TABLE 5.

Research recommendations regarding treatment.

Future research recommendations: treatment
ECP	⁃ Definition and prediction of treatment response ⁃ Consolidation of subgroup analyses to better define responder profiles ⁃ Harmonization of practices concerning the frequency and duration of ECP, including RCTs on continuation vs. discontinuation in stable patients under treatment ⁃ Evaluation of novel treatment targets, including the use of biomarkers, patient-reported outcome measures (e.g., quality of life and patient burden), acceptable and unacceptable side effects/adverse events, and central line requirement ⁃ Development of comparative cost-effectiveness studies ⁃ Beyond its role in CLAD management, more data is needed on the role of ECP in CLAD prevention
ATG	⁃ RCTs are warranted to better define efficacy and safety ⁃ Subgroup analyses to better define responder profiles, including different CLAD phenotypes ⁃ Determination of optimal dosing, treatment duration, and appropriate monitoring strategies ⁃ Data on high-risk groups, such as EBV-mismatched recipients at increased PTLD risk
Alemtuzumab	⁃ RCTs are necessary to better define efficacy and safety ⁃ Subgroup analyses to better define responder profiles, including different CLAD phenotypes and patients with DSAs ⁃ Determination of optimal dosing and scheduling of alemtuzumab ⁃ Better risk assessment for adverse events (e.g., PTLD risk in patients with EBV mismatch)
Antifibrotics	⁃ For the RAS phenotype, further investigation should be decided based on the results from the PIRCLAD study ⁃ Studies with other antifibrotics, such as nerandomilast
Other	⁃ Clinical trials with novel drugs in CLAD are an unmet need, and the Task Force recommends conducting well-designed RCTs (ideally multicenter RCTs) for CLAD treatment, in accordance with the recent ISHLT consensus statement on Lung Transplant Clinical Trials [105] ⁃ More data is needed on the efficacy and safety of JAK inhibitors in CLAD ⁃ More data is needed on the efficacy and safety of ROCK inhibitors in CLAD ⁃ More data is needed on the efficacy and safety of mesenchymal stem cells in CLAD ⁃ Data are required on other novel potential disease-modifying drugs

ATG, anti-thymocyte globulin; DSAs, donor-specific antibodies, ECP, extracorporeal photopheresis; JAK, Janus kinase; PTLD, post-transplant lymphoproliferative disease; RCT, randomized controlled trials; ROCK, Rho kinase.