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Efficacy of CD19 directed therapies in patients with relapsed or refractory large b-cell lymphoma relapsing after CD19 directed chimeric antigen receptor T-cell therapy

Bone Marrow Transplantation volume 59, pages 211–216 (2024)Cite this article

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Abstract

Outcomes are poor for patients with relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL) post chimeric antigen receptor T-cell (CAR-T) therapy. Two CD19-directed therapies, tafasitamab- cxix plus lenalidomide (tafa-len) and loncastuximab tesirine (loncaT) are approved in R/R LBCL. The efficacy of these CD19 directed therapies in patients who relapse after CD19 directed CAR-T (CD19-CART) therapy is not well understood. We conducted a multi-center study of patients with R/R LBCL that received either tafa-len or loncaT at any timepoint for R/R disease after CD19-CART therapy. Fifty-three patients were included in this study with the median follow up of 56 (9.1–199) weeks from CAR-T infusion. Median number of systemic therapies pre–CAR-T therapy was 3 (range: 1–6); axicabtagene ciloleucel was the most utilized CAR-T product (n = 32,60%). Median time from CAR-T therapy to tafa-len or loncaT was 7.3 (1.2–38.2) months with median number of lines of therapy between CAR-T therapy and these regimens of 1 (0–5). Combined overall response rate and complete response rates were 27% and 10%, respectively. Median duration of response was 13.3 (2.1–56.7) weeks. In this real-world study, the use of currently approved CD19-directed therapies to treat R/R LBCL after CD19-CAR-T therapy showed limited clinical activity and duration of responses.

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The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, USA

    Madiha Iqbal & Mohamed A. Kharfan-Dabaja

  2. Cleveland Clinic, Cleveland, OH, USA

    Deepa Jagadeesh & Rahul Mishra

  3. Moffitt Cancer Center, Tampa, FL, USA

    Julio Chavez & Aditi Saha

  4. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    Arushi Khurana & Yi Lin

  5. Division of Hematology and Oncology, Mayo Clinic, Phoenix, AZ, USA

    Allison Rosenthal

  6. Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL, USA

    Emily Craver & Zhuo Li

  7. Arthur G. James Cancer Hospital & Richard J. Solove Research Institute, The Ohio State University, Columbus, OH, USA

    Narendranath Epperla & Kaitlin Annunzio

  8. Yale School of Medicine and Yale Cancer Center, New Haven, CT, USA

    Iris Isufi

  9. Harold C. Simmons Comprehensive Cancer Center and University of Texas Southwestern Medical Center, Dallas, TX, USA

    Farrukh T. Awan

  10. Vanderbilt- Ingram Cancer Center and Vanderbilt University Medical center, Nashville, TN, USA

    Bhagirathbhai R. Dholaria & Shakthi T. Bhaskar

  11. Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA

    Joseph E. Maakaron & Nuttavut Sumransub

  12. Moffitt Cancer Center at Memorial Healthcare System, Pembroke Pines, FL, USA

    Jose D. Sandoval-Sus & Stanislav A. Ivanov

  13. Department of Pharmacy—M Health Fairview University of Minnesota Medical Center, Minneapolis, MN, USA

    Andrew Fijalka

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  1. Madiha Iqbal
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Contributions

MI conceived the study, collected the data, wrote, and finalized the manuscript; DJ, JC, AK, AR, NE, II, FTA; BRD; JEM; JDS-S; RM; AS; KA; SRB; NS; AF; SAI; YL contributed data, reviewed, and provided feedback on the manuscript. EC; ZL provided statistical support. MA-KD conceived the study, reviewed, and finalized the manuscript.

Corresponding author

Correspondence to Madiha Iqbal.

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Competing interests

AR: educational session honoraria for Curio Science and MJH Life Sciences; NE: Research funding: Beigene, Speakers Bureau for Incyte and Beigene, Honoraria/consulting/ad boards for Merck, ADC Therapeutics, Lilly, Novartis; FTA: consultancy to Genentech, Astrazeneca, Abbvie, Janssen, Pharmacyclics, Gilead sciences, Kite pharma, Celgene, Karyopharm, MEI Pharma, Verastem, Incyte, Beigene, Johnson and Johnson, Dava Oncology, BMS, Merck, Cardinal Health, ADCT therapeutics, Epizyme, Caribou Biosciences, Cellecter Bisosciences, Loxo Oncology, and received research funding from Pharmacyclics; BD: Institutional research funding: Janssen, Angiocrine, Pfizer, Poseida, MEI, Orcabio, Wugen, Allovir; Consultancy/Advisor: Jazz, Gamida Cell, MJH BioScience, Arivan Research, BEAM therapeutics, Janssen, Atheneum; JEM: My institution receives research funding on my behalf from Gilead, Atara, CRISPR, Precision Biosciences, Scripps, FATE Therapeutics; JDSS: Speaker’s bureau: Seagen; Consultant: Abbvie, BeiGene, Genmab, Janssen, Genentech, ADC therapeutics, MassiveBio; educational programs: Curio; MAK-D: research/clinical trial with Novartis and Bristol Myers Squibb. The remaining authors have no relevant conflicts of interest to disclose.

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Iqbal, M., Jagadeesh, D., Chavez, J. et al. Efficacy of CD19 directed therapies in patients with relapsed or refractory large b-cell lymphoma relapsing after CD19 directed chimeric antigen receptor T-cell therapy. Bone Marrow Transplant 59, 211–216 (2024). https://doi.org/10.1038/s41409-023-02148-4

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