Journal Article

A case for improving frail patient outcomes in multiple myeloma with phenotype‐driven personalized medicine

Forsberg, Peter A., Walker, Zachary J., Sherbenou, Daniel W., Babcock, Lyndsey R., Mark, Tomer M., Reiman, Lauren T.

2021

Overview

The treatment of older persons with cancer is fraught by a delicate balance of targeting the disease while avoiding treatment‐related complications. “Personalized,” or “precision” medicine approaches can ease this problem through more efficacious and less toxic treatments. Multiple myeloma epitomizes the struggle to balance treatment options and their complications, for it is an incurable disease afflicting a predominantly aged population, and treatment is administered on a continuous schedule with little or no breaks. Over the last two decades, advances in drug development have improved outcomes for younger, fit patients, but older, frail patients have not realized the same benefit. This could be related to the benefits of three drug combinations, when frail patients can often tolerate only two drugs at a time. In myeloma, personalized approaches have lagged behind some other malignancies due to its genetic complexity and a paucity of abnormalities with associated targeted therapies. In contrast, the disease is managed with an array of drugs that target phenotypic characteristics common in malignant plasma cells. To address the unmet need for personalized medicine in myeloma, we developed a functional approach by profiling the sensitivity of patients’ myeloma to clinically available drugs. Through this, we observed that receiving at least two effective drugs portended better outcomes, leaving those patients who can only tolerate two drug regimens without room for error. We now describe a frail patient's case and their drug sensitivity profile to illustrate how personalized treatment could have led to an improved disease course. Personalized treatment could provide the greatest survival improvements to older adults with cancers, such as multiple myeloma, through avoiding undertreatment, limiting attrition through subsequent lines of therapy, reducing exposure to ineffective drugs and streamlining the management of relapses. Exploring these avenues is imperative to closing the gap of cancer‐related mortality in older and frail persons. In comparison to the contemporary approach to multiple myeloma, personalized treatment has the potential to guide more efficient drug selection and disease targeting. Although three drug regimens have repeatedly proven superior in this disease, older adults often receive two drugs to minimize treatment‐related toxicities. Consequently, older adults are at risk to receive less effective treatment, contributing to their currently inferior outcomes. Here, we discuss Myeloma Drug Sensitivity Testing (My‐DST) as an approach to personalized treatment for Multiple Myeloma by distinguishing relative drug sensitivity (S) versus resistance (R) to the commonly used drugs for this malignancy. Through personalized therapy to optimize the ratio of effective drugs, older persons stand to derive the most benefit if we can minimize poor responses and side effects, simultaneously improving survival and quality of life (QOL) outcomes.

• Publisher: John Wiley & Sons, Inc,Wiley
• Subject: Activities of daily living / Age / aging / Bone marrow / Cancer therapies / Chemotherapy / Chromosomes / Clinical outcomes / Clinical trials / Decision making / Drug development / Drugs / Frailty / Genotype & phenotype / Geriatrics / Monoclonal antibodies / Multiple myeloma / Mutation / Older people / Patients / personalized medicine / Plasma / Population / Precision medicine / Stem cells