiple myeloma should be to find a balance between efficacy, toxicity and cost, with the ultimate aim of achieving a cure for the disease.

Learning Objectives of the manuscript
After viewing this presentation the participant will be able to:
- To understand the bidirectional interaction of mieloma cells with the bone marrow microenvironment and with the immune system and to highlight their therapeutic implications.
- To review the cytogenetics and molecular landscape of multiple myeloma and to know the main genetics tests required at diagnosis and at relapse to identify patients with high risk.
- To understand the advances observed during recent years due to the novel drugs including immunotherapy and their favourable clinical impact on survival,
and to learn about new biomarkers, to decide early treatment and new integrated tools for minimal residual disease monitoring.
- To understand the best option therapy for upfront myeloma patients candidates and non candidates for autologus hematopoeitic transplant including the role of consolitation and maintenance therapies, and the different options of rescue with new drugs for refractory/relapse patients.

Learning Objectives of the presentation
After viewing this presentation the participant will be able to:
- Describe the immune status in multiple myeloma.
- Discuss the impact of immune dysfunction on myeloma cell growth and survival.
- Elucidate various methods and mechanisms to augment immune function for potential therapeutic application.