Navigating the treatment landscape in multiple myeloma: which combinations to use and when?

Abstract

Multiple myeloma is one of the most common hematological malignancies, affecting mainly elderly patients. The treatment landscape for the management of this disease has evolved significantly over the past 15 years, and a vast array of therapeutics is now available, including immunomodulatory drugs, proteasome inhibitors, histone deacetylase inhibitors, and monoclonal antibodies. As a result, deciding which drugs to use and when, and whether these should be used in a particular order or combination, can be challenging. Although combination regimens are often associated with deeper responses and better long-term outcomes than monotherapy, and are becoming the standard of care, they may result in significant incremental toxicity; hence, a sequential approach may be more appropriate for some patients. In particular, treatment choices can vary depending on whether the patient has newly diagnosed multiple myeloma, is eligible for transplant, has relapsed and/or refractory multiple myeloma, or is considered to have high-risk disease. In this review, we discuss factors to be taken into account when making treatment decisions in each of these settings. We also briefly discuss possible therapeutic strategies involving agents that may become available in the future.

Towards the integration of patient-reported outcomes into the global clinical management of multiple myeloma

“…In addition, one should consider that oral therapies will increasingly be used, therefore adding other important challenges with regard to patients' management. Indeed, several highly effective drugs are also available as oral agents and their use can improve patient's management, although they are typically more expensive than parenteral compounds [1,2]. In addition, subcutaneous administrations are also increasingly compared to intravenous (IV) long infusions, representing this route another good option to facilitate patient's management.…”

“…In addition, subcutaneous administrations are also increasingly compared to intravenous (IV) long infusions, representing this route another good option to facilitate patient's management. Therefore, compared to the recent past, a wide range of treatment agents is now available and several other therapeutic approaches, such as chimeric antigen receptor T (CAR-T) cell therapy and Immune checkpoint inhibitors [1,2], are under development. As a result of the introduction of novel agents, the clinical outcome of MM has significantly improved and, for many of patients, the disease has turned into a long-term chronic condition characterized by clinical remissions alternated with relapses [1,2].…”

“…Therefore, compared to the recent past, a wide range of treatment agents is now available and several other therapeutic approaches, such as chimeric antigen receptor T (CAR-T) cell therapy and Immune checkpoint inhibitors [1,2], are under development. As a result of the introduction of novel agents, the clinical outcome of MM has significantly improved and, for many of patients, the disease has turned into a long-term chronic condition characterized by clinical remissions alternated with relapses [1,2]. Given that MM typically affects elderly patients with approximately one-third of patients being older than 75 years at the time of diagnosis, the incidence is rising due to population aging [3].…”

“…Therefore, their frailty, which may include the decline in functional capacities due to diseaserelated symptoms as well as to medical comorbidities, cognitive impairment, and polypharmacy, should be carefully considered to best evaluate potential implications for treatment discontinuation, therapeutic efficacy, and health-related quality of life (HRQOL) impact [3][4][5][6]. During their disease history, many MM patients may receive multiple lines of therapies and live with their illness for many years experiencing disease complications as well as treatment-related symptoms [1,2,5]. Briefly, patients with newly diagnosed MM (NDMM), according to their fitness, should receive a frailty-oriented treatment [3], which often consist of a combination of drugs with specific toxicity profiles [1][2][3][4][5][6].…”

“…During their disease history, many MM patients may receive multiple lines of therapies and live with their illness for many years experiencing disease complications as well as treatment-related symptoms [1,2,5]. Briefly, patients with newly diagnosed MM (NDMM), according to their fitness, should receive a frailty-oriented treatment [3], which often consist of a combination of drugs with specific toxicity profiles [1][2][3][4][5][6]. Therefore, effective treatment options in MM can help maintain HRQOL by influencing treatment response levels and delaying disease progression [1,3].…”