(247) Impact of elexacaftor/tezacaftor/ivacaftor post-lung transplant on CFQ-R and SNOT-20 scores

Background: The impact of highly effective modulator therapy (HEMT) is not well studied in people who have undergone lung transplantation. While lung function changes are not expected from HEMT after a lung transplant, other benefits may present an advantage to patients struggling with non-pulmonary symptoms of CF. HEMT may improve chronic sinusitis, digestion, and weight gain, and reduce episodes of acute pancreatitis. Benefits of using HEMT after transplant must be weighed against risks including drug interactions with immunosuppression, adverse effects, and the unknown impact on the immune response.

Methods: This retrospective study of adults living with CF who were post lung transplantation used data collected from Cystic Fibrosis Questionnaire-Revised (CFQ-R) and Sino-Nasal Outcome Test (SNOT-20) symptom assessments. Patients were excluded from the study if symptom assessment scores were unavailable. The primary outcome of this study was to determine the impact of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on CFQ-R and SNOT-20 assessment scores in people who have undergone bilateral lung transplantation.

Results: This study included 21 patients who started ELX/TEZ/IVA after receiving a bilateral lung transplant. Data analysis included CFQ-R assessments from 8 patients and SNOT-20 assessments from 6 patients. The average age was 41.5 years (SD ±12.7 years) and patients were a median of 8 years post-transplant (IQR 6.6-9.9 years). All patients had at least one F508del mutation. The mean SNOT-20 score was 40.5 points (±31.3) pre-ELX/TEZ/IVA and 13.7 points (±12) post-ELX/TEZ/IVA (p=0.112). SNOT-20 scores for each individual patient are shown in Figure 1. There was no statistical difference seen in any of the CFQ-R domains with the addition of ELX/TEZ/IVA. The average CFQ-R respiratory domain score changed from 79.2 points (±11.8) pre-ELX/TEZ/IVA to 91.7 points (±9.4) post-ELX/TEZ/IVA (p=0.055). There was not a significant change in average weight (65.2 kg (±18.6) pre-ELX/TEZ/IVA and 64.1 kg (±21.8) post-ELX/TEZ/IVA, p=0.551) or ppFEV1 (67.6 (±18.8) pre-ELX/TEZ/IVA and 65.5 (±17.8) post-ELX/TEZ/IVA). At this time, all 8 patients continue ELX/TEZ/IVA, although one patient was changed from the standard dose to a reduced dose due to diarrhea. Of all 21 patients initiated on ELX/TEZ/IVA post-lung transplant, 15 patients remain on ELX/TEZ/IVA. One patient passed away due to complications from rejection. Two patients discontinued ELX/TEZ/IVA due to lack of perceived benefit. Three patients discontinued ELX/TEZ/IVA due to side effects outweighing benefit. Side effects observed included diarrhea, increased depression, constipation, headache, tinnitus, and rash. No adverse outcomes related to drug interactions between ELX/TEZ/IVA and immunosuppression were observed.

Conclusions: In this study of people with CF who were post-lung transplantation, ELX/TEZ/IVA did not change CFQ-R domain scores or SNOT-20 scores. SNOT-20 scores numerically improved for the majority of patients studied. Overall, ELX/TEZ/IVA was well tolerated and may improve certain non-pulmonary symptoms of CF. Larger studies are necessary to determine risk versus benefit profile of ELX/TEZ/IVA in people with CF who have received a lung transplant.

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