How to Treat High-Risk Myeloma at Diagnosis and Relapse

Abstract

Survival in multiple myeloma has improved greatly during the past 2 decades, but this change has primarily benefited patients who have standard-risk disease. Patients with high-risk disease remain a challenge to diagnose and treat. To improve their clinical outcomes, it is imperative to develop tools to readily identify them and to provide them with the most effective available treatments. The most widely used stratification system, the revised International Staging System, incorporates serum β-2 microglobulin, albumin, lactate dehydrogenase, and high-risk chromosomal abnormalities [del(17p), t(4;14), and t(14;16)]. Recent updates have included mutational status and chromosome 1q abnormalities. Plasma cell leukemia, extramedullary disease, circulating plasma cells, renal failure, and frailty are also associated with poor outcome. The treatment approach for a newly diagnosed patient with high-risk multiple myeloma should include induction therapy, autologous stem cell transplantation if appropriate, and maintenance therapy. Triplet therapy with a proteasome inhibitor, immunomodulatory drug, and steroid, with or without an anti-CD38 antibody, should be considered for induction, along with a proteasome inhibitor and/or immunomodulatory drug for maintenance. Aiming for a deep and sustained response is important. Similar principles apply at relapse, with close monitoring of response, especially extramedullary disease and active management of side effects, so that patients can continue therapy and benefit from treatment. Immune-based therapies, including autologous CAR T-cell–based therapies and bispecific antibodies, show promising activity in relapsed disease and are being actively explored in earlier disease settings. As the prognosis for high-risk disease remains poor, the future goal for this patient group is to develop specific clinical trials to explore novel approaches and therapies efficiently.

Second Revision of the International Staging System (R2-ISS) for Overall Survival in Multiple Myeloma: A European Myeloma Network (EMN) Report Within the HARMONY Project

“…1 In 2015, the Revised International Staging System (R-ISS) was introduced to develop a robust prognostic system on the basis of widely available biomarkers, and is now considered a standard risk stratification model for patients with newly diagnosed multiple myeloma (NDMM). 2,3 The R-ISS takes into account ISS (which integrates b2microglobulin levels and serum albumin to reflect tumor mass and renal function), 4 high-risk chromosomal abnormalities (CA) detected by interphase fluorescence in situ hybridization (FISH) [deletion(17p), translocation t(4;14)(p16;q32), or t(14;16)(q32;q23)], 5 and serum lactate dehydrogenase (LDH) levels. 6,7 The R-ISS identifies three groups: R-ISS I including ISS I without neither high-risk CA nor high LDH levels; R-ISS III including ISS III and either high-risk CA or high LDH levels; and R-ISS II including all the other possible combinations.…”

Urinary Beta-2-Microglobulin and Late Nephrotoxicity in Childhood Cancer Survivors

“…Furthermore, there are many studies investigating the role of β2M in kidney diseases of different etiology. It has been demonstrated that β2M concentration is elevated among individuals with systemic lupus erythematosus, beta thalassemia major, type 1 diabetes, acute appendicitis, and congenital lower urinary tract obstruction, among others [32][33][34][35][36]. In addition, β2M levels are used as a tumor marker, primarily in monitoring the treatment of multiple myeloma, a cancer that occurs typically in advanced age [37].…”

Association of IMWG frailty score with health-related quality of life profile of patients with relapsed refractory multiple myeloma in Italy and the UK: a GIMEMA, multicentre, cross-sectional study

“…Over the past few decades, research advances and the development of novel targeted therapies have contributed to markedly improved survival of patients with multiple myeloma. 1 However, the occurrence of relapse or disease progression is inevitable for most of these patients. 2 The clinical management of patients with relapsed or refractory multiple myeloma in routine practice is a Association of IMWG frailty score with health-related quality of life profile of patients with relapsed refractory multiple myeloma in Italy and the UK: a GIMEMA, multicentre, cross-sectional study major challenge.…”