A discrete choice experiment (DCE) to determine preferences for relapsed-refractory follicular lymphoma (R-R FL) treatment attributes among patients and physicians in the USA

Abstract Background Follicular lymphoma (FL) is an indolent form of non-Hodgkin lymphoma. After initial treatment, patients often relapse or become refractory, subsequently undergoing multiple lines of therapy. While immuno-chemotherapy has been used to treat R-R FL, newer alternatives have emerged for later lines including bispecific (BiSP) antibodies, enhance of zeste homolog 2 (EZH2) inhibitors and chimeric antigen T-cell (CAR-T) therapies. We characterised patients' and physicians' preferences for R-R FL treatment attributes (linked to treatment modality) in an overall population, and in patient subgroups (second line vs third or later line [2L vs 3L+] and fit vs frail). Methods R-R FL patients (from USA; 18+ years) with ≥1 prior line of treatment were included. Eligible physicians (oncologists or hemato-oncologists) treated ≥3-5 FL patients per year depending on rural/urban location. A 25-minute online survey incorporated a DCE (alternative specific design). FL treatment attributes were defined through literature review and physician/patient input. Participants completed 12 choice tasks in which they selected their preferred alternative (oral, subcutaneous [SC], intravenous [IV] , CAR-T or none) based on varying levels of 8 attributes (frequency of treatment, duration of treatment, time for administration, intensity/setting of monitoring, duration of progression-free survival [PFS], risk of severe adverse events [AEs] requiring intervention [grade 3+], risk of cytokine release syndrome [CRS, any grade] and risk of nerve toxicity / immune effector associated neurotoxicity syndrome [ICANS; any grade]). Data were modelled using a mixed multinomial logit model with alternative specific parameters. Results We included 100 patients (54% female; mean±SD 64.3 years ±5.9; 62% frail; 63% 3L+) and 81 physicians (85.4% hemato-oncologists; 54.9% from teaching hospitals; mean±SD 19.1 ± 20.0 FL patients treated per month). In terms of relative attribute importance, AEs and PFS were most important to patients for all treatment alternatives, with some variation in ranking across modes of administration. The utility of oral treatment and CAR-T was more sensitive to these parameters than IV, indicating that preference for oral increases with more favorable AE (i.e., lower risk of grade 3+ AEs, CRS and nerve toxicity) and longer PFS. When PFS was defined as 24 months for all alternatives and AEs held equal, preference share was 32.4.% for IV (BiSP-like), 27.2% for oral (EZH2-like), 21.0% for SC (BiSP-like), 17.6% for CAR-T and 1.8% for no treatment (‘opt out‘)]. With PFS at 36 months, preference share was 24.4%, 34.0%, 17.4%, 23.5% and 0.7%, respectively. Physicians focused on PFS as the most important attribute for all alternatives, with the importance of AEs increasing when treating frailer patients. The DCE model allowed assessment of preference share between alternatives when attribute values were aligned to newer treatment profiles. For example, in the overall patient population, preference share was 43.0% for oral (EZH2-like), 15.6% for CAR-T, 13.9% for IV (BiSP-like), and 12.5% for SC (BiSP-like) (with 14.9% of patients choosing the ‘opt-out‘). In frailer patients, the percentage of patients preferring oral (EZH2-like) and IV (BiSP-like) was similar to the overall group. Amongst fit patients, there was around 40% uptake for oral (EZH2-like) and share for IV (BiSP-like) increased to 21.4%. A similar trend was observed for 3L+ vs 2L patients. For physicians, 39.9% considered oral (EZH2-like) for the overall population, 22.9% CAR-T, 18.1% SC (BiSP-like) and 15.4% IV (BiSP-like) (3.8% of physicians ‘opted-out‘). For frail patients, physician preference share for oral (EZH2-like) was 70.0%, but CAR-T was a preferred option for fit patients (72.3%). Conclusions Our results demonstrate potential differences in preferences for treatment alternatives in R-R FL between patients and physicians. Patient preference was dependent on PFS length and fewer AEs (particularly for oral). If AEs were similar, preference for IV and CAR-T increased based on PFS alone. Physicians focused more on PFS. Preference may also vary depending on patients' physical condition and line of therapy. Our data underline the importance of shared decision-making between physicians and patients, and the opportunity for physician-led education about the comparative safety and efficacy of different treatments. This may translate into improved patient adherence and outcomes.