A Healthcare Utilization Model Comparing Time Toxicity between Glofitamab and Epcoritamab

Background:

Bispecific antibodies (BsAbs), such as glofitamab (Glofit) and epcoritamab (Epcor), are approved treatment (tx) options for patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after ≥2 lines of therapy. While early data suggest similar efficacy and safety, frequency of administration and associated healthcare (HC) visits differ between the Glofit and Epcor tx regimens. Frequent visits to HC facilities and time spent coordinating care, known as “time toxicity”, is important for pts when making tx decisions (Gupta et al. JCO 2022). While time toxicity was studied in solid tumors (Gupta et al. JCO Oncol Pract 2023), no studies to date have quantified time toxicity in DLBCL in the context of BsAbs. We aimed to compare the time toxicity of Glofit vs Epcor tx based on schedules of administration, clinical evaluation, and estimated hospital days from BsAb registrational studies (Dickinson et al. NEJM 2022 [NCT03075696]; Thieblemont et al. JCO 2022 [NCT03625037]).

Methods:

A HC utilization model was developed to estimate HC visits associated with Glofit and Epcor in pts with R/R DLBCL. Publications on BsAb registrational studies, FDA prescribing information (PI), and study protocols were used to quantify HC visits. Time toxicity was defined as HC contact days, where clinic visits, infusions, procedures, bloodwork, and elective/unplanned hospital stays were considered all-day affairs; days without HC contact were considered home days. Overall survival (OS) was defined as HC contact days plus home days (Gupta et al. JCO 2022). HC contact days included: 1 day for screening; 1 day for each timepoint requiring clinic and/or tx visits; 1 day of inpatient cytokine release syndrome (CRS) monitoring; and 1 day for imaging scans to assess response. Hospital length of stay (LOS) for Grade 3/4 adverse events (AEs) was derived from the 2021 Healthcare Cost and Utilization Project National Inpatient Sample Database. HC contact days were measured from screening to end of tx and excluded subsequent tx or follow-up visits. It was assumed that tx administration schedules were based on PI and did not include tx modifications or off-protocol visits, and hospitalization was required for Grade 3/4 AEs (data obtained from PI). OS was measured as the restricted average days at 12 months, and a common OS curve was assumed (Mahmoudjafri et al. ASH 2023). Time horizons were 1 year and 2 years.

Results:

Over a 1-year time horizon, Glofit was associated with 30.9 HC contact days, including 1 day of screening, 1 day of pretreatment with obinutuzumab, 13 days of Glofit administration, 1 day for inpatient CRS monitoring (counted on the same day as the 2.5 mg dose), 5 separate days for vital signs/laboratory tests (Cycles [C] 1 and 2), and 4 separate days for imaging scans. Weighted average hospital LOS for Grade 3/4 AEs was 6.9 days. Common clinical Grade 3/4 AEs included infections (10.0%), febrile neutropenia (2.6%), and immune effector cell-associated neurotoxicity syndrome (ICANS; 3.0%). Grade 3/4 CRS occurred in 4.1% of pts.

Over a 1-year time horizon, Epcor was associated with 44.9 HC contact days, including 1 day of screening, 28 days of Epcor administration, 1 day for inpatient CRS monitoring (counted on the same day as the first full dose), 1 separate day for laboratory tests (C2), and 7 separate days for imaging scans. Weighted average hospital LOS for Grade 3/4 AEs was 7.9 days. Common clinical Grade 3/4 AEs included infections (14.0%), febrile neutropenia (2.5%), and ICANS (0.6%). Grade 3/4 CRS occurred in 2.5% of pts.

At a 1-year time horizon, estimated mean OS was 273 days for both Glofit and Epcor tx. Epcor was associated with fewer home days vs Glofit (228.1 days vs 242.1 days). Epcor was associated with an additional 14.0 HC contact days (44.9 days) vs Glofit (30.9 days). At a 2-year time horizon, continuous Epcor tx was associated with 29.0 additional HC contact days (59.9 days) vs fixed-duration Glofit (30.9 days).

Conclusions:

Epcor was associated with a greater time toxicity of approximately 2 weeks vs Glofit over a 1-year time horizon. As HC visits are increasingly recognized as all-day affairs, these findings can help pts, caregivers, and clinicians make decisions on different BsAbs by considering differences in time toxicity. Future studies using real-world patient-level data to model the time toxicities of different BsAbs and patient perspectives on the value of time toxicity in R/R DLBCL are needed.