Patient-Reported Outcomes in Long-Term Survivors of Autologous Hematopoietic Cell Transplantation for Multiple Myeloma: Secondary Analysis of Two Randomized Controlled Trials on Survivorship Care Plans
Authors: Chakraborty Rajshekhar , Rybicki Lisa A. , Preussler Jaime M. , Devine Steven , Baker K. Scott , Syrjala Karen , Yi Jean C. , Whitten Jennifer L , Shaw Bronwen E. , Majhail Navneet S. 
Published: November 2021

Abstract
Background: With advances in multiple myeloma therapy, approximately 1/3 rd of patients receiving frontline autologous hematopoietic cell transplantation (AHCT) are alive and progression-free at 8 years (Perrot et al. ASH. 2020). Although patient-reported outcomes (PROs) with induction therapy and early after AHCT are well-described, little is known regarding PROs in long-term disease-free survivors specifically in myeloma. The objective of our study was to assess health-related quality of life (HRQoL), distress, and healthcare care adherence (HCA) in myeloma survivors who are in a stable remission after AHCT.
Methods: The data were obtained from two randomized controlled trials (RCTs), namely, SCP (Survivorship Care Plan) and INSPIRE (Internet and Social media Program for Long Term Hematopoietic Cell Transplant Survivors). Both RCTs enrolled patients who are in a stable remission 1-10 years after AHCT. Our primary objective was to evaluate patient-reported HRQoL, distress and HCA. The secondary objective was to examine association of PROs with available patient (age, sex, race, body mass index [BMI], and health behaviors) and transplant (time since AHCT) variables. BMI was categorized as obese (≥30), overweight (25-29.9), and normal/underweight (&lt;25). HRQoL was assessed by SF-12 v 2 as physical component summary (PCS) and mental component summary (MCS) T scores, with higher scores indicating better functioning and a general population mean of 50 (Standard Deviation [SD] 10). Distress was assessed by Cancer and Treatment-Related Distress (CTXD) instrument, which reports mean scores from 0 to 3, with higher scores indicating greater distress. A CTXD score &gt;1.10 was considered as clinically significant distress based on prior data. HCA was assessed by a standard questionnaire, with scores from 0-1, indicating the proportion of age/sex-specific recommendations adhered to.
Results: A total of 345 patients were included, with the median age at AHCT of 61 years (range, 29-76). Median time from AHCT to study entry was 4 years (1.4-11.0). The mean (SD) PCS and MCS T-scores in the study population were 45.5 (±10.5) and 51.3 (± 10.1) respectively, compared to general population T-score of 50 (±10) for both (p-value for differences being &lt;0.001 and 0.021 resp.; Figure 1). The mean CTXD distress score was 0.9 (± 0.6), with 32% of patients having a score of ≥1.1, indicating clinically significant distress. The two CTXD domains with highest burden of clinically significant distress were "Health Burden" and "Uncertainty" (Figure 2). The proportion of patients who met guideline for tobacco, alcohol, exercise, sunscreen, and diet were 94%, 92%, 33%, 23%, and 13% respectively. The proportion of patients who were obese, overweight, normal weight, and underweight was 31.2%, 40.5%, 27.7%, and 0.6% respectively.
On multivariable analysis (MVA), factors significantly associated with decreased PCS score were obesity (Parameter Estimate [PE]: -5.0 [±1.6]; p=0.002) and meeting alcohol guidelines (PE: -4.2 [±2.0]; p=0.039), while meeting exercise guidelines was associated with a higher PCS score (PE: 3.4 [±1.3]; p=0.007). Obesity was significantly associated with a decreased MCS score (PE: -3.0 [±1.5]; p=0.05) and meeting sunscreen guidelines was associated with an increased MCS score (PE: 3.0 [±1.4]; p=0.029). Factors associated with lower distress were years since AHCT (PE: -0.04 [±0.02]; p=0.024) and meeting sunscreen guidelines (PE: -0.21 [+/-0.8]; p=0.005). Notably, increased time since AHCT was associated with lower distress in all domains except for identity and medical demands. Better overall HCA was associated with older age (PE: 0.005 [±0.0001]; p&lt;0.001) and female sex (PE: 0.04 [±0.02]; p=0.01) on MVA.
Conclusion: To our knowledge, this is the first study to characterize PROs in long-term myeloma survivors post-AHCT. Myeloma survivors have significantly worse physical HRQoL compared to general population but comparable mental HRQoL. Approximately 1/3rd are obese, with obesity being associated with worse physical and mental HRQoL. The inverse association between physical HRQoL and meeting alcohol guidelines could be secondary to abstinence from heavy drinking in those with poor physical functioning. Survivorship programs should address ongoing issues of health burden and uncertainty in myeloma survivors, encourage exercise and physical activity, and focus on groups at risk of poor HCA.
Figure 1 Figure 1.

Disclosures
Devine: Johnsonand Johnson: Consultancy, Research Funding; Magenta Therapeutics: Current Employment, Research Funding; Orca Bio: Consultancy, Research Funding; Be the Match: Current Employment; Sanofi: Consultancy, Research Funding; Tmunity: Current Employment, Research Funding; Vor Bio: Research Funding; Kiadis: Consultancy, Research Funding. Shaw: mallinkrodt: Other: payments; Orca bio: Consultancy. Majhail: Incyte Corporation: Consultancy; Anthem, Inc: Consultancy.