Choosing the Right Therapy for Patients with Relapsed/Refractory Multiple Myeloma (RRMM) in Consideration of Patient-, Disease- and Treatment-Related Factors

Abstract

Treatment of relapsed/refractory multiple myeloma (RRMM) is more complex today due to the availability of novel therapeutic options, mostly applied as combination regimens. immunotherapy options have especially increased substantially, likewise the understanding that patient-, disease- and treatment-related factors should be considered at all stages of the disease. RRMM is based on definitions of the international myeloma working group (IMWG) and includes biochemical progression, such as paraprotein increase, or symptomatic relapse with CRAB criteria (hypercalcemia, renal impairment, anemia, bone lesions). When choosing RRMM-treatment, the biochemical markers for progression and severity of the disease, dynamic of disease relapse, type and number of prior therapy lines, including toxicity and underlying health status, need to be considered, and shared decision making should be pursued. Objectively characterizing health status via geriatric assessment (GA) at each multiple myeloma (MM) treatment decision point has been shown to be a better estimate than via age and comorbidities alone. The well-established national comprehensive cancer network, IMWG, European myeloma network and other national treatment algorithms consider these issues. Ideally, GA-based clinical trials should be supported in the future to choose wisely and efficaciously from available intervention and treatment options in often-older MM adults in order to further improve morbidity and mortality.

Monitoring multiple myeloma in the peripheral blood based on cell-free DNA and circulating plasma cells

“…Most importantly, proteasome inhibitors, immunomodulatory agents, and therapeutic antibodies have led to improved survival rates and highly effective combination therapies including these substances have been implemented as first-line therapies [1][2][3]. Moreover, nuclear export inhibitors and chimeric antigen receptor T cells have shown promising results in clinical trials for patients with relapsed or refractory disease [3,4] and thus have been approved recently for MM. Therapeutic antibodies against CD38 and SLAMF7 such as daratumumab and elotuzumab are also increasingly applied as maintenance therapy due to their little side effects [5].…”

Allogeneic Stem Cell Transplantation in Multiple Myeloma

“…According to the European Society for Blood and Marrow Transplantation (EBMT) guidelines, high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-SCT) is the standard of care for these transplant-eligible patients with newly diagnosed MM [ 8 ]. Over the last decades, new effective therapeutic agents were developed, especially for elderly patients with relevant comorbidities ineligible for auto-SCT and those with relapsed and/or refractory multiple myeloma (RRMM) [ 9 , 10 , 11 ], including immunomodulatory drugs (IMID), proteasome inhibitors (PI), monoclonal antibodies, inhibitors of histone deacetylases, bispecific antibodies, chimeric antigen receptor T (CAR-T) cells and others [ 7 , 12 , 13 , 14 , 15 ]. Due to this remarkable increase of treatment options, and thus an often much deeper remission after optimized first-line therapy and the availability of effective salvage therapies, survival of MM patients has substantially improved over the last years [ 16 , 17 , 18 ].…”

Multidisciplinary tumor board analysis: validation study of a central tool in tumor centers

“…Since treatment options for tumor diseases, including multiple myeloma (MM), have improved considerably in recent years [7], cancer care has become more complex due to numerous therapeutic options. In addition, MM patients, with symptomatic disease and SLIM-CRAB criteria (≥ 60% clonal bone marrow plasma cells, involved/uninvolved free light chain (FLC) ratio of ≥ 100, MRI with > 1 focal lesion, hypercalcemia, renal insufficiency, anemia, osteolytic bone lesions), are often treated by different disciplines and require multidisciplinary care to coordinate complex therapeutic options [1,[8][9][10]. TBs represent an established way to meet this goal [1,[8][9][10].…”