-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

3909 Patient-Reported Outcomes (PROs) Among Patients With Steroid-Refractory or -Dependent Chronic Graft-vs-Host Disease (cGVHD) Randomized to Ruxolitinib (RUX) vs Best Available Therapy (BAT)

Program: Oral and Poster Abstracts
Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Poster III
Hematology Disease Topics & Pathways:
Clinical Trials, Adults, Workforce, GVHD, Diseases, Immune Disorders, Patient-Reported Outcomes, Young Adults, Study Population
Monday, December 13, 2021, 6:00 PM-8:00 PM

Stephanie Lee, MD, MPH1, Franco Locatelli, MD, PhD2, Francis A. Ayuk, MD3*, Tsila Zuckerman, MD4, Kentaro Fukushima, MD5*, Juan Carlos Vallejo Llamas, MD6*, Joseph Pidala, MD7, Nada Hamad8, Ivan S. Moiseev, MD9, Francesca Bonifazi, MD10*, Shashikant Apte, MD, FRCPA11, Robert Zeiser, MD12, Valkal Bhatt, PharmD13*, Maanasa Gowda, PharmD14*, Jackie Han, MS14*, Tommaso Stefanelli, MD15*, Mike W. Zuurman, PhD15* and Takanori Teshima, M.D., Ph.D.16

1Fred Hutchinson Cancer Research Center, Seattle, WA
2Department of Hematology/Oncology, IRCCS Bambino Gesù Children’s Hospital, Sapienza, University of Rome, Rome, Italy
3Universitätsklinikum Hamburg Eppendorf, Hamburg, Germany
4Rambam Health Care Campus Technion, Haifa, Israel
5Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Suita-city,Osaka, Japan
6Hospital de Donostia, San Sebastián, Spain
7H. Lee Moffitt Cancer Center and Research Institute, Inc., Tampa, FL
8Department of Haematology, St Vincent's Hospital Sydney, Sydney, NSW, Australia
9St. Petersburg State Medical University n.a Pavlov, St. Petersburg, Russian Federation
10IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
11Sahyadri Specialty Hospital, Pune, India
12Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany
13Incyte Corporation, Wilmington, DE
14Novartis Pharmaceuticals Corporation, East Hanover, NJ
15Novartis Pharma AG, Basel, Switzerland
16Department of Hematology, Hokkaido University Hospital, Sapporo, Japan


Approximately 50% of patients (pts) who receive initial cGVHD therapy are steroid refractory or dependent (SR/D); standard second-line therapy has yet to be established. Quality of life (QOL) in these pts is poor and worsens with disease severity.

In the phase 3 REACH3 study in SR/D cGVHD (NCT03112603), RUX demonstrated superior efficacy compared with BAT, with a higher overall response rate at wk 24 (primary endpoint), longer failure-free survival, and a higher proportion of pts with a significant improvement in symptoms on the cGVHD-specific modified Lee Symptom Scale (mLSS; 24.2% vs 11.0% at wk 24; P=0.001) (Zeiser NEJM 2021).

Given the significant impact of symptoms on QOL, the collection of PROs is recommended by NIH consensus criteria, and assessing QOL via PRO measures specifically designed to capture cGVHD symptoms (ie, the mLSS) is important in evaluating treatment. We present an analysis of PROs in REACH3 and compare mLSS subscale results with objective organ responses (data cutoff: May 8, 2020).


Pts ≥12 years old with moderate or severe SR/D cGVHD were randomized (1:1) to RUX 10 mg twice daily or investigator-selected BAT (prespecified from 10 options). Randomized treatment was administered for ≥6 cycles (28 d/cycle) along with corticosteroids ± a calcineurin inhibitor. Addition or initiation of a new systemic agent for cGVHD was considered treatment failure.

PROs were collected at baseline and at 4-wk intervals through wk 24 or until treatment failure or discontinuation from the main study period. The rate of responders per improvement of ≥7 points from baseline in mLSS summary score (0 [no symptoms] to 100 [worst symptoms]) at wk 24 was a key secondary endpoint (alpha controlled). Additional endpoints were individual organ response and changes in other PROs (Functional Assessment of Cancer Therapy-Bone Marrow Transplantation [FACT-BMT], EQ-5D-5L, Patient Global Impression of Severity [PGIS], Patient Global Impression of Change [PGIC]). mLSS data at wk 24 were available for 55.8% of RUX pts (92/165) and 53.0% of BAT pts (87/164) (see Table for pts evaluable for other PROs).


A total of 329 pts received RUX (n=165) or BAT (n=164). Baseline characteristics, including symptom burden, were balanced between arms; 48% and 52% of pts had moderate or severe cGVHD, respectively. The baseline median summary mLSS score was 18.7 (RUX) vs 18.5 (BAT), indicating a moderate symptom burden.

More pts receiving RUX had an mLSS response at wk 24, at any time up to wk 24, and for ≥2 consecutive visits than those receiving BAT (Table). RUX was associated with a rapid and continued reduction in mean summary mLSS symptom score, whereas only an initial reduction at wk 4 was seen with BAT (Figure 1). In subset analysis, mLSS response was similar in RUX pts with moderate and severe cGVHD. Among pts achieving a complete or partial cGVHD response, those treated with RUX were more likely to have an mLSS response (RUX, 40.2%; BAT, 28.6%).

Response rates in mLSS subscales were higher with RUX vs BAT (odds ratio, >1.7; P<0.05, except lung). Greater mean reductions were observed with RUX vs BAT at wk 24 across all 7 mLSS subscales; improvements in organ-specific subscales corresponded with higher objective responses in the respective organ at wk 24 in both arms (Figure 2). As demonstrated by reductions on the Psych and Energy subscales, overall symptom burden not directly tied to organ responses was also better with RUX than BAT.

More pts receiving RUX than BAT reported “no symptoms” (28.6% vs 17.3%) according to PGIS and were “very much better” or “moderately better” (63.1% vs 39.5%) based on PGIC. RUX treatment also had a positive effect on non–cGVHD-specific PRO measures (EQ-5D-5L and FACT-BMT) at wk 24.


Compared with BAT, RUX resulted in more substantial improvement in PROs, with rapid, continued symptom improvement and benefits across mLSS subscales, indicating that RUX is superior to BAT not only in physician-assessed responses but also in terms of treating patients’ cGVHD symptoms. EQ-5D-5L and FACT-BMT scores were numerically higher with RUX than BAT, but the smaller changes suggest that these measures are too generic to fully capture the impact of cGVHD on QOL while confirming that multidimensional QOL was not reduced with RUX or BAT. Importantly, the pt experience of organ-specific symptom improvements was consistent with physician-assessed objective organ responses and both were greater with RUX.

Disclosures: Lee: Amgen: Research Funding; AstraZeneca: Research Funding; Incyte: Other: Membership on Steering Committee, Research Funding; Kadmon: Research Funding; Novartis: Research Funding; Pfizer: Consultancy, Research Funding; Syndax: Research Funding; Takeda: Research Funding; 4SC: Consultancy; EMD Serono: Consultancy, Research Funding; Genzyme: Consultancy; Merck Sharpe Dohme: Consultancy; Regeneron: Consultancy; Sanofi: Consultancy; BMS: Research Funding; Wolters Kluwer: Research Funding. Locatelli: Miltenyi: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Medac: Speakers Bureau; Jazz Pharamceutical: Speakers Bureau; Takeda: Speakers Bureau. Ayuk: Gilead: Honoraria; Mallinckrodt/Therakos: Honoraria, Research Funding; Takeda: Honoraria; Janssen: Honoraria; Celgene/BMS: Honoraria; Miltenyi Biomedicine: Honoraria; Novartis: Honoraria. Zuckerman: Gilead Sciences: Honoraria, Speakers Bureau; Novartis: Honoraria; AbbVie: Honoraria; BioSight Ltd: Honoraria; Orgenesis Inc.: Honoraria; Janssen: Honoraria; Cellect Biotechnology: Honoraria. Pidala: Pharmacyclics: Other: Clinical trial support, Research Funding; BMS: Other: Clinical trial support, Research Funding; Novartis: Other: Clinical trail support; Takeda: Other: Clinical trail support; Jannssen: Other: Clinical trial support; Johnson and Johnson: Other; AbbVie: Other; BMS: Other; Incyte: Consultancy; Regeneron: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Clinical trial support; CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Clinical trial support; Syndax: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Zeiser: Incyte, Mallinckrodt, Novartis: Honoraria, Speakers Bureau. Bhatt: Incyte: Current Employment. Gowda: Novartis: Current Employment. Han: Novartis: Current Employment. Stefanelli: Novartis: Current Employment, Current equity holder in publicly-traded company. Zuurman: Novartis: Current Employment. Teshima: Pfizer Inc.: Honoraria; Astellas Pharma Inc.: Research Funding; TEIJIN PHARMA Limited: Research Funding; Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees; Nippon Shinyaku Co., Ltd.: Research Funding; Bristol Myers Squibb: Honoraria; Gentium/Jazz Pharmaceuticals: Consultancy; Takeda Pharmaceutical Company: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis International AG: Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; CHUGAI PHARMACEUTICAL CO., LTD.: Research Funding; Kyowa Kirin Co.,Ltd.: Honoraria, Research Funding; Janssen Pharmaceutical K.K.: Other; Fuji pharma CO.,Ltd: Research Funding; Sanofi S.A.: Research Funding.

*signifies non-member of ASH