-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

3504 Bendamustine Versus Fludarabine and Cyclophosphamide for Lymphodepletion Prior to CAR-T Therapy

Program: Oral and Poster Abstracts
Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster II
Hematology Disease Topics & Pathways:
Biological therapies, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Therapies
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Uttam K Rao, MD, MBA1, Betsy Blunk2*, Carlos Bachier, MD3, Vikas Bhushan, MD4*, Jose Carlos Cruz, MD3*, Mohammed Elayan, PharmD2*, Ian W. Flinn, MD, PhD5, Tara Gregory, MD6, Charles F. LeMaistre, MD2, Navneet Majhail, MD, MS, FASTCT2, Shahbaz A. Malik, MD1, Casey Martin7*, Michael B. Maris, MD6, John Mathews, MD4*, Luke Mountjoy, DO6, Jeremy M. Pantin, MD5*, Aravind Ramakrishnan, M.D.1, Paul Shaughnessy, MD3, Michael T. Tees, MD6, Estil A. Vance, MD4*, Behyar Zoghi, MD, PhD, FACP3* and Minoo Battiwalla, MD5

1Sarah Cannon Transplant and Cellular Therapy Program at St. David's South Austin Medical Center, Austin, TX
2Sarah Cannon Transplant and Cellular Therapy Network, Nashville, TN
3Sarah Cannon Transplant and Cellular Therapy Program at Methodist Hospital, San Antonio, TX
4Sarah Cannon and Texas Oncology Transplant and Cellular Therapy Program at Medical City Dallas, Dallas, TX
5Sarah Cannon Transplant and Cellular Therapy Program at TriStar Centennial Medical Center, Nashville, TN
6The Colorado Blood Cancer Institute a part of Sarah Cannon Cancer Institute at Presbyterian/St Luke's Medical Center, Denver, CO
7Genospace, Boston, MA


As CAR-T treatment volumes and approved indications rapidly expand, identifying optimal lymphodepleting chemotherapy (LDC) regimens is an urgent and unmet need. A combination of fludarabine and cyclophosphamide (flu/cy) is most commonly performed. However, an ongoing international fludarabine shortage1 has led to the use of bendamustine (benda), a potent lymphotoxin, as LDC, with initial reports suggesting similar efficacy with less toxicity2, 3. We performed a multi-center retrospective analysis of patients with non-Hodgkin lymphoma (NHL) who have received benda or flu/Cy LDC prior to infusion of FDA-approved CAR-T products across the Sarah Cannon Transplant and Cellular Therapy Network (SCTCTN). We hypothesized that, compared with flu/cy, benda is noninferior in terms of lymphodepletion, hematologic recovery, CAR-T response and toxicities, as well as resource utilization.


We retrospectively analyzed 215 NHL patients receiving benda (46) or flu/cy (169) LDC prior to commercial CAR-T from 2018-2023 in the SCTCTN CAR-T registry. Patients on clinical trials, who received CAR-T for other malignancies than NHL, or were within 30 days of CAR-T infusion were excluded. Absolute lymphocyte count (ALC), neutrophil, and platelet kinetics were measured. Cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) were graded according to consensus criteria of the American Society of Transplant and Cellular Therapy (ASTCT), and the occurrence, maximum grade, days to onset/resolution, and tocilizumab dosing were recorded.

Overall survival (OS), progression free survival (PFS), and resource utilization (length of stay in hospital and ICU requirement) were recorded.


Characteristics of patients receiving benda and flu/cy were matched in terms of age, gender, race, ethnicity, NHL subtype, performance status. Flu/cy and benda produced deep absolute lymphocyte count (ALC) nadirs by the date of CAR-T infusion (day 0) with subsequent partial recovery by day 30. Lymphodepletion nadir at day 0 was deeper [P<0.001] with flu/cy (ALC 0.03 K/uL, IQR range 0.01-0.05) than benda (ALC 0.21 K/uL, IQR range 0.1-0.3) but not at other time points. The kinetics of neutrophil and platelet recovery were similar between groups suggesting an equivalent extent of marrow suppression. Parameters of resource utilization such as inpatient hospitalization, length of stay, ICU utilization, and the use of tocilizumab were similar between flu/cy and benda recipients.


In a large cohort of real-world CAR-T recipients, benda produced efficient lymphodepletion and equivalent outcomes compared to traditional flu/cy. While flu/cy produces a deeper nadir than benda at day 0, this difference did not exert clinical relevance.

Disclosures: Rao: Janssen: Honoraria. Flinn: TG Therapeutics: Consultancy; Myeloid Therapeutics: Consultancy; Vincerx Pharma: Consultancy; Innocare Pharma: Consultancy; Kite: Consultancy; Novartis: Consultancy; Secura Bio: Consultancy; Servier Pharma: Consultancy; Hutchinson MediPharma: Consultancy; Genmab: Consultancy; Genentech: Consultancy; Century Therapeutics: Consultancy; BeiGene: Consultancy; AbbVie: Consultancy. Majhail: Anthem Inc: Membership on an entity's Board of Directors or advisory committees. Pantin: Omeros, Sanofi: Speakers Bureau; Orca Bio: Research Funding; Omeros: Honoraria. Shaughnessy: Sanofi: Speakers Bureau; BMS: Speakers Bureau. Battiwalla: Novartis: Research Funding; Fate Therapeutics: Research Funding.

*signifies non-member of ASH