Patient-reported long-term quality of life after tisagenlecleucel in relapsed/refractory diffuse large B-cell lymphoma

Abstract

The JULIET phase 2 trial evaluated a single infusion of tisagenlecleucel in adult patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL). The objective of the current analysis was to evaluate patient-reported health-related quality of life (HRQoL) with a median follow-up of 19.3 months among patients infused with a single dose of tisagenlecleucel. Patients enrolled were ≥18 years of age with r/r DLBCL after ≥2 lines of therapy and had either undergone a failed autologous stem cell transplant or were ineligible for the procedure. Two validated HRQoL instruments, Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and Short Form-36 (SF-36) Health Survey, were used to measure HRQoL at baseline and months 3, 6, 12, and 18. At data cutoff (21 May 2018), 115 patients had received tisagenlecleucel infusion. Among the 99 patients evaluated, overall response rate was 54%, and 40% of patients achieved complete response (CR). Initially, 108 patients completed the HRQoL assessments at baseline, including 57 patients who eventually achieved CR or partial response (PR). Further, 30 and 21 patients in clinical response who completed assessments at baseline also completed assessments at months 12 and 18, respectively. Patients who achieved CR or PR sustained HRQoL improvement in all FACT scores at all time points. SF-36 instruments showed improvement above the minimal clinically important differences on 5 of 8 subscales. Long-term follow-up in the phase 2 JULIET study demonstrated that patients with r/r DLBCL who respond to tisagenlecleucel therapy had sustained, clinically meaningful improvements in HRQoL. This trial was registered at www.clinicaltrials.gov as #NCT02445248.

Conflict of interest statement

Conflict-of-interest disclosure: R.T.M. has received honoraria from, held membership on the board of directors or advisory committees for, and received research funding from Novartis; provided consultancy to and received honoraria from Incyte and Juno; received honoraria from Kite and Jazz Pharmaceuticals; and received patents and royalties from Athersys, Inc. He is employed at Oregon Health & Science University (OHSU). With regard to the consultant services and payment from Novartis, this potential conflict of interest has been reviewed and managed by OHSU. E.K.W. has provided consultancy to, held membership on the board of directors or advisory committees for, and received research funding from Novartis; received travel funding for the European Hematology Association and research funding from Pharmacyclics; received research funding from Celldex; provided consultancy to Kalytera; and provided consultancy to and has equity ownership in Cambium Medical Technologies. U.J. has provided consultancy to, received honoraria and researching funding from, and held membership on the board of directors or advisory committees for Novartis, Roche, and Gilead; provided consultancy to, received honoraria from, and held membership on the board of directors or advisory committees at Janssen and Celgene; provided consultancy to and received honoraria from AbbVie; held membership on the board of directors or advisory committees at Mundipharma, Takeda-Millennium, Amgen, AOP Orphan, GSK, Infinity, and Bioverativ; and received research funding from MSD. I.F. has provided consultancy to AbbVie, AstraZeneca, Novartis, Merck, Janssen, Seattle Genetics, Gilead, Lundbeck, F. Hoffmann-La Roche Ltd, and Celgene. J.M. has received honoraria and other expenses, including travel accommodations and speaker fees, from Kite Pharma; received honoraria, speaker fees, and research funding from Novartis; and received research funding from Fresenius Biotech, Astellas Pharma, Bellicum Pharmaceuticals, Gamida Cell, and Pluristem Ltd. H.H. has held membership on the board of directors or advisory committees at Novartis, Takeda, Gilead, and Celgene, and received research funding from Roche. S.J. has provided consultancy to and received research funding from Novartis and Kite Pharma, and provided consultancy to Juno. S.J.S. has provided consultancy to, received honoraria and research funding from, and held membership on the board of directors or advisory committees for Celgene; provided consultancy to and received honoraria from Dava Oncology; received honoraria and research funding from Genentech; held membership on the board of directors or advisory committees at Gilead; provided consultancy to and received honoraria and research funding from Merck; received honoraria and research funding from and held membership on the board of directors or advisory committees for Novartis; provided consultancy to, received honoraria from, and held membership on the board of directors or advisory committees for Nordic Nanovector. M.R.B. is employed at United Healthcare and has provided consultancy to and held membership on the board of directors or advisory committees for Seattle Genetics; received honoraria from and participated in the speakers bureau at Celgene; and participated in the speakers bureaus at Juneau Therapeutics and Novartis. J.R.W. has held membership on the board of directors or advisory committees for Novartis, Apotex, Kite Pharma, and Celgene. S.M. has provided consultancy to and received honoraria (personal) from Novartis; received honoraria (via institution) from and participated in the speakers bureau at Celgene; held membership on and is head of the data safety monitoring board at, participated in the speakers bureau at, and received honoraria (via institution) from Miltenyi; participated in the speakers bureau at and received honoraria (via institution) from Kiadis; is part of an expert panel at and received honorarium (via institution) from Bellicum; and received honoraria (via institution) from and participated in the speakers bureau at Gilead. T.T. has provided consultancy to, received honoraria from, and held membership on the board of directors or advisory committees for Novartis; provided consultancy to, held membership on the board of directors or advisory committees for, and received research funding from Takeda and Kyowa-Hakko Kirin; provided consultancy to and received honoraria from MSD; received honoraria and research funding from Bristol-Myers Squibb and Chugai; and received honoraria from Pfizer and Celgene. V.B. has held membership on the board of directors or advisory committees for Kite Pharma, and received research funding from GT Biopharma and Gamida Cell. S.R.F. has provided consultancy to and received honoraria and travel expenses from Novartis; received honoraria from and participated in the speakers bureau at Celgene; received honoraria from Amgen; participated in the speakers bureau at Janssen; and received travel expenses from Jazz Pharma. P.B. has provided consultancy to and received honoraria from Novartis. G.A.S. has provided consultancy to and received honoraria from Novartis; received honoraria from, held membership on an advisory board for, and received research funding from Celgene; received honoraria from AbbVie, Acerta, Amgen, Epizyme, Merck, Morphosys, Pfizer, Takeda, and Servier; and received honoraria from and help membership on advisory boards for Gilead, Janssen, and Servier. J.Z., R.T., L.D.P., and Q.M. are employed at Novartis. C.S.T. has received honoraria and research funding from AbbVie, Janssen, and Beigene.

© 2020 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Mean change from baseline in FACT-G domains in patients with a CR or PR. Improved scores were observed across all categories of FACT-G assessment, which includes emotional, function, physical, and social/family categories. FACT-G, functional assessment of cancer therapy-general. Error bars represent standard error of the mean. Reproduced with permission from Tam et al.

Figure 2.

Mean changes from baseline in SF-36 in patients with a CR or PR. Scores above the MCID were observed in 5 of 8 subscales, which included general health, vitality, physical function, role-emotional, role-physical, and social-functioning. The total scores of physical health and mental health improved and physical health total score surpassed the MCID at month 3, 6, and 18 time points. Error bars represent standard error of the mean. Reproduced with permission from Tam et al.