Quality of life in patients with multiple myeloma after CAR-T cell therapy

Introduction

There are currently only two CAR T-cell therpies available for the treatment of relapsed or refractory multiple myeloma (MM). The first, idecabtagene vicleucel (ide-cel), was approved by the U.S. Food and Drug Administration (FDA) on March 31, 2021, while the second, ciltacabtagene autoleucel (cilta-cel), was approved on February 28, 2022.

Until recently, communications around these two treatments have focused on clinical management, patient selection, and safety; however, understanding their real-world impact has become increasingly important, especially in relation to quality of life (QoL) in patients with advanced stage disease.

During the 19th International Myeloma Society Annual Meeting held in Los Angeles, US, Sidana discussed the QoL for patients with MM following CAR T-cell therapy, covering the factors associated with posttherapy QoL, the changes experienced by patients undergoing therapy, and strategies to improve the patient experience. Below, we summarize the presentation.

Tools to assess QoL

Clinicians currently use questionnaires to assess the QoL of their patients. While there are several commonly used, including FACT-MM and SF-12, they all focus on collecting patient responses in key domains:

• physical function
• fulfilling functional roles
• emotional well being
• social interactions

Advantages of utilizing questionnaires to collect patient information include the uniform and validated data produced; however, they are often not individualized or therapy specific. An alternative approach is qualitative structured interviewing, which can be tailored for novel treatments, such as CAR T-cell therapy, and therefore provide more insight.

Factors affecting QoL

There are several factors that can impact QoL after CAR T-cell therapy, ranging from those experienced over a number of weeks to long-term factors experienced over several years. CAR T-cell therapy related factors include:

• CAR T-cell therapy toxicities
• infection and cytopenias
• delayed neurological toxicities
• secondary cancers
• other unknown effects

Disease related factors impacting QoL of life include:

• disease symptoms
• relapse

Patients also experience significant financial and social burdens both during and after therapy, often associated with treatment costs and the ongoing social impact of a chronic illness.

CAR-T clinical trials evaluating QoL

The accelerated approval of ide-cel and cilta-cel was based on data from pivotal trials in MM, several of which included patient-reported outcomes on QoL as secondary endpoints:

• Data from the KARMMA trial (NCT03361748) evaluating QoL after treatment with ide-cel showed an improvement in fatigue, pain, and physical and cognitive functioning over time in responding patients, as well as a clinically significant improvement in global health status and reduction in disease symptoms. Provided the patients remained disease free, these improvements were sustained long term.
• Results from the CARTITUDE-1 trial (NCT03548207), which evaluated QoL after treatment with cilta-cel, demonstrated that after an initial decline in physical function and global health status at Day 7 posttreatment, due to the initial increase in symptom burden, there was gradual improvement over time, with a similar trend for pain and fatigue. In several instances, improvements went beyond baseline levels.

These improvements were also shown in studies evaluating QoL during treatment received after progressing to CAR-T cell therapy. Initial declines in physical and functional domains compared to the median population, contrasted with the significant improvements seen between 1–3 months after therapy.

Patient-associated challenges

Several challenges remain in the management of QoL for patients with MM. The presence of persistent symptoms after CAR-T cell therapy has a significant impact on QoL; according to self-reported adverse events defined by the CTCAE guidelines, 85% and 93% of patients reported pain and fatigue of any grade at 6 months posttreatment, respectively.

Financial toxicity is also a heavy burden for patients throughout the treatment process. Sidana highlighted a study from the University of Wisconsin evaluating COST-FACIT scores over time for patients undergoing CAR T-cell therapy, findings demonstrated that a higher proportion of patients reported Grade 1–2 financial toxicity at 3 and 6 months posttreatment compared with baseline (Figure 1).

*Adapted from Sidana S.¹

Factors associated with financial toxicity include:

• insurance coverage
• relocation/lodging
• discretionary spending posttreatment

Strategies to improve QoL

Several strategies were suggested to improve the QoL of patients after treatment. Firstly, a multi-disciplinary approach involving doctors and nurse practitioners centered around patient education and social work support, followed by tailored interventions to reduce pain and fatigue; this could be achieved with exercise programs alongside electronic symptom and activity monitoring with real-time feedback. Finally, long-term rehabilitation plans which are developed and overseen in conjunction with the patient’s local doctor. A summary of rehabilitation strategies for patients undergoing CAR T-cell therapy has been recently published as a visual abstract on The Multiple Myeloma Hub.

Conclusion

The QoL of patients should be considered at all stages of CAR T-cell therapy. While disease and financial toxicities present a heavy burden for patients, there are several possible strategies that could provide relief and, with the development of long-term health plans, these can ensure patients are able to live a healthy and fulfilling life both during and after treatment.