Recent Bendamustine Treatment Before Apheresis Has a Negative Impact on Outcomes in Patients With Large B-Cell Lymphoma Receiving Chimeric Antigen Receptor T-Cell Therapy

Author(s): Gloria Iacoboni, MD, PhD^1,2,3; Víctor Navarro, BSc⁴; Ana África Martín-López, MD^5,6; Kai Rejeski, MD^7,8,9; Mi Kwon, MD, PhD^10,11; Katarzyna Aleksandra Jalowiec, MD^12,13; Paula Amat, MD^14,15; Juan Luis Reguera-Ortega, MD¹⁶; Laura Gallur, MD^1,2,3; Viktoria Blumenberg, MD^7,8,9; Sara Gutiérrez-Herrero, PhD¹⁷; Claire Roddie, MD, PhD¹²; Ana Benzaquén, MD^14,15; Javier Delgado-Serrano, MD¹⁶; Mario Andrés Sánchez-Salinas, MD^1,2,3; Rebeca Bailén, MD, PhD^10,11; Cecilia Carpio, MD^1,2,3; Lucia López-Corral, MD^5,6; Rafael Hernani, MD^14,15; Mariana Bastos, MD, PhD^10,11; Maeve O’Reilly, MD¹⁷; Lourdes Martín-Martín, PhD¹⁷; Marion Subklewe, MD, PhD^7,8,9; Pere Barba, MD, PhD^1,2,3

Source: https://doi.org/10.1200/JCO.23.01097

Dr. Anjan Patel's Thoughts

This gives more credence to the idea of avoiding bendamustine before CAR T therapy. Patients exposed to bendamustine had about a 20% lower overall response rate (ORR), 50% shorter progression-free survival (PFS) and >50% shorter overall survival (OS) compared to those who were bendamustine naive. Although other factors may also play a role here, these seem to be significant differences and should make it clear that one should not use this drug before pursuing CAR T therapy.

PURPOSE

Approximately 30%-40% of patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) infused with CD19-targeted chimeric antigen receptor (CAR) T cells achieve durable responses. Consensus guidelines suggest avoiding bendamustine before apheresis, but specific data in this setting are lacking. We report distinct outcomes after CAR T-cell therapy according to previous bendamustine exposure.

METHODS

The study included CAR T-cell recipients from seven European sites. Safety, efficacy, and CAR T-cell expansion kinetics were analyzed according to preapheresis bendamustine exposure. Additional studies on the impact of the washout period and bendamustine dose were performed. Inverse probability treatment weighting (IPTW) and propensity score matching (PSM) analyses were carried out for all efficacy comparisons between bendamustine-exposed and bendamustine-naïve patients.

RESULTS

The study included 439 patients with R/R LBCL infused with CD19-targeted commercial CAR T cells, of whom 80 had received bendamustine before apheresis. Exposed patients had significantly lower CD3+ cells and platelets at apheresis. These patients had a lower overall response rate (ORR, 53% v 72%; P < .01), a shorter progression-free survival (PFS, 3.1 v 6.2 months; P = .04), and overall survival (OS, 10.3 v 23.5 months; P = .01) in comparison with the bendamustine-naïve group. Following adjustment methods for baseline variables, these differences were mitigated. Focusing on the impact of bendamustine washout before apheresis, those with recent (<9 months) exposure (N = 42) displayed a lower ORR (40% v 72%; P < .01), shorter PFS (1.3 v 6.2 months; P < .01), and OS (4.6 v 23.5 months; P < .01) in comparison with bendamustine-naïve patients. These differences remained significant after IPTW and PSM analysis. Conversely, the cumulative dose of bendamustine before apheresis did not affect CAR-T efficacy outcomes.

CONCLUSION

Recent bendamustine exposure before apheresis was associated with negative treatment outcomes after CD19-targeted CAR T-cell therapy and should be therefore avoided in CAR T-cell candidates.

Author Affiliations

¹Department of Hematology, University Hospital Vall d’Hebron, Barcelona, Spain; ²Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; ³Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain; ⁴Oncology Data Science (ODySey) Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; ⁵Hematology Department, Hospital Clínico Universitario de Salamanca, IBSAL, CIBERONC, Salamanca, Spain; ⁶Centro de Investigación del Cáncer-IBMCC, Salamanca, Spain; ⁷Department of Medicine III, University Hospital, LMU Munich, Munich, Germany; ⁸Laboratory for Translational Cancer Immunology, Gene Center of the LMU Munich, Munich, Germany; ⁹German Cancer Consortium (DKTK) and Bavarian Center for Cancer Research (BZKF), partner site Munich, Munich, Germany; ¹⁰Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; ¹¹Gregorio Marañón Health Research Institute (IiSGM), Madrid, Spain; ¹²Hematology Department, University College London Cancer Institute, London, United Kingdom; ¹³Department of Hematology and Central Hematology Laboratory, University Hospital of Bern, Bern, Switzerland; ¹⁴Haematology Department, Hospital Clínico Universitario, Valencia, Spain; ¹⁵INCLIVA Research Institute, Valencia, Spain; ¹⁶Hematology Department, Hospital Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS)/CSIC, Universidad de Sevilla, Sevilla, Spain; ¹⁷Cancer Research Centre (IBMCC, USAL-CSIC), Institute for Biomedical Research of Salamanca (IBSAL) and Department of Medicine and Cytometry Service (NUCLEUS Research Support Platform), University of Salamanca (USAL), Salamanca, Spain

High-Dose Methotrexate as CNS Prophylaxis in High-Risk Aggressive B-Cell Lymphoma

Good review of high-risk patients, showing that prophylactic high dose MTX did not have lower risk of CNS disease.

Lenalidomide plus rituximab for the initial treatment of frail older patients with DLBCL: the FIL_ReRi phase 2 study

There are too many options for DLBCL now with monoclonal antibodies, bispecific and CAR-T therapy, but in frail patients, this might be an option. Tafatistamab with lenalidomide had higher ORR (55vs 50) and CR( 37 vs 27%) but this is comparing different trials, and this trial had mostly elderly pts, I do feel tafatistamab is fairly well tolerated though. But when in doubt this seems to be a fair option.

Safety and efficacy of tafasitamab with or without lenalidomide added to first-line R-CHOP for DLBCL: the phase 1b First-MIND study

Speaking of tafatistamab, it seems it is fairly tolerable in first line with almost 75% CR added to RCHOP, adding lenolidomie 86% CR, but this is a phase 1b. Awaiting phase 3 data, we may have another first line option or may the first line option.

Survival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma

CAR-T for second line is better than standard of care, the question is: how about compared to BITE therapy? Future is exciting for those patients.

Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma: final analysis of KEYNOTE-170

Pembrolizumab in lymphoma, this is not a common one, usually in young females, could be hard to treat.