(P 211) REAL-WORLD EXPERIENCE OF PATIENTS NEWLY INITIATED ON PEXIDARTINIB FOR TENOSYNOVIAL GIANT CELL TUMOR

Objective: Tenosynovial giant cell tumors (TGCT) are a family of neoplastic, inflammatory lesions that arise within the synovium and can be locally aggressive. Patients with TGCT frequently experience pain and joint swelling, as well as stiffness, reduced range of motion, and instability in affected joints. Disease progression can lead to additional complications, most commonly mobility impairment and joint deterioration. Pexidartinib (Turalio®), a CSF-1R antagonist, is the first and only systemic therapy approved by the FDA for the treatment of adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. The objective of this study was to assess symptom change over time among patients who were newly initiated on pexidartinib for TGCT in a real-world setting.

Methods: This was a longitudinal observational study based on surveys with TGCT patients who were newly initiated on pexidartinib in the real-world setting. The surveys were administered to adult patients enrolled in the post-market Risk Evaluation and Mitigation Strategy (REMS) program, and the participants completed patient-reported outcome (PRO) assessments electronically at baseline when initiating pexidartinib and were followed within 12 months. The surveys consisted of validated instruments that measured the following domains: (1) physical function of the upper/lower extremity by Patient-Reported Outcomes Measurement Information System physical function (PROMIS-PF); (2) joint stiffness by the one-item Worst Stiffness Numeric Rating Scale (NRS); (3) joint pain by the one-item Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale Score (NRS); (4) treatment satisfaction by the 14-item Treatment Satisfaction Questionnaire for Medication (TSQM); and (5) change in physical function and overall symptom since initiating pexidartinib by the Patient Global Impression of Change (PGIC). Random slope regression models were developed using time since first pexidartinib dose as an independent variable to describe rate of change in patient-reported outcome measures from baseline to last follow-up.

Results: The study enrollment started from April 1, 2022 (first patient enrolled) and ends on October 31, 2022 (last patient enrolled). There were eighty eligible patients who were newly initiated on pexidartinib invited to the surveys, and eleven patients completed the baseline survey and at least one follow-up survey within 12 months. Median (range) duration of follow-up was 8.2 (0.5-11.5) months, mean (SD) age at baseline was 42.2 (12.2) years, 54.5% (6/11) were female, and 45.4% (5/11) of tumors located at knees (Table 1). 72.7% (8/11) endorsed moderately high satisfaction with pexidartinib treatment (scored at least 70 out of 100 points on TSQM). Among eight participants providing responses for PGIC, 87.5% (7/8) reported “much improved” or “very much improved” in overall symptoms since initiation of pexidartinib (Table 2). The majority of patients reported reduction in stiffness (72.7%, 8/11) and pain (72.7%, 8/11) since initiation of pexidartinib (Figure 1). Two patients (Participant No. 2 and No. 11) who reported worsening of stiffness (+2 and +4 on NRS) also reported minimal worsening in physical function; however, both reported reduction in pain (−3 and −2 on NRS) and felt overall change in symptoms to be “Much improved” on PGIC (Figure 1, Table 2). The average rate of change (ARoC) (per year) derived from random slope regression models of the outcome measures revealed a statistically significant reduction in Worst Pain NRS (ARoC = −2.44, p-value = 0.03) during treatment with pexidartinib, though reduction in Worst Stiffness NRS (ARoC = −1.82, p-value = 0.20) and improvement in PROMIS-PF (ARoC = 6.33, p-value = 0.24) were not statistically significant.

Conclusion: TGCT is known to negatively impact the quality of life of working-age adults; however, most patients in this study reported improvements of symptoms that could be noticeable as early as a half-month following first dose of pexidartinib. Achieving clinically meaningful reduction in pain is considered a major driver of patients’ overall impression of change in disease status. Larger real-world studies about PROs of newly initiated pexidartinib patients should be evaluated.