Multiple myeloma, a quintessential malignant disease of aging: a geroscience perspective on pathogenesis and treatment

Abstract

Multiple myeloma (MM) is an incurable plasma cell malignancy, which is predominantly a disease of older adults (the median age at diagnosis is 70 years). The slow progression from asymptomatic stages and the late-onset of MM suggest fundamental differences compared to many other hematopoietic system-related malignancies. The concept discussed in this review is that age-related changes at the level of terminally differentiated plasma cells act as the main risk factors for the development of MM. Epigenetic and genetic changes that characterize both MM development and normal aging are highlighted. The relationships between cellular aging processes, genetic mosaicism in plasma cells, and risk for MM and the stochastic processes contributing to clonal selection and expansion of mutated plasma cells are investigated. In line with the DNA damage accumulation theory of aging, in this review, the evolution of monoclonal gammopathy to symptomatic MM is considered. Therapeutic consequences of age-dependent comorbidities that lead to frailty and have fundamental influence on treatment outcome are described. The importance of considering geriatric states when planning the life-long treatment course of an elderly MM patient in order to achieve maximal therapeutic benefit is emphasized.

A case report: Nonsecretory multiple myeloma presenting with bone pain

“…It is often caused by bone pain, which can occur in a single or multiple parts of the body, most commonly in the vertebral body, skull, ribs, pelvis, and proximal long bone. [ 8 , 9 ] Multiple osteolytic lesions can be seen in the affected bones, causing pathological fractures, vertebral collapse, spinal cord compression, etc, [ 10 , 11 ] which are easily misdiagnosed as osteoporosis, fracture, cervical and lumbar diseases, and bone metastatic cancer. As a rare disease in clinical practice, the misdiagnosis rate of NSMM is as high as 80%, among which bone pain ranks first among all misdiagnosed symptoms.…”

Case Report: Effective management of adalimumab-induced acquired hemophilia A with the CyDRI protocol

“…The median age of patients experiencing AHA onset due to drug exposure is typically around the age of 75 years [ 10 ]. The increased prevalence of autoimmunity in older individuals may be attributed to several factors related to the aging process, including immunosenescence [ 35 ], chronic low-grade sterile inflammation (“inflammaging” [ 36 , 37 ]), cumulative environmental exposure [ 38 ], clonal hematopoiesis of indeterminate potential (CHIP) [ 39 ], age-related thymus involution and hormonal changes. Importantly, there is generally a median period of about 30 days from the start of the implicated medication to the emergence of AHA symptoms [ 10 ].…”

Diagnostic and Prognostic Value of PACAP in Multiple Myeloma

“…Aging processes and many harmful environmental variables may presumably cause a pathological reduction in PACAP with age [ 62 , 63 ]. However, the evolution of manifest MM from asymptomatic forms (MGUS, SMM) is an extremely slow process, and prolonged progression leads to clonal heterogeneity of tumor cells, which also significantly compromises the efficacy of therapy and limits clinical options [ 4 ]. Therefore, treating elderly, polymorbid patients with poor performance status is a major challenge [ 64 , 65 ].…”

“…This occurs through the development of monoclonal gammopathy of unknown significance (MGUS) and smoldering myeloma (SMM), leading to an active MM that requires treatment [ 3 ]. Given the affected population, aging is also thought to play an important pathologic role in the development of the disease [ 4 ]. After induction therapy, autologous hematopoietic stem cell transplantation (ASCT) provides the longest progression-free survival (PFS) in the treatment setting.…”