Chair, Leslie Kean, MD, PhD, Corey Cutler, MD, MPH, FRCP(C), and Shernan Holtan, MD, prepared useful Practice Aids pertaining to graft-versus-host disease for this CME activity titled “Overcoming the Challenges of Acute and Chronic GVHD: The Integration of Novel Therapies Into Modern Management Protocols.” For the full presentation, downloadable Practice Aids, and complete CME information, and to apply for credit, please visit us at https://bit.ly/3qkmiiY. CME credit will be available until June 18, 2023.

1. Acute GVHD: The Current Shape of Management (Prophylaxis and Treatment) Includes the Use of
Calcineurin Inhibitors, Post-HCT Chemotherapy, Costimulation Inhibitors, Steroids, and JAK Inhibitors1,2
• Calcineurin inhibitor (tacrolimus ± sirolimus or cyclosporine) + methotrexate or mycophenolate mofetil
• Post-transplantation cyclophosphamide (PTCy)
• Abatacept is approved for prevention of acute GVHD in adults and pediatric patients ≥2 years of age
undergoing HCT from an unrelated donor
Calcineurin inhibitors are effective agents and have a lot of clinical experience
• They do not induce immune tolerance
• They are associated with adverse events such as hypertension and cardiovascular disease
PTCy is feasible and safe, and mismatched unrelated donor PTCy broadens access to transplant3
• In this setting, higher rates of GVHD and relapse in the myeloablative setting need to be addressed
Abatacept: calcineurin inhibitor/methotrexate + abatacept is the first FDA-approved GVHD prophylaxis strategy4
• Improved outcomes in both 8/8 and 7/8 unrelated donor HCT
• Efficacy of calcineurin inhibitor/methotrexate + abatacept is also seen in real-world settings
Prophylaxis
Take-Homes on Prophylaxis
Take-Homes and Management Principles Across the
Spectrum of GVHD Management
Full abbreviations, accreditation, and disclosure information available at PeerView.com/KPJ40

2. Acute GVHD: The Current Shape of Management (Prophylaxis and Treatment) Includes the Use of
Calcineurin Inhibitors, Post-HCT Chemotherapy, Costimulation Inhibitors, Steroids, and JAK Inhibitors1,2
First-line therapy
• Methylprednisolone (initiate for grade ≥2)
Steroid-refractory
• Ruxolitinib (adult and pediatric patients aged ≥12 years)
Basic treatment principles: Provide appropriate immunosuppression + supportive care; appropriate
immunosuppression is determined by severity of disease5,6
• Higher-risk disease may be signaled by high levels of amphiregulin
Initial steroid-based therapy is effective but be prepared to plan for subsequent/second-line therapy7
• ~50% of patients may need second-line therapy
Ruxolitinib is an approved second-line option in steroid-refractory acute GVHD
• Longer follow-up from the REACH2 study continues to show the benefits of ruxolitinib vs best available therapy
(FFS and EFS) in this setting8
Treatment
Take-Homes on Treatment
Take-Homes and Management Principles Across the
Spectrum of GVHD Management
Full abbreviations, accreditation, and disclosure information available at PeerView.com/KPJ40

3. In Chronic GVHD, Treatment Also Includes Multiple Modalities Such as Steroids
and Calcineurin, BTK, JAK, and ROCK inhibitors1,2
Treatment
Take-Homes on Treatment
First-line therapy
• Steroids and calcineurin inhibitors
• Mycophenolate mofetil in triple-agent regimens
Steroid-refractory
• Ibrutinib
• Ruxolitinib (adult and pediatric patients aged ≥12 years)
First-line therapy in chronic GVHD remains steroid and calcineurin-inhibitor based
• Emerging options (not yet approved) may include combinations of steroids with JAK or BTK inhibitors
Newer developments in second- and third-line therapy include the FDA approval of JAK inhibitors
(eg, ruxolitinib), BTK inhibitors (eg, ibrutinib), and ROCK inhibitors (eg, belumosudil)
• Based on current evidence, factors that may influence treatment selection in these settings include:
age of <18, a prior B-cell malignancy, presence of myelofibrosis/JAK2 disease, or lung involvement, including
advanced fibrosis8-11
Third-line therapy
• Belumosudil
1. Ruutu T et al. Bone Marrow Transplant. 2014;49:168-173. 2. Wolff D et al. Biol Blood Marrow Transplant. 2010;16:1611-1628. 3. Bolaños-Meade J et al. Lancet Haematol. 2019;6:e132-e143. 4. Watkins B et al. J Clin Oncol. 2021;39:1865-1877. 5. Holtan S et al. Blood Adv. 2018;2:1882-1888.
6. Levine JE et al. Lancet Haematol. 2015;2:e21-e29. 7. Jagasia M et al. Blood. 2020;135:1739-1749. 8. Zeiser R et al. N Engl J Med. 2020;382:1800-1810. 9. Chin K-K, Cutler C et al. Transplant Cell Ther. 2021;27:990.e1-990.e7. 10. Miklos D et al. EHA 2021. Oral Abstract Presentation.
11. Jagasia M et al. J Clin Oncol. 2021;39:1888-1898.
Take-Homes and Management Principles Across the
Spectrum of GVHD Management
Full abbreviations, accreditation, and disclosure information available at PeerView.com/KPJ40