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798 Grndad and Disease Modifying Therapy (DMT): Shifts in Dmt Are Seen at the Adolescent/Young Adult Transition in Sickle Cell Disease in a Multi-Site Prospective Registry

Program: Oral and Poster Abstracts
Type: Oral
Session: 114. Sickle Cell Disease, Sickle Cell Trait and Other Hemoglobinopathies, Excluding Thalassemias: Clinical and Epidemiological: Advances in Clinical Care and Implementation
Hematology Disease Topics & Pathways:
Research, adult, Clinical Research, pediatric, Therapies, registries, Study Population, Human
Monday, December 11, 2023: 4:00 PM

Sophie Lanzkron1, Deepa Manwani, MD2, Julie Kanter, MD3, Arpan A Sinha, MD, MBBS4, Robin E. Miller, MD5, Robert Cronin, MD, MS6, Seethal A Jacob, MD, MS7, James Harper, MD8*, Alan Randall Anderson, MD9, Marsha Treadwell, PhD10, Amma T. Owusu-Ansah, MD11, Beng R. Fuh, MD12, Molly Mandernach13, Jahnavi Gollamudi, MD14, Suzanne L Saccente, MD15*, Stephanie A. Fritch Lilla, MD16, Melissa McNaull, MD17, Dana Marie LeBlanc, MD, MS18, Kay Linn Saving, MD19, Stephanie H. Guarino, MD20*, Marisol Betensky, MD21, Alice J. Cohen, MD22, Ashok B. Raj, MD23, Farzana A Sayani, MD24, Sanjay J. Shah, MBBS25, Shalu Narang, MD26, Bindu Kanathezhath Sathi, MD27*, John J Strouse, MD, PhD28, Trisha E. Wong, MD, MS29, Ofelia A. Alvarez, MD30, Srila Gopal, MD31, Jessica Liang32*, Daniel Semakula, PhD, MPH33*, Matthew Chang32*, Kenneth Rivlin, MD, PhD34*, Sana Saif Ur Rehman, MD35, Lisa M Shook, MA36, Melissa Frei-Jones, MD, MS37 and Jane A. Little, MD38

1Johns Hopkins Medical Institute, Baltimore, MD
2Department of Pediatric Hematology-Oncology, Albert Einstein College of Medicine, Bronx, NY
3Division of Hematology and Oncology, University of Alabama, Birmingham, AL
4University of Oklahoma, Oklahoma City, OK
5Nemours Center for Cancer and Blood Disorders, Nemours Children’s Health, Wilmington, DE
6Department of Internal Medicine, The Ohio State University, Columbus, OH
7Riley Hospital For Children, Indianapolis, IN
8University of Nebraska Medical Center, Omaha, NE
9PRISMA Health Comprehensive Sickle Cell Disease Program, University of South Carolina School of Medicine, Greenville, SC
10Department of Pediatrics, Division of Hematology, University of California San Francisco Benioff Children's Hospital, Oakland, CA
11University Hospitals, Cleveland, OH
12East Carolina University, Greenville, NC
13University of Florida, Gainesville, FL
14University of Cincinnati, Cincinnati, OH
15Arkansas Children's Hospital, Little Rock, AR
16Children's Minnesota, Minneapolis, MN
17Nationwide Children's Hospital, Jackson, MS
18Louisiana State University Health Science Center, New Orleans, LA
19University of Illinois College of Medicine - Peoria, Peoria, IL
20ChristianaCare, Wilmington, DE
21Johns Hopkins All Children's Hospital, Saint Petersburg, FL
22Newark Beth Israel Med. Ctr., Newark, NJ
23Norton Children's Hospital, University of Louisville, Louisville, KY
24The Trustees of The University of Pennsylvania, Philadelphia, PA
25Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, AZ
26Newark Beth Israel Medical Center, Newark, NJ
27Valley Children's Hospital, Madera, CA
28Department of Medicine, Division of Hematology, Duke University School of Medicine, Durham, NC
29Oregon Health & Science University, Portland, OH
30Department of Pediatrics, Division of Pediatric Hematology/Oncology, Univ. of Miami School of Med., Miami, FL
31University of California San Diego Health, San Diego, CA
32Johns Hopkins University, Baltimore, MD
33Johns Hopkins School of Medicine, Baltimore, MD
34NYC Health + Hospitals, Bronx, NY
35Washington University, Saint Louis, MO
36Cincinnati Childrens Hospital, Cincinnati, OH
37University of Texas Health Science Center at San Antonio, San Antonio, TX
38Division of Hematology and UNC Blood Research Center, University of North Carolina, Chapel Hill, NC

The ability to characterize the modern person living with SCD in the US has been limited by the lack of a well-curated longitudinal registry. The Globin Research Network for Data and Discovery (GRNDaD) registry aims to overcome this challenge by collecting data from the now 53 IRB-approved centers across the US in collaboration with the National Alliance of Sickle Cell Centers (NASCC) and the HRSA-funded Sickle Cell Disease Treatment Demonstration Project Grant. Here, we describe the use of disease-modifying therapy in (actively consented) adults and children with Hgb SS/ SB0 thalassemia (SCA) from 37 sites.

Methods: Each site consents subjects and enters extensive baseline data including SCD complications and labs, subjects also complete patient-reported outcomes (PROs)-both at baseline and annually. Each subject is expected to have an annual follow-up where data is extracted from the Electronic Health Record (EHR). All data is stored in REDCap and, for this abstract, data were extracted into R on all active subjects (data entry in the last two years) who have complete minimum data collected. Median values were compared using Mann-Whitney U tests. Disease-modifying therapy (DMT) in this study comprises hydroxyurea (HU), chronic red blood cell (RBC) transfusions, crizanlizumab, L-glutamine, and voxelotor.

Results: There are 2501 active patients in GRNDaD. Twenty-six percent of subjects are pediatric </= 18 years of age, 55.5% are female and 66.7% have HgbSS or HgbSB0 thalassemia (SCA). Here, we report data on people with SCA only, whose minimum data were complete (n=1272). Table 1 shows DMT by age. 187 (21%) adults and 31 (8.5%) children were not on DMT. Figure 2 is a box plot of the absolute neutrophil count (ANC) comparing adults and children who are and are not taking HU. Adults on HU had significantly lower ANCs than those not on HU (median = 4.4 (IQR: 3.07, 6.3) v 6.6 (IQR:4.07, 8.14), p<0.001) (Figure). Similar findings were observed for children ( median = 3.5 (IQR:2.5, 5.7) Vs 8.1 (5.8, 12.8) , p =0.04) Both children and adults on HU had higher MCVs than those not on HU (median for peds: 91.5 (IQR: 85.1, 98.75) v 86 (IQR: 83.3, 86.1), p=0.05, median for adults: 96.5 (IQR: 89, 107) v 90 (IQR: 86.1, 95.1), p<0.001). We compared hemoglobin for those on and off HU, and on and off voxelotor, excluding patients on chronic transfusion therapy. There was a statistically significant difference in hemoglobin when comparing on or off of HU (median 8.9 g/dl (IQR 7.95, 9.9) v 8.2 g/dl (IQR: 7.2, 9.7, p =0.047)). There were no statistically significant differences in hemoglobin when comparing subjects on or off of voxelotor (median = 8.4 g/dl (IQR: 7.5, 9.6) vs 7.9 (IQR: 7.4, 9.8), p =0.57). In the adults, there were statistically significantly more males than females on HU, but there were no differences seen in the pediatric cohort. Examining DMT by age group, chronic RBC transfusion use doubled from the 11-17 age group to the 18–29-year age group (12% to 25%) and HU use decreased (83%-59%) over this same period.

Limitations: This cohort may over-represent those on DMT as those enrolled in GRNDaD were more likely to have clinic visits.

Discussion: GRNDaD has doubled the number of sites consenting subjects and entering data over the last year. The number is expected to increase again in the next 12 months, as an additional 15 sites are already IRB-approved with a goal to include all SCD centers in NASCC. This cross-sectional description of the current population of people living with SCD and treated in NASCC-recognized SCD centers in the US shows that the majority of those with SCA are receiving DMT. There is a noticeable decrease in HU use during the transition period with an increase in the use of chronic transfusion therapy. Newer DMT has had limited uptake in this cohort. The next steps will be to provide longitudinal data on this population and examine associations of DMT and important clinical outcomes including PROs.

Disclosures: Lanzkron: Imara: Research Funding; Novartis: Research Funding; Global Blood Therapeutics: Research Funding; Takeda: Research Funding; CSL-Behring: Research Funding; HRSA: Research Funding; PCORI: Research Funding; MD CHRC: Research Funding; Bluebird Bio: Consultancy; Novo Nordisk: Consultancy; Magenta: Consultancy; Pfizer: Current equity holder in publicly-traded company; Teva: Current equity holder in publicly-traded company. Manwani: Novartis, Pfizer, Novo Nordisk, Editas, GBT: Consultancy. Kanter: Austin Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chiesi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bausch: Consultancy; Watkins, Lourie, Roll & Chance: Consultancy; Vertex: Consultancy; ECOR-1: Consultancy; Guidepoint Global: Honoraria; Fulcurm: Consultancy; Glycomimetics: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; BEAM: Consultancy, Research Funding; CDC: Research Funding; NHLBI: Research Funding; Bluebird Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; HRSA: Research Funding; National Alliance of Sickle Cell Centers: Other: President. Jacob: Global Blood Therapeutics: Other: Ad Hoc advisory Board Member - ended 2022. Anderson: Novartis Pharmaceuticals Corporation: Consultancy; Pfizer: Consultancy, Research Funding, Speakers Bureau; Vertex: Consultancy; Novo Nordisk: Consultancy. Treadwell: Wolters Kluwer Health: Patents & Royalties; Pfizer/Global Blood Therapeutics: Consultancy. Fuh: Novartis: Consultancy. Fritch Lilla: Chiesi: Membership on an entity's Board of Directors or advisory committees. Guarino: Novartis: Consultancy. Betensky: Janssen Pharmaceuticals: Consultancy, Honoraria. Raj: US WorldMeds: Consultancy; Jazz: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau. Sayani: Agios Pharmaceuticals: Research Funding. Sathi: Vertex Pharmaceuticals: Consultancy. Strouse: Agios, Takeda, Disc Medicine: Consultancy, Research Funding. Alvarez: Novartis: Consultancy; Global Blood Therapeutics: Consultancy. Gopal: Alexion: Speakers Bureau; bluebird bio: Honoraria. Little: Hemex: Patents & Royalties: Make no profit; Biochip Labs: Patents & Royalties: Make no profit; NASCC: Research Funding; NHLBI: Honoraria; USC: Research Funding; American Society of Hematology: Research Funding; GBT: Research Funding; bluebird bio: Consultancy; FORMA: Other: Adjudication committee for Hibiscus study; Novo Nordisk: Consultancy; Pfizer: Consultancy.

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