Current Treatment Landscape for Patients With Steroid-Refractory Chronic Graft-vs-Host Disease

The incidence of cGVHD has risen over the past decade, affecting 30% to 70% of patients following allogeneic stem cell transplantation.1,2 Although systemic steroids remain the cornerstone of first-line treatment, they are associated with significant toxicity and high failure rates, with few effective alternatives available until recently.5-7

Rates of chronic graft-vs-host disease (cGVHD) have risen over the past decade, affecting 30% to 70% of patients following allogeneic stem cell transplantation and significantly diminishing their quality of life (QoL).1,2 Based on the National Institutes of Health (NIH) criteria, the 2-year cumulative incidence rate of patients with cGVHD requiring systemic therapy is between 30% to 40%,3 although the incidence may be decreasing in recent years with better methods of prevention and other factors.4 When evaluating unmet needs in the treatment of steroid-refractory cGVHD (SR-cGVHD), Yi-Bin Chen, MD, Director of Hematopoietic Cell Transplant & Cell Therapy at Massachusetts General Hospital Cancer Center, noted that morbidity remains a significant concern. “A lot of patients suffer from the morbidity that is associated with cGVHD itself,” he said. “A majority of patients are on therapy for an extended period of time and experience the well-known complications of steroids, and most patients, even if responding to therapy, only achieve a partial response. [All of these patients] seek a better response and an improved overall quality of life.”

The primary goals of cGVHD treatment are to alleviate patient symptoms, prevent disease progression and irreversible damage, preserve organ function, and enhance patients’ overall survival and well-being.5 While systemic corticosteroids remain the mainstay of first-line therapy for cGVHD, they also carry a significant toxicity burden with high failure rates, with only 40% to 60% of patients responding.5-7

A majority of patients are on therapy for an extended period of time and experience the well-known complications of steroids…. [All of these patients] seek a better response and an improved overall quality of life. Yi-Bin Chen, MD

Pathogenesis of cGVHD

The pathogenesis of cGVHD is complex and mediated by multiple acute and chronic inflammatory pathways. The initial release of inflammatory cytokines and subsequent tissue injury activates donor T cells, initiating a cascade that eventually results in impaired regulatory B-cell and T-cell function, escape from immune regulation, and inadequate tissue repair. This cascade triggers macrophage activation, which activates fibroblasts, culminating in tissue fibrosis.8 While fibrosis serves as a wound-healing mechanism in some conditions, in cGVHD, it contributes to chronic disability often resulting in severe and potentially life-threatening complications and is the leading cause of toxicity and morbidity of cGVHD.8,9 Once fixed and nonprogressive, fibrosis often becomes resistant to treatment, underscoring the critical need for therapies that target multiple inflammatory pathways to be able to slow progression.

First-line treatment of cGVHD includes continuing or consideration of restarting original immunosuppressants or adding or initiating corticosteroids; unfortunately, only about half of patients respond.6,10 Additionally, approximately 40% to 50% of patients with cGVHD present with steroid-refractory disease.6 Considering the especially high morbidity associated with steroid-refractory disease, therapeutic strategies for patients with resistant disease are critical.6 “Most clinicians do not wait for steroid-refractoriness, as defined in clinical trials, to move on to second-line therapy,” Dr. Chen said, noting that the rationale for doing so also varies. “Considerations may include the desire to augment a partial response to steroids, lack of response to steroids, toxicities of steroids (or the fear of toxicities in patients with comorbidities that may be exacerbated by steroids), and the ability to more rapidly taper steroids,” he said. Novel therapeutic agents, such as Bruton’s tyrosine kinase (BTK), Rho-associated coiled-coil–containing protein kinase (ROCK), Janus associated kinases (JAK), and colony stimulating factor-1 receptor (CSF-1R) inhibitors, aim to improve outcomes of SR-cGVHD.11

Treatment Options for SR-cGVHD

The current treatment landscape for SR-cGVHD includes a range of therapies, four of which are approved for use by the U.S. Food & Drug Administration (FDA): ibrutinib, ruxolitinib, belumosudil, and axatilimab (Figure 1). The choice of treatment after corticosteroid failure varies in clinical practice, underscoring the importance of understanding the complex immunologic and inflammatory pathways and the differences between pharmacologic agents to optimize cGVHD therapy.1 Currently, ibrutinib and ruxolitinib are approved by the FDA for use in the second-line setting and beyond, while belumosudil and axatilimab are approved in the third-line setting. In lieu of strong guideline-driven approaches and head-to-head comparisons for selection of optimal agents for SR-cGVHD, therapy is often chosen based on physician experience and patient-specific factors.8 Chronic GVHD continues to pose a significant clinical challenge, highlighting the need for more effective therapies with fewer side effects than corticosteroids.

Table 1. FDA-Approved Therapies for SR-cGVHD

Abbreviations: BTK = Bruton’s tyrosine kinase; CSF-1R = colony stimulating factor-1 receptor; FDA = U.S. Food and Drug Administration; SR-cGVHD = steroid-refractory chronic graft-vs-host-disease; JAK = Janus associated kinase; ROCK2 = Rho-associated coiled-coil containing protein kinase 2.

Ibrutinib

Ibrutinib is a potent, irreversible BTK inhibitor.12 The BTK pathway regulates critical intracellular signaling pathways essential for B-cell proliferation and survival as well as inhibits interleukin-2 (IL-2)-inducible T-cell kinase, which plays a role in T-cell activation.12,13

In the initial phase I/IIb trial of 42 patients with cGVHD refractory to at least one prior therapy, participants received 420 mg of ibrutinib daily until cGVHD progression. At a median follow-up of 13.9 months, the overall response rate (ORR) was 67%, increasing to 69% at 26 months, with 31% of the patients achieving a complete response and 38% achieving a partial response.12 Additionally, 64% of patients were able to reduce their corticosteroid dose to less than 0.15 mg/kg/d, and 19% of patients discontinued corticosteroids entirely.14 Ibrutinib was approved for the treatment of adults with cGVHD after failure of one or more systemic therapies in 2017, with approval expanded to pediatric patients aged ≥ 1 year in 2022.15 The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) include ibrutinib as an NCCN category 2A treatment option for SR-cGVHD.6

Ruxolitinib

JAKs play a critical role in mediating the signaling of cytokines and growth factors that regulate hematopoiesis and immune system function.16 By preventing the recruitment of signal transducers and activators of transcription (STAT) to cytokine receptors, JAKs help modulate inflammation and tissue damage in cGVHD.11 Ruxolitinib inhibits JAK1 and JAK2, in turn blocking the JAK-STAT pathway involved in GVHD pathogenesis.16

REACH3 was a phase III clinical trial which enrolled 329 patients 12 years of age or older with moderate or severe steroid-refractory or steroid-dependent cGVHD. Patients received ruxolitinib at 10 mg orally twice daily or best available therapy (BAT). The overall response rate at week 24 was higher with ruxolitinib 49.7% vs 25.6% with BAT with an odds ratio of 2.99 (95% CI = 1.86–4.8) and a risk ratio of 1.93 (95% CI = 1.44–2.6; P < .001). A response on the modified Lee Symptom Scale was observed in 24.2% of patients treated, compared to 11% of patients receiving BAT (P = .001). The median duration of treatment was 6.4 months (range = 0.2–6.4 months) while the median duration of response had not been reached among patients who maintained their response through week 24. The median time from first response to either death or initiation of new systemic therapies for cGVHD was over 18.6 months with ruxolitinib, which was significantly longer than the 5.7 months observed with BAT (hazard ratio = 0.37; P < .001).17 The results of the REACH3 trial prompted the FDA to approve ruxolitinib at a dose of 10 mg orally twice daily for the treatment of cGVHD following the failure of at least one prior line of systemic therapy.8,16 A recent retrospective analysis of 48 patients further validated the safety and efficacy of ruxolitinib in a real-world setting, consistent with the findings of REACH3. At 6 months, the ORR was 33%, with a failure-free survival rate of 58%.18 The NCCN Guidelines® recommend ruxolitinib as a category 1 option for the treatment of SR-cGVHD.6

Belumosudil

ROCK plays an integral part in profibrotic signaling and processing.8 Belumosudil, a selective ROCK1 and ROCK2 inhibitor, disrupts profibrotic signaling and reduces the activity of proinflammatory Th17 cells through STAT3 downregulation.19 Belumosudil also enhances the activity of regulatory T cells (Tregs) through upregulation of STAT5 phosphorylation, thereby restoring immune balance.19

The phase II ROCKstar clinical trial enrolled 132 patients 12 years of age or older who had previously received at least two lines of systemic therapy.20 Belumosudil was administered at two dose levels of 200 mg daily or 200 mg twice daily. The primary endpoint, ORR, in the 200-mg belumosudil daily cohort was 74% (95% confidence interval [CI] = 62–84). The overall median time to response was 5 weeks (range = 4–66). Median duration of treatment was 10 months (range = 0.4–22) with a median duration of response lasting 54 weeks.20 Notably, 59% of patients maintained a response for ≥ 20 weeks with 65% of the patients being able to decrease their systemic corticosteroid dose.20 The efficacy demonstrated in ROCKstar, including among patients who were previously treated with ibrutinib or ruxolitinib, led to the FDA approval of belumosudil at 200 mg orally daily for the treatment of cGVHD after failure of at least two prior lines of systemic therapy.19 Recently, an open-label study performed in 21 patients in Japan showed similar outcomes with no new safety concerns.21 The NCCN Guidelines include belumosudil as a category 2A treatment option for SR-cGVHD.6

Axatilimab

CSF-1 and CSF-1R signaling is critical in the development, maintenance, and proliferation of macrophage lineage cells. This signaling pathway regulates inflammatory responses, tissue injury, and immune function.11 Axatilimab is a humanized IgG4 monoclonal antibody targeting CSF-1R expressed on the surface of monocytes and macrophages, leading to impaired signaling and subsequent decreased inflammation, tissue injury and fibrosis.11,22

The phase II AGAVE-201 trial evaluated axatilimab in 239 patients with recurrent or refractory cGVHD. Axatilimab was administered as an infusion across three dose levels with different frequencies. The primary endpoint, defined as an overall response (complete or partial), was achieved in patients at all dose levels, including the 0.3 mg/kg (given every 2 weeks) cohort. Notably, the highest ORR of 74% (95% CI = 63–83) was observed at the 0.3 mg/kg dose. A clinically meaningful reduction in cGVHD symptoms of more than 5 points on the modified Lee Symptom Scale was reported in 60% of the patients. The time to response was relatively long, with a median of 1.7 months (range = 0.9–8.1 months).24 The median duration of response was not reached at any dose level, with response maintained for 12 months or longer in 60% (95% CI = 43–74) of patients receiving the 0.3 mg/kg dose. The findings of AGAVE-201 resulted in FDA approval of axatilimab in August 2024 for the treatment of adult and pediatric patients weighing 40 kg or more with cGVHD that has persisted or recurred following failure of at least two prior systemic therapies.22 The recommended dose of axatilimab is 0.3 mg/kg IV every 2 weeks, not to exceed 35 mg, administered intravenously over 30 minutes every 14 days.22 The NCCN Guidelines include axatilimab as a category 2A treatment option for SR-cGVHD.6

Safety

Awareness of adverse events (AEs) is critical when choosing an agent for the treatment of SR-cGVHD based on the drug’s toxicity profile and the patient’s comorbidities. The most common treatment-related AEs (outside of laboratory abnormalities) for FDA-approved agents utilized in the treatment of SR-cGVHD are summarized in Figure 1.

Figure 1. Adverse Event Profiles of FDA-Approved Therapies for SR-cGVHD*

*Nonlaboratory, all grades, incidence rate ≥ 20%.
FDA = U.S. Food and Drug Administration; SR-cGVHD = steroid-refractory chronic graft-vs-host disease.

The most common AEs from treatment with ibrutinib that are grade 3 or higher include pneumonia (14%), fatigue (12%), and diarrhea (10%). Ibrutinib should be used with caution in patients with a history of cardiac arrhythmias, due to an increased risk of atrial fibrillation and atrial flutter (3.7%). Additionally, patients on concomitant anticoagulation or antiplatelet therapy are at an increased risk of bleeding and should discontinue ibrutinib therapy for 3 to 7 days before and after surgical procedures.15 Of note, while the initial trial that led to the FDA-approval of ibrutinib for cGVHD observed a 33% discontinuation rate due to AEs and two treatment-related deaths, in the 1-year follow-up, 43% of patients had discontinued treatment due to AEs and no new fatal AEs were observed.12,14

In the REACH3 study, nearly all patients in the ruxolitinib cohort (97.6%) experienced at least one nonlaboratory AE.18 A significant proportion of the patients (57%) experienced an AE of grade 3 or higher. The most frequent grade 3 or higher AE associated with ruxolitinib was infection (specific pathogen unspecified), occurring in 15% of patients.16 However, when using a grading system described by Cordonnier et al, the incidence of grade 3 or higher infections was even greater, at 19.4% with ruxolitinib, compared to 18.4% with BAT.17,23 Discontinuation due to AEs occurred in 16.4% of patients, with seven reported fatalities (4.2%) attributed to ruxolitinib.17 A recent analysis of real-world experience with ruxolitinib in the treatment of cGVHD confirmed similar AE trends. Infectious AEs of any grade were reported in 60% of patients, with 21% experiencing significant grade 3 or higher infections.18

Daily dosing of belumosudil, as observed in the ROCKstar study, revealed that in the 200-mg daily cohort most patients (99%) experienced at least one AE.20 Notably, more than half of the patients (56%) experienced an AE of grade 3 or higher, with the most common being infection without a specified pathogen, seen in 16% of patients.19,20 Although eight deaths (12%) were reported in the clinical trial, six of these occurred during long-term follow-up, more than 28 days after the last dose of belumosudil. Discontinuation due to AEs occurred in 12% of patients.20

The most common AEs, observed in the AGAVE-201 trial of axatilimab, were dose-dependent, transient laboratory abnormalities associated with CSF-1R blockade. In the 0.3-mg/kg cohort, most patients (96%) experienced at least one AE.24 The most common grade 3 or higher events observed in 49% of patients treated with axatilimab were viral infections (15%) and infections without a specified pathogen (14%).22,24 AEs leading to discontinuation of axatilimab occurred in 6% of the patients in the 0.3-mg dose group. One fatality (1%) was reported.24

Challenges in cGVHD: A Focus on Fibrosis Prevention

A primary goal of cGVHD treatment is to prevent progression to moderate or severe disease, as advanced cGVHD often results in irreversible fibrosis, affecting multiple organs.7,25

Platelet-derived growth factor receptor (PDGFR) drives cell proliferation and fibroblast migration while transforming growth factor beta (TGF-β) regulates extracellular matrix production and promotes the transformation of fibroblasts into myofibroblasts.26 In combination, both pathways lead to excessive protein deposition and subsequent fibrosis. PDGFR and TGF-β are expressed in differing concentrations across cell types, leading to variable levels of fibrosis among organs.27 Imatinib was one of the first agents investigated in the treatment of cGVHD based on its antifibrinolytic activity through targeting PDGFR and TGF-β pathways, although significant clinical improvement was fleeting.

The pathogenesis of cGVHD is further characterized by an imbalance between T helper 17 and T follicular helper (Th17/Tfh) effector cells as well as regulatory T-cells (Tregs). The ROCK2 isoform of the protein kinase stimulates proinflammatory Th17 cell response, upregulating the cellular process of fibrosis. Belumosudil inhibits ROCK2, shifting the Th17/Tfh balance in favor of Tregs and restoring immune homeostasis. It also downregulates TGF-β and the expression of profibrotic genes.28 This targeted action against the ROCK2 isoform helps mitigate fibrosis development, offering therapeutic benefits for patients with cGVHD and underlying fibrosis.

Ruxolitinib primarily targets B- and T-cell function, rather than pathways involved in fibrosis. In a recent phase II trial of 47 patients with sclerotic cGVHD affecting the skin and/or joints that was refractory to corticosteroids and at least one additional line of systemic therapy, notable responses were observed after 11 months of treatment with ruxolitinib. At 6 months, the partial response was 49% (95% CI = 34–64), with the duration of skin/joint response reaching 77% (95% CI = 48–91) at 12 months. The overall partial response rate for cGVHD was 47% (95% CI = 32–61).29 These findings suggest that some patients, particularly those with underlying sclerosis, may require prolonged therapy with ruxolitinib prior to seeing a pronounced benefit.

CSF1 is an endogenous ligand that activates CSF-1R and downstream signaling pathways, including JAK-STAT, mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), which play a significant role in fibrosis.30 Inhibition of CSF-1R signaling reduces immune system responses and inflammation, effectively mitigating cGVHD-associated cutaneous and pulmonary fibrosis.31 Axatilimab’s targeted blockade of CSF-1R and its subsequent downregulation of macrophage-induced inflammation and fibrosis highlight its efficacy in patients with cGVHD and underlying fibrosis.32 In the AGAVE-201 trial, among the 43% of patients with nonmovable sclerotic skin changes, 44.2% experienced improvement with axatilimab at dose of 0.3 mg/kg every 14 days, and 66% reported a reduction in skin tightening.24

What we need in the long run are biomarkers or noninvasive tests that can identify which inflammatory or immunologic pathways are active in each individual patient with cGVHD. This would allow clinicians to better predict how an individual patient will respond to a specific agent, allowing us to tailor therapy more effectively. Yi-Bin Chen, MD

Current therapies for SR-cGVHD employ diverse mechanisms of action and target different pathways to modulate fibrosis progression. However, further research is needed to identify the most effective strategies, in hopes of potentially reducing the impact of SR-cGVHD on patients' lives and improving both QoL and overall outcomes. In contemplating the future of therapy, Dr. Chen reflected, “What we need in the long run are biomarkers or noninvasive tests that can identify which inflammatory or immunologic pathways (eg, B cells, macrophages, ROCK2, JAK, or a mix) are active in each individual patient with cGVHD. This would allow clinicians to better predict how an individual patient will respond to a specific agent, allowing us to tailor therapy more effectively.”

Considerations in Treatment Selection for SR-cGVHD

Clinical trial data directly comparing agents used in second- and third-line treatment of cGVHD remain limited. In the absence of robust direct comparison study data, clinicians must rely on professional judgment, examining a range of factors in addition to safety and efficacy when determining the most appropriate agent for the treatment of SR-cGVHD. These factors include patient and disease characteristics, properties of the therapeutic agents, institutional and professional practices, and social determinants (Figure 2).6

Figure 2. Factors to Consider When Selecting an Agent for the Treatment of SR-cGVHD

Medication

  • Route of administration
  • Adverse event profile
  • Drug-drug interactions
  • Synergy with other agents
  • Ability to downregulate fibrotic pathways

Health-Care Provider

  • Clinician experience
  • Institutional preferences

Disease

  • Organ involvement
  • cGVHD grade
  • Effects of prior treatment

Patient

  • Patient tolerability
  • Convenience/accessibility
  • Financial implications
SR-cGVHD = steroid-refractory chronic graft-vs-host disease

“Provider experience is very powerful and, even though there is recency bias, it guides the treatment approach,” Dr. Chen noted. “In addition to the physician’s familiarity with the drugs, [factors such as] access to therapy, as well as payor coverage, influence treatment selection.”

Dr. Chen cautioned against basing treatment decisions on the clinical manifestation of cGVHD, such as scleroderma or bronchiolitis obliterans. “These clinical manifestations are the result of a convergence of multiple immunologic or inflammatory pathways,” he noted. “There is no evidence that these new therapies are organ-specific, but rather pathway-specific.”

Provider experience is very powerful and … guides the treatment approach. Yi-Bin Chen, MD

Conclusion

SR-cGVHD is a multifaceted complication of allogeneic hematopoietic stem cell transplantation for which treatment strategies remain to be fully optimized. With four new agents approved in recent years, treatment selection should consider patient comorbidities, prioritize a tolerable side effect profile, and attempt to minimize the impact of SR-cGVHD on QoL. Due to the significant morbidity associated with fibrosis in cGVHD, considerable efforts are underway to develop strategies and therapies aimed at slowing its onset and progression. Agents such as ibrutinib, ruxolitinib, belumosudil, and axatilimab offer effective treatment options for managing SR-cGVHD, while mitigating fibrotic pathways. Dr. Chen emphasized that, “Even though we are blessed to have several more options to use for our patients and this has definitely improved outcomes, we need more data on how to sequence therapies, how to use them in combination, and how to transition between agents.” Optimal therapy selection for SR-cGVHD should consider efficacy, toxicity profiles, and the ability to slow disease progression, ensuring a tailored approach to each patient’s needs.

Disclosure

Dr. Chen reported a leadership role with ImmunoFree; stock and other ownership interests with ImmunoFree; and consulting or advisory roles with Incyte, Novo Nordisk, Editas Medicine, Alexion Pharmaceuticals, Astellas Pharma, Takeda, Pharmacosmos, and Vor Biopharma.

References

  1. Wolff D, Fatobene G, Rocha V, et al: Steroid-refractory chronic graft-versus-host disease: Treatment options and patient management. Bone Marrow Transplant 56:2079-2087, 2021.
  2. Pidala J, Kurland B, Chai X, et al: Patient-reported quality of life is associated with severity of chronic graft-versus-host disease as measured by NIH criteria: Report on baseline data from the Chronic GVHD Consortium. Blood 117:4651-4657, 2011.
  3. Flowers ME, Martin PJ: How we treat chronic graft-versus-host disease. Blood 125:606-615, 2015.
  4. Carpenter PA, Gooley TA, Boiko J, et al: Decreasing chronic graft-versus-host disease rates in all populations. Blood Adv 8:5829-5837, 2024.
  5. Olivieri A, Mancini G: Current approaches for the prevention and treatment of acute and chronic GVHD. Cells 13:1524, 2024. 
  6. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Hematopoietic Cell Transplantation V.1.2025. National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed February 28, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  7. Zeiser R, Lee SJ: Three US Food and Drug Administration-approved therapies for chronic GVHD. Blood 139:1642-1645, 2022. 
  8. Malard F, Mohty M: Updates in chronic graft-versus-host disease management. Am J Hematol 98:1637-1644, 2023.
  9. Socié G: Treating chronic GVHD-induced fibrosis? Blood 131:1396-1397, 2018.
  10. Wolff D, Schleuning M, von Harsdorf S, et al: Consensus conference on clinical practice in chronic GVHD: Second-line treatment of chronic graft-versus-host disease. Biol Blood Marrow Transplant 17:1-17, 2011.
  11. Amanam I, Otoukesh S, Al Malki MM, et al: Chronic GVHD: Review advances in prevention, novel endpoints, and targeted strategies. Hematology Am Soc Hematol Educ Program 2023:164-170, 2023.
  12. Miklos D, Cutler CS, Arora M, et al: Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood 130:2243-2250, 2017.
  13. Garg N, Padron EJ, Rammohan KW, et al: Bruton's tyrosine kinase inhibitors: The next frontier of B-cell-targeted therapies for cancer, autoimmune disorders, and multiple sclerosis. J Clin Med 11:6139, 2022.
  14. Waller EK, Miklos D, Cutler C, et al: Ibrutinib for chronic graft-versus-host disease after failure of prior therapy: 1-year update of a phase 1b/2 study. Biol Blood Marrow Transplant 25:2002-2007, 2019. 
  15. IMBRUVICA® (ibrutinib) prescribing information. Janssen Biotech, Inc, 2024. Available at: https://www.rxabbvie.com/pdf/imbruvica_pi.pdf. Accessed November 26, 2024.
  16. JAKAFI® (ruxolitinib) prescribing information. Incyte Corporation, 2023. Available at: https://www.jakafi.com/jakafi-prescribing-information. Accessed November 18, 2024.
  17. Zeiser R, Polverelli N, Ram R, et al: Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease. N Engl J Med 385:228-238, 2021. 
  18. Denk A, Mittermaier C, Weber D, et al: Efficacy and safety of ruxolitinib in the treatment of chronic graft-versus-host disease: A retrospective analysis. Ann Hematol 103:3755-3764, 2024.
  19. REZUROCK® (belumosudil) prescribing information. Kadmon Pharmaceuticals, LLC, 2024. Available at: https://products.sanofi.us/rezurock/rezurock.pdf. Accessed November 18, 2024.
  20. Cutler C, Lee SJ, Arai S, et al: Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: The ROCKstar study. Blood 138:2278-2289, 2021.
  21. Inamoto Y, Kato K, Kawakita T, et al: An open-label study of belumosudil, a selective ROCK2 inhibitor, as second or subsequent line of therapy for steroid-dependent/steroid-resistant chronic GVHD. Am J Hematol 99:1917-1926, 2024. 
  22. NIKTIVMO™ (axatilimab-csfr) prescribing information. Incyte Corporation, 2024. Available at: https://www.niktimvo.com/pdf/prescribing-information.pdf. Accessed November 17, 2024.
  23. Cordonnier C, Maury S, Ribaud P, et al: A grading system based on severity of infection to predict mortality in allogeneic stem cell transplant recipients. Transplantation 82:86-92, 2006.
  24. Wolff D, Cutler C, Lee SJ, et al; AGAVE-201 Investigators: Axatilimab in recurrent or refractory chronic graft-versus-host disease. N Engl J Med 391:1002-1014, 2024. 
  25. Cooke KR, Luznik L, Sarantopoulos S, et al: The biology of chronic graft-versus-host disease: a task force report from the National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease. Biol Blood Marrow Transplant 23:211-234, 2017.
  26. Biernacka A, Dobaczewski M, Frangogiannis NG: TGF-β signaling in fibrosis. Growth Factors 29:196-202, 2011.
  27. Pandey P, Khan F, Upadhyay TK, et al: New insights about the PDGF/PDGFR signaling pathway as a promising target to develop cancer therapeutic strategies. Biomed Pharmacother 161:114491, 2023.
  28. Zanin-Zhorov A, Blazar BR: ROCK2, a critical regulator of immune modulation and fibrosis has emerged as a therapeutic target in chronic graft-versus-host disease. Clin Immunol 230:108823, 2021. 
  29. Bhatt VR, Shostrom VK, Choe HK, et al: A multicenter phase II trial of ruxolitinib for treatment of corticosteroid refractory sclerotic chronic graft-versus-host disease. J Clin Oncol 42:3977-3985, 2024.
  30. Xiang C, Li H, Tang W: Targeting CSF-1R represents an effective strategy in modulating inflammatory diseases. Pharmacol Res 187:106566, 2023.
  31. Alexander KA, Flynn R, Lineburg KE, et al: CSF-1-dependant donor-derived macrophages mediate chronic graft-versus-host disease. J Clin Invest 124:4266-4280, 2014.
  32. Kitko CL, Arora M, DeFilipp Z, et al: Axatilimab for chronic graft-versus-host disease after failure of at least two prior systemic therapies: Results of a phase I/II study. J Clin Oncol 41:1864-1875, 2022.

Disclaimer

Sponsored content is not written by and does not necessarily reflect the views of ASCO or The ASCO Post editorial staff. It is authored by Harborside Studio writers or independent medical writers approved by Harborside Studio. Harborside Studio's sponsored content is held to editorial standards expected in The ASCO Post with the intent to provide valuable information to The ASCO Post readers. Interviewed experts receive no remuneration for their comments. The mention of any company, product, service, or therapy does not constitute an endorsement of any kind by ASCO. ASCO assumes no responsibility for any injury or damage arising out of or related to use of the sponsored content or any errors or omissions. Incyte provided early input on the topic and reviewed the final content for scientific accuracy. This content was produced with funding support from Incyte and is intended for U.S. health-care professionals only.