Improvements in Lymphoma Symptoms and Health-Related Quality of Life in Patients with Relapsed or Refractory Large B-Cell Lymphoma Treated with Subcutaneous Epcoritamab (EPCORE NHL-1)

Introduction: Epcoritamab is a first-in-class, subcutaneously administered, T-cell-engaging bispecific antibody that has shown good efficacy and safety in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who have received at least 2 prior systemic anti-lymphoma therapies, including those heavily pretreated and those with highly refractory disease (Thieblemont et al, EHA 2022). This analysis evaluated patient-reported outcomes (PROs) related to well-being and overall quality of life (QOL) based on changes in the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and EuroQol 5-Dimension-3L (EQ-5D-3L), including EuroQol visual analog scale (EQ-VAS) scores, among patients receiving epcoritamab for treatment of R/R LBCL in the EPCORE NHL-1 study (NCT03625037).

Methods: EPCORE NHL-1 was an open-label, phase 1/2 study that included a LBCL cohort. Adult patients were enrolled and treated with subcutaneously administered epcoritamab over 28-day cycles until disease progression (Thieblemont et al, EHA 2022). PROs were assessed using the FACT-Lym and EQ-5D-3L at baseline, on day 1 of odd-numbered cycles through cycle 9, and at the end of treatment (eg, due to disease progression, discontinuation due to adverse events). The compliance rate was the proportion of patients who provided any PRO response out of the patients still receiving treatment. Quantitative changes in the scores on the FACT-Lym and its subscales (ie, trial outcome index [TOI], Functional Assessment of Cancer Therapy-General [FACT-G] Total Score, FACT-Lym Total Score, FACT-Lym lymphoma subscale), EQ-5D-3L, and EQ-VAS were analyzed between baseline and follow-up, with higher scores reflecting better QOL and positive changes from baseline reflecting improvements in symptoms and overall health-related QOL. The magnitude of improvements was evaluated based on published ranges of minimum important differences (MIDs). In addition, a subgroup of patients participated in qualitative interviews to provide feedback on their experiences with epcoritamab treatment after completion of cycle 10 or upon early termination of treatment. Feedback from the patient interviews was qualitatively analyzed.

Results: A total of 157 patients with LBCL were enrolled in the trial. From baseline and through cycle 9 day 1, the compliance rates (n/N) were at least 81% (45/55 at cycle 9 day 1) for FACT-Lym and 90% (50/55 at cycle 9 day 1) for EQ-5D-3L, except for cycle 3 day 1, at which time compliance rates decreased to 36% (39/109) and 38% (41/109), respectively, due to PRO response collection being omitted for cycle 3 in a protocol version and subsequently reinstated upon protocol amendment. Mean (SD [MID]) changes between baseline and cycle 9 day 1 scores on the FACT-Lym and its subscales as well as the EQ-5D-3L and EQ-VAS were: TOI, 8.4 (15.17 [5.5-11.0]); FACT-G Total Score, 4.4 (15.16 [3.0-7.0]); FACT-Lym Total Score, 10.3 (20.23 [6.5-11.2]); lymphoma subscale, 5.9 (7.58 [2.9-5.4]); EQ-5D-3L, 0.049 (0.114 [0.08]); and EQ-VAS, 16.61 (22.83 [7.0]). Qualitative interviews (N=20 [n=10 completed cycle 10; n=4 early terminators]) showed that the majority of interviewed patients, including those terminating treatment early, who presented with symptoms at baseline (eg, fatigue, feeling/seeing the size of the tumor, body pain, weight loss, night sweats, fever, sleep difficulties, lack of appetite, breathlessness, nausea, weakness) reported improvements following treatment with epcoritamab (88.2%). Similarly, the majority of interviewed patients reported that epcoritamab had a positive impact on their daily activities (61.1%), and some reported a positive impact on their physical, emotional, and/or social functioning (38.9%-43.8%). Eighty percent of interviewed patients reported being either "very satisfied” or "satisfied” with treatment.

Conclusions: Patients treated with subcutaneous epcoritamab reported consistent and marked improvements in their symptoms and overall QOL through cycle 9 day 1. Improvements in the FACT-Lym subscales were within the published ranges of MIDs. Improvements in the lymphoma subscale and EQ-VAS exceeded the upper bounds of the published ranges of the MID. The quantitative improvements in PROs were also supported by the findings from the qualitative interviews in which most of the patients reported being "very satisfied” or "satisfied” with epcoritamab treatment.

Phillips:Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Research Funding; Kite/Gilead: Consultancy; Eli Lilly: Consultancy; Epizyme: Consultancy; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genmab: Consultancy; Incyte: Consultancy; Pharmacyclics/Janssen: Honoraria; TG Therapeutics: Consultancy; Curis: Consultancy; Celgene: Consultancy; Xencor: Consultancy; Lymphoma & Myeloma Connect: Honoraria; Beigene: Consultancy; Bayer: Consultancy, Research Funding; ADCT: Consultancy; Abbvie: Consultancy, Research Funding. Lugtenburg:Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genmab: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grants, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grants; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kalsekar:Genmab: Current Employment, Current equity holder in publicly-traded company. Mutebi:Genmab: Current Employment, Current equity holder in publicly-traded company. Wang:AbbVie: Current Employment, Current equity holder in publicly-traded company. Blaedel:Genmab: Current Employment, Current equity holder in publicly-traded company. Kosa:RTI Health Solutions: Current Employment; Genmab: Research Funding. Martin:RTI Health Solutions: Current Employment; Genmab: Research Funding. Sacchi:Genmab: Current Employment, Current equity holder in publicly-traded company. Thieblemont:Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses; Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses; Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses; Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses; Bayer: Honoraria; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding; Hospira: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding.