Patient‐reported outcomes following autologous stem cell transplant for patients with multiple myeloma

Abstract We evaluated changes in patient‐reported outcomes and cognitive function from pre‐ to 3–6 months post‐treatment among 42 newly diagnosed patients with multiple myeloma undergoing transplant with complete data using PROMIS‐29. There were statistically significant improvements in physical (p < .001) and mental health (p < .001) but not cognition from pre‐treatment to 3–6 month follow‐up. Similar results were seen within age or comorbidity strata. Patients with myeloma undergoing transplant experienced generally improved short‐term health outcomes with no significant declines in cognition.


INTRODUCTION
In 2021, over 34,000 new cases of multiple myeloma and nearly 12,400 deaths are projected to occur. With recent advances in treatment, overall 5-year survival in patients with multiple myeloma is now 56% with most getting a transplant [1]. The standard of care for transplanteligible patients is induction therapy followed by consolidative highdose therapy with autologous stem cell transplantation (ASCT). The intensity and duration of treatment may cause severe short-term treatment toxicities, long-term symptoms, and a decline in physical and cognitive functions, especially among older patients [2][3][4][5][6]. With recent therapeutic advances extending survival, but increasing toxicity, evaluating how these treatments affect short-term patients will help promote informed decisions about treatment and identify areas for additional clinical support and intervention. We prospectively evaluated multiple domains of patient-reported outcomes among patients diagnosed with myeloma. Our primary aim was to describe pre-and post-transplant changes in terms of symptoms, functional deficits, and cognitive function in patients with multiple myeloma undergoing autologous stem cell transplant.

Participants
We enrolled patients with newly diagnosed symptomatic myeloma,

Procedures
Patients were recruited from October 2016 to February 2019 and were on average 4-months postdiagnosis. The first survey (T0) was given at the time of, or just prior to, induction therapy, but before ASCT, if ASCT was received. Follow-up assessments occurred at the first post-ASCT visit (T1), and approximately 1-month (T2), 3-and 6-months post-ASCT (T3 and T4, respectively). Participants who did not receive ASCT were followed at corresponding visits. Assessments were conducted either in person or using a secure, web-based application. A phonebased option was also available. All objective cognitive assessments were performed in person. Participants received a $20 gift card after the baseline assessment and another at completion of study assessments.

Primary outcomes
Five symptoms (fatigue, pain, depression, anxiety, and sleep disturbance) and two functional domains (physical and social function) were assessed using the patient-reported outcomes measurement information system (PROMIS ® ) Profile-29. This profile includes separate domain scores plus summary scores for physical and mental health.
We also included the PROMIS cognitive function domain (Cognitive are defined as clinically meaningful changes [7]. We used the 11-item comprehensive score for financial toxicity (COST) scale (ranging from 4 to 34) to quantify cancer patients' experience of financial distress [8].
We also asked patients about selected comorbid conditions.

Secondary outcomes and neuropsychological assessment
We used a validated battery of cognitive functioning tests to assess neuropsychological function. At T0 or T1 and T4, a trained research assistant administered the neurophysiological assessment in two selected domains: attention, processing speed, and executive function (APE); and learning and memory (LM) [9,10].

Covariates
We abstracted information from institutional electronic medical records to ascertain tumor-, treatment-, and transplant-related information, disease staging, and use of prior therapies. The survey was used to collect information on patient's sex, age, race, ethnicity, and comorbidity.

Analysis
We calculated proportions, means, and standard deviations for all vari-

Short-term outcomes
Among the 42 ASCT subjects, we observed statistically and clinically meaningful improvements in overall physical health (+5.9, p < .001) and mental health (+4.4, p < .001) from T0, before ASCT to T4, 6 months post-ASCT (Table 2). Improvements were reflected by changes in the physical and mental health summary domains, such as improved physical function scores, decline in physical symptoms (pain, fatigue), and decline in mental health symptoms (anxiety, depression). Changes in these individual domains were 3 points or greater, reflecting moderate to large effect sizes [11].

DISCUSSION
Results from this preliminary study suggest that patients with myeloma who receive ASCT experience either improvements or no change in several patient-reported outcomes. As expected, at baseline (T0), patients reported moderate to severe impairments in physical function, pain, and fatigue. All of these improved or resolved by the final assessment. Importantly, we observed overall improvement or resolution of

AUTHOR CONTRIBUTION STATEMENTS
NB, AP and RJ conceived and designed the work, contributed to data collection, data analysis, and interpretation, and drafting the article.
WZ contributed to data analysis and critical revision of the article.
JM contributed to conception of the work, data interpretation, critical TA B L E 2 Changes in patient-reported outcome symptom and functioning domain scores at baseline (T0) and the last assessment * among ASCT recipients (n = 42)

CONFLICTS OF INTEREST
The article was prepared as part of one of the author's (REJ) official duties as employees of the US Federal Government. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the National Cancer Institute. The