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Clinical Trial
. 2025 Dec 23;9(24):6292-6304.
doi: 10.1182/bloodadvances.2024015787.

Brentuximab vedotin addition to gemcitabine in relapsed or refractory peripheral T-cell lymphoma: a LYSA phase 2 study

Olivier Tournilhac  1 , Kamal Bouabdallah  2 , Solène Lecolant  3 , Maya Hacini  4 , Kamel Laribi  5 , Sébastien Bailly  1 , Thibaut Belmondo  3   6 , Marie Maerevoet  7 , Loic Ysebaert  8 , Stéphanie Guidez  9 , Steven Le Gouill  10 , Christophe Bonnet  11 , Marc André  12 , Jehan Dupuis  13 , Catherine Thieblemont  14 , Emmanuel Bachy  15 , Nicolas Daguindau  16 , Franck Morschhauser  17 , Sabine Tricot  18 , Charline Moulin  19 , Anne Banos  20 , Roch Houot  21 , Adrien Chauchet  22 , Emmanuel Gyan  23 , Guillaume Cartron  24 , Hassan Farhat  25 , Vincent Camus  26 , Bernard Drenou  27 , Hacene Zerazhi  28 , David Sibon  13   29 , Emmanuelle Nicolas-Virelizier  30 , Caroline Delette  31 , Sylvia Snauwaert  32 , Sarah Bailly  33 , Richard Delarue  29 , Sylvain Carras  34 , Albane Ledoux-Pilon  1 , Marie-Cécile Parrens  2 , Samuel Griolet  35 , Philippe Gaulard  36 , Marie-Hélène Delfau-Larue  3 , Laurence de Leval  37 , Gandhi Laurent Damaj  38
Affiliations
Clinical Trial

Brentuximab vedotin addition to gemcitabine in relapsed or refractory peripheral T-cell lymphoma: a LYSA phase 2 study

Olivier Tournilhac et al. Blood Adv. .

Abstract

We aim to evaluate the efficacy of brentuximab vedotin (BV) combined with gemcitabine (GBV) followed by BV maintenance in relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL). Patients with at least 5% CD30+ cells by immunohistochemistry received 4 GBV induction (28 days) cycles of gemcitabine 1000 mg/m2 (day 1, day 15) plus BV 1.8 mg/kg (day 8) followed, in responding patients, by up to 12 BV maintenance (21 day) cycles. Primary end point was overall response rate (ORR) after 4 induction cycles by computed tomography scan-based Lugano criteria. Of 71 enrolled patients (median age of 66 years), 80.3% had received 1 previous line and 60.6% were refractory. The diagnoses per pathology central review were follicular helper T-cell lymphomas (TFHL; 47.9%), anaplastic large-cell lymphomas (ALCL; anaplastic lymphoma kinase [ALK] negative [19.7%] and ALK+ [7%]), peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS; 12.7%), and other entities (12.7%). In the intention-to-treat analysis, ORR was 46.5%, with 19.7% complete response. Twenty-eight patients received maintenance. Grade 3 to 4 adverse events reported in ≥10% of patients during induction comprised neutropenia (55%), thrombocytopenia (14%), anemia (21%), and infection (14%); during maintenance comprised neutropenia (39%), thrombocytopenia (21%), and peripheral neuropathy (14%). With a median follow-up of 32.6 months, the median duration of response, progression-free, and overall survival were 15.8, 4.5, and 12.9 months, respectively. Efficacy, higher in ALCL, was present in the TFHL and PTCL-NOS group. A negative association of high baseline soluble CD30 on both response and survival was found, which, in ad hoc analysis, appeared highly relevant in patients with TFHL and PTCL-NOS. This trial was registered at the European Union Drug Regulating Authorities Clinical Trials database as #2017-000409-1, and at www.clinicaltrials.gov as #NCT03496779.

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Conflict of interest statement

Conflict-of-interest disclosure: O.T. received travel grants and honoraria from Takeda, AbbVie, BeiGene/BeOne, and AstraZeneca; research support from Takeda; and honoraria from Ideogen. M.A. served on advisory boards for Takeda, Bristol Myers Squibb, Gilead, Incyte, Sobi, and BeiGene; received institutional research grants from Roche, Johnson & Johnson, and Takeda; and travel grants from Roche, Bristol Myers Squibb, Celgene, Gilead, AbbVie, AstraZeneca, and Takeda. J.D. received travel grants from Janssen and BeiGene/BeOne; and honoraria from BeiGene/BeOne and AstraZeneca. S.T. received travel grants from Takeda and BeiGene/BeOne. G.C. served as a consultant for Takeda, Novartis, Bristol Myers Squibb, Roche, Ownards Therapeutics, MAbQI, and AbbVie; received honoraria from Takeda, AstraZeneca, Bristol Myers Squibb, Gilead, Roche, Janssen, and AbbVie; and travel grants from Novartis, Gilead, Roche, and Janssen. V.C. received honoraria from Incyte, AbbVie, AstraZeneca, Bristol Myers Squibb, Ideogen, Janssen, Kiowa Kirin, Kite/Gilead, Lilly, Novartis, Octapharma, Secura Bio, Pfizer, Sanofi, and Takeda. D.S. received travel grants and honoraria from Takeda. R.D. is an employee and stock owner of BeiGene/BeOne. P.G. received travel grants, honoraria, and research support from Takeda. L.d.L. served as a consultant for Roche; on advisory boards for AbbVie and Novartis; as a speaker for Takeda, all institutional; and received travel support from Roche. G.D. received travel support from Takeda and Amgen; and research support from Takeda and Ideogen. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
CONSORT diagram. Protocol deviations were: in 1 patient, the administration of a fifth BV induction cycle before a consolidation with auto-HCT; and 1 patient, the absence of a 12th cycle of maintenance. “Other reason” means patients withdrawn for transplantation program as permitted by protocol after initial evaluation, either before (n = 4) or during maintenance (n = 5).
Figure 2.
Figure 2.
Outcome. (A) Kaplan-Meier estimates of duration of response of patients achieving either CR or PR after 4 cycles of GBV induction. (B-D) Kaplan-Meier estimates of (B) time to treatment failure, (C) PFS, and (D) OS for the entire cohort. (E) Course of patients with confirmed PTCL and at least 12 months without progression from inclusion. CL, confidence limit; CMR, complete metabolic response; DEV, study deviation; Histo, histology; uncl., unclassified; NA, not applicable; NE, nonevaluable; PMR, partial metabolic response; PTD, primary treatment discontinuation, not related to disease progression. ∗Previous autologous transplantation.
Figure 2.
Figure 2.
Outcome. (A) Kaplan-Meier estimates of duration of response of patients achieving either CR or PR after 4 cycles of GBV induction. (B-D) Kaplan-Meier estimates of (B) time to treatment failure, (C) PFS, and (D) OS for the entire cohort. (E) Course of patients with confirmed PTCL and at least 12 months without progression from inclusion. CL, confidence limit; CMR, complete metabolic response; DEV, study deviation; Histo, histology; uncl., unclassified; NA, not applicable; NE, nonevaluable; PMR, partial metabolic response; PTD, primary treatment discontinuation, not related to disease progression. ∗Previous autologous transplantation.
Figure 3.
Figure 3.
Reponse and outcome according to CD30-associated parameters in TFHL and PTCL-NOS (exploratory analysis). ORR (A-B) and Kaplan-Meier estimate, with number of patients at risk and 95% CL of DOR (C-D), PFS (E-F), and OS (G-H) with relative impact of IHC CD30 expression on neoplastic cells (<10% vs ≥10%; left panels) and of enzyme-linked immunosorbent assay baseline sCD30 level (≤120 ng/mL vs >120 ng/mL; right panels). NA, not applicable; Pcorr, corrected P-value.
See this image and copyright information in PMC

References

    1. Laurent C, Baron M, Amara N, et al. Impact of expert pathologic review of lymphoma diagnosis: study of patients from the French Lymphopath Network. JCO. 2017;35(18):2008–2017. - PubMed
    1. Mak V, Hamm J, Chhanabhai M, et al. Survival of patients with peripheral T-cell lymphoma after first relapse or progression: spectrum of disease and rare long-term survivors. JCO. 2013;31(16):1970–1976. - PubMed
    1. Chihara D, Fanale MA, Miranda RN, et al. The survival outcome of patients with relapsed/refractory peripheral T-cell lymphoma-not otherwise specified and angioimmunoblastic T-cell lymphoma. Br J Haematol. 2017;176(5):750–758. - PMC - PubMed
    1. Bellei M, Foss FM, Shustov AR, et al. The outcome of peripheral T-cell lymphoma patients failing first-line therapy: a report from the prospective, International T-Cell Project. Haematologica. 2018;103(7):1191–1197. - PMC - PubMed
    1. Maurer MJ, Ellin F, Srour L, et al. International assessment of event-free survival at 24 months and subsequent survival in peripheral T-cell lymphoma. JCO. 2017;35(36):4019–4026. - PMC - PubMed

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