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. 2020 Nov 24;4(22):5607-5615.
doi: 10.1182/bloodadvances.2020003001.

Predictive factors of early progression after CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma

Laetitia Vercellino  1 , Roberta Di Blasi  2 , Salim Kanoun  3 , Benoit Tessoulin  4   5   6 , Cedric Rossi  7 , Maud D'Aveni-Piney  8   9 , Lucie Obéric  10 , Caroline Bodet-Milin  11 , Pierre Bories  10 , Pierre Olivier  12 , Ingrid Lafon  7 , Alina Berriolo-Riedinger  13 , Eugenio Galli  2 , Sophie Bernard  2 , Marie-Thérèse Rubio  8   9 , Celine Bossard  14 , Veronique Meignin  15 , Pascal Merlet  1 , Pierre Feugier  8   16 , Steven Le Gouill  4 , Loic Ysebaert  3 , Olivier Casasnovas  7 , Michel Meignan  17 , Sylvie Chevret  18 , Catherine Thieblemont  2   19
Affiliations

Predictive factors of early progression after CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma

Laetitia Vercellino et al. Blood Adv. .

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has emerged as an option for relapsed/refractory aggressive B-cell lymphomas that have failed 2 lines of therapy. Failures usually occur early after infusion. The purpose of our study was to identify factors that may predict failure, particularly early progression (EP), within the first month after infusion. Characteristics of 116 patients were analyzed at the time of decision (TD) to use commercial CAR (axicabtagene ciloleucel, n = 49; tisagenlecleucel n = 67) and at the time of treatment (TT), together with total metabolic tumor volume (TMTV) at TT. With a median follow-up of 8.2 months, 55 patients failed treatment; 27 (49%) were early progressors. The estimated 12-month progression-free survival (PFS) and overall survival (OS) were 47.2% (95% confidence interval [CI], 38.0-58.6) and 67.0% (95% CI, 57-79), respectively. Univariate analyses for PFS and OS identified Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2, stage III/IV disease, extranodal (EN) sites ≥2, elevated lactate dehydrogenase (LDH), increased C-reactive protein (CRP), high International Prognostic Index at TD and at TT, as well as increased CRP, bulky mass, and high TMTV at TT, as risk factors. Multivariate analyses for PFS, EP, and OS identified elevated LDH and EN sites ≥2 at TD and the same predictors at TT (ie, increased CRP, EN sites ≥2, and TMTV >80 mL). In summary, risk factors identified for early progression at TD and at TT were EN involvement (≥2 sites) and lymphoma burden (LDH, TMTV).

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Conflict of interest statement

Conflict-of-interest disclosure: R.D.B. has served on advisory boards for and received honoraria from Gilead Sciences and Novartis. L.O. has served on an advisory board for and received honoraria from Janssen Pharmaceuticals outside of the submitted work. P.F. has received honoraria from, had travel accommodations paid by, and has acted in a consulting/advisory role for Roche/Genentech, Janssen Pharmaceuticals, Gilead Sciences, and AbbVie. S.L.G. has acted in an advisory role for and received honoraria from Celgene, Roche, Gilead Sciences, Epizyme, Bristol Myers Squibb, Bayer, and Novartis and has received honoraria from Janssen Pharmaceuticals. L.Y. has received honoraria from, had travel accommodations paid by, and has acted in a consulting/advisory role for Roche/Genentech, Janssen Pharmaceuticals, Gilead Sciences, and AbbVie. O.C. has received research funding from Roche, Takeda, and Gilead Sciences and has served on advisory boards for and received honoraria from Celgene, Roche, Takeda, Gilead Sciences, Bristol Myers Squibb, Merck, AbbVie, and Janssen Pharmaceuticals outside of the submitted work. C.T. has received honoraria from Roche, Amgen, Janssen Pharmaceuticals, Celgene, and Gilead Sciences/Kyte; has acted in a consulting/advisory role from Roche, Gilead Sciences, Janssen Pharmaceuticals, Celgene, and Novartis; and has received research funding from and had travel, accommodation, and expenses paid by Roche and Novartis. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
OS and PFS of the 116 patients treated with commercialized CAR T cells (tisa-cel, n = 49; axi-cel, n = 67). (A) OS probability. (B) PFS probability.
Figure 2.
Figure 2.
PFS and OS considering 3 groups of patients (ie, patients with EN sites ≥2 and TMTV >80 mL, those presenting neither of these parameters, or those presenting only 1 parameter compared with discrimination by the R-IPI. Our model is able to differentiate 3 well-balanced groups with equivalent performance. (A) PFS. (B) OS.
See this image and copyright information in PMC

Comment in

References

    1. Crump M, Neelapu SS, Farooq U, et al. . Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2018;131(5):587-588. - PMC - PubMed
    1. Van Den Neste E, Schmitz N, Mounier N, et al. . Outcomes of diffuse large B-cell lymphoma patients relapsing after autologous stem cell transplantation: an analysis of patients included in the CORAL study. Bone Marrow Transplant. 2017;52(2):216-221. - PubMed
    1. Gisselbrecht C, Glass B, Mounier N, et al. . Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(27):4184-4190. - PMC - PubMed
    1. Neelapu SS, Locke FL, Bartlett NL, et al. . Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531-2544. - PMC - PubMed
    1. Schuster SJ, Bishop MR, Tam CS, et al. . Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380(1):45-56. - PubMed