Quality of Life after HCT – What can an outcomes registry do? Douglas Rizzo, MD MS October 20, 2016

CIBMTR Number of Patients Registered, 1970-2015 Updated SK/RD 1/30/14

What are the outcomes ?

What are the outcomes of HCT? Overall survival is gradually improving BUT, there is more to the story ….

Number of HCT Survivors Increasing Estimated ~110,000 HCT survivors in the US in 2009 ~5X increase by 2030 if transplant rates stay stable NS Majhail et al, BBMT 2013

Long-term Survival after HCT Reference Patients Overall Survival CGVHD & Mortality Risk Life Expectancy AUTOLOGOUS HCT Bhatia et al (2007), BMT-SS N=854, multiple ds (≥2 yr survivors) 69% @ 10 yrs -- Same (for select pts) Majhail et al (2009), CIBMTR N=1367, lymphoma 52-85% @ Same ALLOGENEIC HCT N=1479, multiple ds (≥2 yr survivors) 80% @ 15 yrs √  @ 15 yrs Goldman et al (2010), CIBMTR N=2444, CML (≥5 yr survivors) 87-88% @ Wingard et al (2011), CIBMTR N=10632, multiple ds 80-92% @ COMBINED Martin et al (2010), FHCRC N=2574, multiple ds 20 yrs  @ 30 yrs

Burden of Late Morbidity Late complications are significant issue for survivors BMT-SS – 1022 auto and allo HCT 2-year survivors Cumulative incidence of chronic health conditions CL Sun et al, Blood 2010 ; 116: 3129

Late morbidity after HCT: Patients report broad array of impairments, including: Cognitive deficits Sexual dysfunction Emotional distress Fatigue and sleep disturbances Social engagement Inability to return to work/disability Financial difficulties Significant impact on quality of life

Key Question 4: Are there new measures of quality not currently reported publicly by the CIBMTR which should be included in future iterations of the center-specific survival analysis (with risk adjustment) on behalf of the HCT community?

KQ4: New quality measures? Develop and test a 3 year risk adjusted overall survival measure – pilot for center use Work in progress: pilot testing underway for 2015 Report (HCT 2009-2013) Assess feasibility of collecting and reporting Patient Reported Outcomes QOL pilot analysis in final manuscript phase Exploring tools by which CIBMTR and centers can collect these data EMR or PROMIS (NIH)

Centralized patient reported quality of life collection in HCT patients is feasible, and higher pre-HCT scores significantly predict better overall survival post-transplant Bronwen Shaw, MD PHD Professor of Medicine, MCW Senior Scientific Director, CIBMTR There are no conflicts of interest to disclose.

Background and Aims Patient Reported Outcomes (PRO) are associated with outcomes after HCT, but are not routinely collected in outcomes registries Primary Aim: A pilot project to evaluate the feasibility of prospective collection of PRO at 8 transplant centers reporting clinical data to the CIBMTR Secondary Aim: To correlate PRO with clinical and demographic data routinely collected

Study Schema

Patients and Methods Standard pre-transplant, treatment variables and clinical outcomes were collected (CIBMTR forms completed by centers) Additional socio-demographic form at baseline PRO measures: Adults: FACT-BMT and SF36 Children/parents: age appropriate and proxy PedsQL modules A satisfaction survey was completed by participants at 12 months

Time point retention Adults Pediatrics Pre-HCT Day 100 6/12 1 year Total received 295 173 163 136 Total approached 301 238 202 174 Overall retention rate 98.01% 57.48% 54.15% 45.18% Time point retention rate 72.69% 80.69% 78.16% Pediatrics Pre-HCT Day 100 6/12 1 year Total received 78 50 43 Total approached 89 85 79 72 Overall retention rate 87.64% 56.18% 48.31% Time point retention rate 58.82% 63.29% 59.72%

Change in QOL over time

Factors associated with survival In adults baseline FACT-BMT and PCS of SF36 were associated with overall survival and QoL at 1 year Baseline MCS was not significantly associated with OS Effects in children are less marked, but follow the same pattern   PRO Score pre-HCT (higher is better) RR of mortality (95%CI) p-value FACT-BMT (adult) 10 point increase 0.83 (0.75 - 0.92) 0.0003 PCS of SF36 (adult) 0.78 (0.64 - 0.95) 0.0147 PedsQL (child) 0.69 (0.48 - 0.99) 0.0444 PedsQL (parent) 0.79 (0.60 - 1.03) 0.0816

Conclusions Feasible to prospectively collect PRO directly from patients at multiple time points High enrollment and return rate Good patient satisfaction and ongoing interest Baseline PROs are significantly associated with survival and post transplant QoL after adjusting for clinical factors Routine collection of PRO adds value to current clinical data

Why collect PRO? BMT CTN 0201: RCT of PB v BM for UNR donors

How can PRO fill the picture - 0201 5 year follow-up with patient reported data No difference Relapse, TRM, OS BM recipients more likely to return to work (OR 1.5; 95% CI 1.2-2.0) Lee SJ et al. JAMA Oncology online Aug 2016

Other studies where PRO associated with OS: CTN 0902 But: No differences in SF-36 PCS or MCS, or other PRO at day 100 with either exercise or stress reduction interventions Wood, WA et al. Cancer;122:91-98, 2016

NIH BMT Late Effects Consensus Recommendations Quality of Life and Psychosocial Working Group

Outcomes: Recommendations Research directions: Integrate assessment of key and understudied outcomes (e.g. depression/distress, physical function, cognitive function, pain syndromes, financial toxicity) into standard and new clinical protocols examining therapies, preparative regimens and cGVHD prophylaxis and treatment. Implement multicenter longitudinal studies with standardized measures and time points to improve knowledge of high prevalence/impact outcomes in pediatrics and non-malignant conditions (otherwise always small sample sizes) and other understudied populations.

Can we leverage the CIBMTR data collection platform to collect PRO more routinely?

What can we do in the future? Explore a direct-to-patient interface to collect PRO from patients and connect those data to robust clinical data regarding their HCT Use the same “core” PRO measures in all research studies of HCT patients Consider core and variable measures Use a system which is free, easy to access (?PROMIS ?) Ensure a low burden for centers (and patients) Use a single system of items which is versatile Flexible, change over time Shaw, BE et al; Harmonization of HRQOL in HCT; BMT May 2016

Vision-Mission: Vision Mission The Patient-Reported Outcomes Measurement Information System (PROMIS®), funded by the National Institutes of Health, aims to provide clinicians and researchers access to efficient, precise, valid, and responsive adult- and child-reported measures of health. Mission PROMIS uses measurement science to create an efficient state-of-the-art assessment system for self-reported health.

The PROMIS of a better future… A publicly available, adaptable and sustainable Internet-based system that will: Administer individually “tailored” questionnaires (using Computer Adaptive Testing (CAT) technology) to measure health status outcomes Collect and analyze responses Provide instant health status reports to users to: Enhance research Improve clinical decision-making Facilitate policy-making by health plan and systems and public programs

How will this help? Standardized, adaptable, longitudinal PRO data collection to: Characterize the PRO deficits patients experience – including to plan interventions Utilize patient-reported status as a more accurate and representative measure of patients’ health status in multivariate analyses Analyze effectiveness of various interventions across broad group of transplant centers Comparison group for non-randomized interventions

High priority questions to address What role can centers play in data collection? What is the real purpose for collection of QOL Research? Understanding the “holistic” patient experience? Public reporting? Do we understand Quality of Life well enough to make it publicly reportable What are the unintended consequences? Funding $$$

QOL reference slides

What is a PRO? Patient-reported outcomes (PROs) are generally understood to encompass symptoms, functional status, and perceptions of health status or health-related quality of life (HRQoL) as reported directly by the patient without interpretation from clinicians (http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugDevelopmentToolsQualificationProgram/ucm370262.htm; accessed 2 July 2015).

Patients Selection criteria for analysis Excluded Included Total number approached to be in study   390 Transplant never occurred 28 Canceled (21) Deceased (7) 362 Patients withdrew before completing baseline or transplant 6 356 Patients consented to study but did not returned any surveys  5 351 Returned incomplete FACT-BMT baseline measure (not scorable) 4 347 QOL: Patients did not fill out baseline measure 7 340

Demographics Adults Pediatrics Gender Male 154 (58) 45 (54) Female   Male 154 (58) 45 (54) Female 110 (42) 38 (46) Race Caucasian 236 (89) 67 (81) Other 26 (10) 15 (18) Unknown/declined 2 (<1) 1 (1) Karnofsky/Lansky performance score ≥90% 158 (60) 73 (88) <90% 106 (40) 10 (12) Sorror score 63 (24) 55 (66) 1 -2 93 (35) 19 (22) = or > 3 101 (37) 7 (8) Missing 7 (3) 2 (2) Marital status (adults only) Married or living with partner 182 (69) N/A Single/separated/divorced/widowed 55 (21) 27 (10) Household income level < 60,000 52 (20) 36 (43) ≥60,000 78 (30) 29 (35) 134 (50) 18 (22) Median follow-up of survivors (range), months 26 (8-38) 25 (6-46)

Demographics Adults Pediatrics Indication for transplant   Acute leukemia 130 (49) 32 (39) CML 19 (7) 1 (1) MDS/MPS 49 (19) 4 (5) Other leukemia 20 (8) NHL 22 (8) HD 6 (2) Multiple myeloma 7 (3) Non-malignant diseases 11 (4) 46 (55) Myeloablative conditioning regimen No 125 (47) 23 (28) Yes 139 (53) 60 (72) TBI use 150 (57) 53 (64) 114 (43) 30 (36) Donor Matched relative 104 (39) 12 (14) Mismatched relative 4 (2) Matched URD 105 (40) 51 (61) Mismatched URD 7 (8) Cord blood 29 (11) Year of transplant 2011 25 (9) 9 (11) 2012 185 (70) 55 (66) 2013 54 (20) 19 (23)

Baseline QOL scores Adults Pediatrics Completed baseline QOL survey (FACT-BMT for adults PedsQL for children)   No 1 (<1) 6 (7) Yes 263 (99) 77 (93) Median (range) Baseline FACT-BMT score 104 (53-148) N/A Baseline SF36-PCS (higher is better) < 50 193 (73) ≥ 50 63 (24) Missing 8 (3) Baseline SF36-MCS (higher is better) 118 (45) 138 (52) Baseline PedsQL self-reported < 69.7 28 (34) ≥ 69.7 24 (29) 7 (8) N/A – children under age 5 Baseline PedsQL proxy reported < 65.4 36 (43) ≥ 65.4 38 (46) 9 (11)

Factors associated with feasibility Adults: Factors negatively associated with retention were race other than Caucasian (OR 0.21; CI 0.12-0.36; p<0.0001) and unmarried status (OR 0.41; CI 0.25-0.65; p=0.0002) Pediatrics: Higher family income (OR 4.72; CI 1.98-11.25; p=0.0005) was positively associated with retention

Adjusted OS by FACT baseline quartile

Conclusions Feasible to prospectively collect PRO at multiple time points for unselected transplant patients High return rate Good patient satisfaction Baseline PROs are significantly predictive of survival and post transplant QoL adjusting for clinical factors Routine PRO adds value to current clinical data collection

NIH PROMIS