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. 2024 Jun 26;8(7):e86.
doi: 10.1002/hem3.86. eCollection 2024 Jul.

Efficacy and safety of bendamustine-containing bridging therapy in R/R LBCL patients receiving CD19 CAR T-cells

Gloria Iacoboni  1   2   3 , Mario A Sánchez-Salinas  1   2   3 , Kai Rejeski  4   5   6 , Ana Á Martín-López  7   8 , Mi Kwon  9   10 , Víctor Navarro  11 , Katarzyna A Jalowiec  12   13 , Rafael Hernani  14   15 , Juan L Reguera-Ortega  16 , Laura Gallur  1   2   3 , Viktoria Blumenberg  4   5 , María Herrero-García  17 , Claire Roddie  12 , Ana Benzaquén  14   15 , Javier Delgado-Serrano  16 , Rebeca Bailén  9   10 , Cecilia Carpio  1   2   3 , Paula Amat  14   15 , Lucia López-Corral  7   8 , Lourdes Martín-Martín  17 , Mariana Bastos  9   10 , Marion Subklewe  4   5 , Maeve O'Reilly  12 , Pere Barba  1   2   3
Affiliations

Efficacy and safety of bendamustine-containing bridging therapy in R/R LBCL patients receiving CD19 CAR T-cells

Gloria Iacoboni et al. Hemasphere. .

Abstract

Bridging therapy (BT) after leukapheresis is required in most relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients receiving chimeric antigen receptor (CAR) T cells. Bendamustine-containing regimens are a potential BT option. We aimed to assess if this agent had a negative impact on CAR-T outcomes when it was administered as BT. We included R/R LBCL patients from six centers who received systemic BT after leukapheresis from February 2019 to September 2022; patients who only received steroids or had pre-apheresis bendamustine exposure were excluded. Patients were divided into two BT groups, with and without bendamustine. Separate safety and efficacy analyses were carried out for axi-cel and tisa-cel. Of 243 patients who received BT, bendamustine (benda) was included in 62 (26%). There was a higher rate of BT progressors in the non-benda group (62% vs. 45%, p = 0.02). Concerning CAR-T efficacy, complete responses were comparable for benda versus non-benda BT cohorts with axi-cel (70% vs. 53%, p = 0.12) and tisa-cel (44% vs. 36%, p = 0.70). Also, 12-month progression-free and overall survival were not significantly different between BT groups with axi-cel (56% vs. 43% and 71% vs. 63%) and tisa-cel (25% vs. 26% and 52% vs. 48%); there were no differences when BT response was considered. CAR T-cell expansion for each construct was similar between BT groups. Regarding safety, CRS G ≥3 (6% vs. 6%, p = 0.79), ICANS G ≥3 (15% vs. 17%, p = 0.68), severe infections, and neutropenia post-infusion were comparable among BT regimens. BT with bendamustine-containing regimens is safe for patients requiring disease control during CAR T-cell manufacturing.

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Conflict of interest statement

Gloria Iacoboni: Consultancy and Honoraria: Novartis, Roche, Kite/Gilead, Bristol‐Myers Squibb, Abbvie, Janssen, Sandoz, Miltenyi, AstraZeneca. Mario A. Sánchez‐Salinas Honoraria for presentations: Kite. Support for attending meetings: Takeda. Kai Rejeski: Kite/Gilead: Research Funding, Consultancy, Honoraria and travel support; Novartis: Honoraria; BMS/Celgene: Consultancy, Honoraria; Pierre‐Fabre: travel support. Mi Kwon Consulting and lectures: Gilead, Jazz, Pfizer. Katarzyna A. Jalowiec Honoraria: Kite/Gilead. Rafael Hernani: Research: Gilead. Travel support: Gilead. Honoraria: Gilead, Janssen, MSD, Celgene, Novartis. Viktoria Blumenberg: BMS/Celgene: Research Funding; Kite/Gilead: Consultancy, Honoraria, Research Funding; Janssen: Research Funding, Honoraria; Novartis: Research Funding, Honoraria; Roche: Consultancy, Research Funding; Takeda: Research Funding. Claire Roddie: Honoraria from Kite/Gilead, Novartis, BMS, Amgen. Javier Delgado‐Serrano: Honoraria from Kite‐Gilead, Novartis, Bristol Myers Squibb, Janssen. Rebeca Bailén: Speaker and travel: Kite. Cecilia Carpio: Regeneron: Consultancy/Advisory, BMS: Consultancy/Advisory, Takeda: Consultancy/Advisory/Honoraria, Novartis: Honoraria. Marion Subklewe: receives industry research support from Amgen, Bristol‐Myers Squibb/Celgene, Gilead, Janssen, Miltenyi Biotec, Morphosys, Novartis, Roche, Seattle Genetics, and Takeda, and serves as a consultant/advisor to AvenCell, CDR‐Life, Ichnos Sciences, Incyte Biosciences, Janssen, Molecular Partners, and Takeda. She serves on the speakers' bureau at Amgen, AstraZeneca, BMS/Celgene, Gilead, GSK, Janssen, Novartis, Pfizer, Roche, and Takeda. Maeve O'Reilly: Honoraria from Kite, Novartis, Janssen. Advisory boards Kite and Autolus. Travel grant Kite and Novartis. Pere Barba: Allogene: Honoraria; Amgen: Honoraria; BMS: Honoraria; Kite/Gilead: Honoraria; Janssen: Honoraria; Jazz Pharmaceuticals: Honoraria; Miltenyi: Honoraria; Novartis: Honoraria; Nektar: Honoraria.

Figures

Figure 1
Figure 1
Response rates to axi‐cel and tisa‐cel according to the bridging treatment (including bendamustine and non‐bendamustine regimens).
Figure 2
Figure 2
Survival outcomes according to the type of bridging (bendamustine vs. non‐bendamustine) and the response to bridging (nonprogressors [CR/PR/SD] vs. progressors [PD]). (A) Progression‐free survival for axi‐cel patients. (B) Progression‐free survival for tisa‐cel patients. (C) Overall survival for axi‐cel patients. (D) Overall survival for tisa‐cel patients.
Figure 3
Figure 3
CAR T‐cell expansion analysis according to the type of bridging. (A) Peak CAR T‐cell expansion and area under the curve during the first 28 days after infusion (AUC0–28) in axi‐cel (A) and tisa‐cel (B) patients receiving bendamustine or non‐bendamustine bridging regimens. Values stand for median peak (interquartile range, IQR).
Figure 4
Figure 4
Comparison of the severity of infectious events after CAR T‐cell infusion in patients receiving bendamustine and non‐bendamustine bridging regimens. This analysis only included patients who experienced at least one infectious event.
See this image and copyright information in PMC

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