Navigating treatment sequencing of cGvHD: Real-world insights

Chronic graft-versus-host disease (cGvHD) can present with complications of variable severity affecting the skin, fascia, liver, gastrointestinal tract, eyes, mouth, and lungs.¹ Corticosteroids are the standard first-line treatment to treat these complications; however, subsequent treatment options after first-line therapy are unclear, due to high levels of uncontrolled immune response and treatment-induced toxicities.¹

Here, we summarize key data regarding real-world treatment sequencing at Canadian transplant centers, published by Kim et al.¹ in Transplantation Proceedings.

Study design¹

• A retrospective study of adult patients with cGvHD who received allogeneic hematopoietic stem cell transplantation greater than 18 months before data collection, from seven Canadian transplant centers, between September–November 2022.
• Data variables included patient characteristics, cGvHD complications information and management, and physician-reported healthcare resource utilization.
• Median values and interquartile ranges (IQR) were presented if data was not normally distributed.

Key findings¹

• In total, 77 patients with a median age of 52 were included in this study.
• Overall, 99% of patients received prednisone at some point during cGvHD treatment, as shown in Table 1. The median current dose was 27.5 mg/day (IQR, 8.5–35.0).

Table 1. Treatment received by patients with GvHD*

ECP, extracorporeal photopheresis; FAM, fluticasone azithromycin montelukast; GvHD, graft-versus-host disease; MMF, mycophenolate mofetil; MPA, mycophenolic acid. *Data from Dennis, et al.1
Treatments ever given (may be in combination)	All patients (n = 77)
Prednisone	76 (99%)
Ruxolitinib	41 (53%)
Cyclosporine	29 (38%)
Tacrolimus	22 (29%)
Mycophenolate (as MMF or MPA)	16 (22%)
ECP	13 (17%)
Imatinib	6 (8%)
Rituximab	5 (6%)
Ibrutinib	3 (4%)
Sirolimus	3 (4%)
Other (includes azathioprine, etanercept, FAM, and methotrexate)	12 (16%)

• First-line treatment of prednisone was paired with calcineurin inhibitors. 28% of patients received the cyclosporine combination and 16% received the tacrolimus combination.
• Ruxolitinib was the most common second-line therapy (37%), followed by mycophenolate mofetil/mycophenolic acid (17%).
• Among patients still on active systemic therapy (n = 59), prednisone and ruxolitinib were equally common at 47%.
• The most common third-line therapy was ruxolitinib (47%), again followed by mycophenolate mofetil/mycophenolic acid (17%).
• Overall, 80% of patients with cGvHD received ≤3 lines of therapy, and patients received ≥3 lines of therapy when lung complications (41%) or scleroderma (77%) were involved (Figure 1).

cGvHD, chronic graft-versus-host disease.
*Adapted from Dennis, et al.¹

• During the management of serious complications, follow-up appointments were required more frequently than in the absence of serious complications, 14 days (IQR 7–16) and 61 days (IQR 28–84), respectively.
  

Key learnings1

Treatment sequencing following challenges of first-line therapy is highly varied, reflecting a lack of effective treatment options and/or unequal access to treatments. Current treatment options do not adequately control cGvHD complications resulting in an increased strain on the healthcare system. New treatments with fewer serious adverse effects are needed to better manage cGvHD.