Skip to main content
SpringerLink
Log in

Efficacy of programmed cell death 1 inhibitor maintenance after chimeric antigen receptor T cells in patients with relapsed/refractory B-cell non-Hodgkin-lymphoma

  • Research
  • Published:
Cellular Oncology Aims and scope Submit manuscript

Abstract

Introduction

Chimeric antigen receptor (CAR)-T cells obtained long-term durability in about 30% to 40% of relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). Maintenance therapy after CAR-T is necessary, and PD1 inhibitor is one of the important maintenance therapy options.

Methods

A total of 173 r/r B-NHL patients treated with PD1 inhibitor maintenance following CD19/22 CAR-T therapy alone or combined with autologous hematopoietic stem cell transplantation (ASCT) from March 2019 to July 2022 were assessed for eligibility for two trials. There were 81 patients on PD1 inhibitor maintenance therapy.

Results

In the CD19/22 CAR-T therapy trial, the PD1 inhibitor maintenance group indicated superior objective response rate (ORR) (82.9% vs 60%; P = 0.04) and 2-year progression-free survival (PFS) (59.8% vs 21.3%; P = 0.001) than the non-maintenance group. The estimated 2-year overall survival (OS) was comparable in the two groups (60.1% vs 45.1%; P = 0.112). No difference was observed in the peak expansion levels of CD19 CAR-T and CD22 CAR-T between the two groups. The persistence time of CD19 and CD22 CAR-T in the PD1 inhibitor maintenance group was longer than that in the non-maintenance group. In the CD19/22 CAR-T therapy combined with ASCT trial, no significant differences in ORR (81.4% vs 84.8%; P = 0.67), 2-year PFS (72.3% vs 74.9%; P = 0.73), and 2-year OS (84.1% vs 80.7%; P = 0.79) were observed between non-maintenance and PD1 inhibitor maintenance therapy groups. The peak expansion levels and duration of CD19 and CD22 CAR-T were not statistically different between the two groups. During maintenance treatment with PD1 inhibitor, all adverse events were manageable. In the multivariable analyses, type and R3m were independent predictive factors influencing the OS of r/r B-NHL with PD1 inhibitor maintenance after CAR-T therapy.

Conclusion

PD1 inhibitor maintenance following CD19/22 CAR-T therapy obtained superior response and survival in r/r B-NHL, but not in the trial of CD19/22 CAR-T cell therapy combined with ASCT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

The data supporting the current study will be made available by the authors, without reservation.

Abbreviations

CAR-T:

Chimeric antigen receptor T-cell

r/r:

Relapsed or refractory

B-NHL:

B-cell non-Hodgkin-lymphoma

PD1:

Programmed cell death protein 1

ASCT:

Autologous hematopoietic stem cell transplantation

ORR:

Objective response rate

PFS:

Progression-free survival

OS:

Overall survival

DLBCL:

Diffuse large B-cell lymphoma

PMBCL:

Primary mediastinal large B-cell lymphoma

FL:

Follicular lymphoma

PDL1:

Programmed cell death 1 ligand 1

PBMC:

Peripheral blood mononuclear cell

CT:

Computed tomography

CRS:

Cytokine release syndrome

ICANS:

Immune effector cell-associated neurotoxicity syndrome

OR:

Objective response

CR:

Complete remission

PR:

Partial remission

SD/PD:

Stable disease/progressive disease

DOR:

Duration of response

IPI:

International prognostic index

R3m:

OR at month 3

References

  1. S.S. Neelapu, F.L. Locke, N.L. Bartlett, L.J. Lekakis, D.B. Miklos, C.A. Jacobson, I. Braunschweig, O.O. Oluwole, T. Siddiqi, Y. Lin, et al., Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N. Engl. J. Med. 377(26), 2531–2544 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. S.J. Schuster, M.R. Bishop, C.S. Tam, E.K. Waller, P. Borchmann, J.P. McGuirk, U. Jager, S. Jaglowski, C. Andreadis, J.R. Westin, et al., Tisagenlecleucel in adult relapsed or refractory diffuse large B-Cell lymphoma. N. Engl. J. Med. 380(1), 45–56 (2019)

    Article  CAS  PubMed  Google Scholar 

  3. M. Wang, J. Munoz, A. Goy, F.L. Locke, C.A. Jacobson, B.T. Hill, J.M. Timmerman, H. Holmes, S. Jaglowski, I.W. Flinn, et al., KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma. N. Engl. J. Med. 382(14), 1331–1342 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. J.S. Abramson, M.L. Palomba, L.I. Gordon, M.A. Lunning, M. Wang, J. Arnason, A. Mehta, E. Purev, D.G. Maloney, C. Andreadis, et al., Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet 396(10254), 839–852 (2020)

    Article  PubMed  Google Scholar 

  5. F.L. Locke, A. Ghobadi, C.A. Jacobson, D.B. Miklos, L.J. Lekakis, O.O. Oluwole, Y. Lin, I. Braunschweig, B.T. Hill, J.M. Timmerman, et al., Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1–2 trial. Lancet Oncol. 20(1), 31–42 (2019)

    Article  CAS  PubMed  Google Scholar 

  6. S.J. Schuster, J. Svoboda, E.A. Chong, S.D. Nasta, A.R. Mato, O. Anak, J.L. Brogdon, I. Pruteanu-Malinici, V. Bhoj, D. Landsburg, et al., Chimeric antigen receptor T cells in refractory B-cell lymphomas. N. Engl. J. Med. 377(26), 2545–2554 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. J.N. Brudno, J.N. Kochenderfer, Chimeric antigen receptor T-cell therapies for lymphoma. Nat. Rev. Clin. Oncol. 15(1), 31–46 (2018)

    Article  CAS  PubMed  Google Scholar 

  8. D.H. Yoon, M.J. Osborn, J. Tolar, C.J. Kim, Incorporation of immune checkpoint blockade into chimeric antigen receptor T cells (CAR-Ts): combination or built-in CAR-T. Int. J. Mol. Sci. 19(2), 340 (2018)

    Article  PubMed  PubMed Central  Google Scholar 

  9. N.N. Shah, T.J. Fry, Mechanisms of resistance to CAR T cell therapy. Nat. Rev. Clin. Oncol. 16(6), 372–385 (2019)

    CAS  PubMed  PubMed Central  Google Scholar 

  10. L. Cherkassky, A. Morello, J. Villena-Vargas, Y. Feng, D.S. Dimitrov, D.R. Jones, M. Sadelain, P.S. Adusumilli, Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition. J. Clin. Invest. 126(8), 3130–3144 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  11. M. Ahmadzadeh, L.A. Johnson, B. Heemskerk, J.R. Wunderlich, M.E. Dudley, D.E. White, S.A. Rosenberg, Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood 114(8), 1537–1544 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. T. Shimauchi, K. Kabashima, D. Nakashima, K. Sugita, Y. Yamada, R. Hino, Y. Tokura, Augmented expression of programmed death-1 in both neoplastic and non-neoplastic CD4+ T-cells in adult T-cell leukemia/lymphoma. Int. J. Cancer 121(12), 2585–2590 (2007)

    Article  CAS  PubMed  Google Scholar 

  13. M.R. Green, S. Rodig, P. Juszczynski, J. Ouyang, P. Sinha, E. O’Donnell, D. Neuberg, M.A. Shipp, Constitutive AP-1 activity and EBV infection induce PD-L1 in Hodgkin lymphomas and posttransplant lymphoproliferative disorders: implications for targeted therapy. Clin. Cancer Res. 18(6), 1611–1618 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. J. Kiyasu, H. Miyoshi, A. Hirata, F. Arakawa, A. Ichikawa, D. Niino, Y. Sugita, Y. Yufu, I. Choi, Y. Abe, et al., Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma. Blood 126(19), 2193–2201 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. P. Armand, S. Rodig, V. Melnichenko, C. Thieblemont, K. Bouabdallah, G. Tumyan, M. Ozcan, S. Portino, L. Fogliatto, M.D. Caballero, et al., Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma. J. Clin. Oncol. 37(34), 3291–3299 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. S. Ansell, M.E. Gutierrez, M.A. Shipp, D. Gladstone, A. Moskowitz, I. Borello, M. Popa-Mckiver, B. Farsaci, L. Zhu, A.M. Lesokhin, et al., A phase 1 study of nivolumab in combination with ipilimumab for relapsed or refractory hematologic malignancies (checkmate 039). Blood 128(22), 183–183 (2016)

    Article  Google Scholar 

  17. S.M. Ansell, M.C. Minnema, P. Johnson, J.M. Timmerman, P. Armand, M.A. Shipp, S.J. Rodig, A.H. Ligon, M.G.M. Roemer, N. Reddy, et al., Nivolumab for relapsed/refractory diffuse large B-cell lymphoma in patients ineligible for or having failed autologous transplantation: a single-arm, phase II study. J. Clin. Oncol. 37(6), 481–489 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. S.L. Maude, T.W. Laetsch, J. Buechner, S. Rives, M. Boyer, H. Bittencourt, P. Bader, M.R. Verneris, H.E. Stefanski, G.D. Myers, et al., Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N. Engl. J. Med. 378(5), 439–448 (2018)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. J.A. Fraietta, S.F. Lacey, E.J. Orlando, I. Pruteanu-Malinici, M. Gohil, S. Lundh, A.C. Boesteanu, Y. Wang, R.S. O’Connor, W.T. Hwang, et al., Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. Nat. Med. 24(5), 563–571 (2018)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. F. Li, Z. Zhang, Y. Xuan, D. Zhang, J. Liu, A. Li, S. Wang, T. Li, X. Shi, Y. Zhang, PD-1 abrogates the prolonged persistence of CD8(+) CAR-T cells with 4-1BB co-stimulation. Signal Transduct. Target Ther. 5(1), 164 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. S. Rafiq, O.O. Yeku, H.J. Jackson, T.J. Purdon, D.G. van Leeuwen, D.J. Drakes, M. Song, M.M. Miele, Z. Li, P. Wang, et al., Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor efficacy in vivo. Nat. Biotechnol. 36(9), 847–856 (2018)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. S.N. Zolov, S.P. Rietberg, C.L. Bonifant, Programmed cell death protein 1 activation preferentially inhibits CD28.CAR-T cells. Cytotherapy 20(10), 1259–1266 (2018)

    Article  CAS  PubMed  Google Scholar 

  23. E. Hui, J. Cheung, J. Zhu, X. Su, M.J. Taylor, H.A. Wallweber, D.K. Sasmal, J. Huang, J.M. Kim, I. Mellman, et al., T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition. Science 355(6332), 1428–1433 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. L.B. John, M.H. Kershaw, P.K. Darcy, Blockade of PD-1 immunosuppression boosts CAR T-cell therapy. Oncoimmunology 2(10), e26286 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  25. S.L. Maude, G.E. Hucks, A.E. Self, M.K. Talekar, D.T. Teachey, D. Baniewicz, C. Callahan, V. Gonzalez, F. Nazimuddin, M. Gupta, et al., The effect of pembrolizumab in combination with CD19-targeted chimeric antigen receptor (CAR) T cells in relapsed acute lymphoblastic leukemia (ALL). J. Clin. Oncol. 35 (2017)

  26. E.A. Chong, C. Alanio, J. Svoboda, S.D. Nasta, D.J. Landsburg, S.F. Lacey, M. Ruella, S. Bhattacharyya, E.J. Wherry, S.J. Schuster, Pembrolizumab for B-cell lymphomas relapsing after or refractory to CD19-directed CAR T-cell therapy. Blood 139(7), 1026–1038 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. N. Wang, X. Hu, W. Cao, C. Li, Y. Xiao, Y. Cao, C. Gu, S. Zhang, L. Chen, J. Cheng, et al., Efficacy and safety of CAR19/22 T-cell cocktail therapy in patients with refractory/relapsed B-cell malignancies. Blood 135(1), 17–27 (2020)

    Article  PubMed  Google Scholar 

  28. B.D. Cheson, R.I. Fisher, S.F. Barrington, F. Cavalli, L.H. Schwartz, E. Zucca, T.A. Lister, A.L. Alliance, Lymphoma G, Eastern Cooperative Oncology G et al., Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J. Clin. Oncol. 32(27), 3059–3068 (2014)

    Article  Google Scholar 

  29. M. Pennisi, T. Jain, B.D. Santomasso, E. Mead, K. Wudhikarn, M.L. Silverberg, Y. Batlevi, R. Shouval, S.M. Devlin, C. Batlevi, et al., Comparing CAR T-cell toxicity grading systems: application of the ASTCT grading system and implications for management. Blood Adv. 4(4), 676–686 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Y. Lou, C. Chen, X. Long, J. Gu, M. Xiao, D. Wang, X. Zhou, T. Li, Z. Hong, C. Li, et al., Detection and quantification of chimeric antigen receptor transgene copy number by droplet digital PCR versus real-time PCR. J. Mol. Diagn. 22(5), 699–707 (2020)

    Article  CAS  PubMed  Google Scholar 

  31. B. Coiffier, E. Lepage, J. Briere, R. Herbrecht, H. Tilly, R. Bouabdallah, P. Morel, E. Van Den Neste, G. Salles, P. Gaulard, et al., CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N. Engl. J. Med. 346(4), 235–242 (2002)

    Article  CAS  PubMed  Google Scholar 

  32. J.W. Friedberg, Relapsed/refractory diffuse large B-cell lymphoma. Hematology Am. Soc. Hematol. Educ. Program 2011, 498–505 (2011)

    Article  PubMed  Google Scholar 

  33. S. Rafiq, R.J. Brentjens, Tumors evading CARs-the chase is on. Nat. Med. 24(10), 1492–1493 (2018)

    Article  CAS  PubMed  Google Scholar 

  34. M.C. Zhang, S. Tian, D. Fu, L. Wang, S. Cheng, H.M. Yi, X.F. Jiang, Q. Song, Y. Zhao, Y. He, et al., Genetic subtype-guided immunochemotherapy in diffuse large B cell lymphoma: the randomized GUIDANCE-01 trial. Cancer Cell 41(10), 1705–1716 e1705 (2023)

    Article  CAS  PubMed  Google Scholar 

  35. A. Chow, K. Perica, C.A. Klebanoff, J.D. Wolchok, Clinical implications of T cell exhaustion for cancer immunotherapy. Nat. Rev. Clin. Oncol. 19(12), 775–790 (2022)

    Article  PubMed  Google Scholar 

  36. A. Pedoeem, I. Azoulay-Alfaguter, M. Strazza, G.J. Silverman, A. Mor, Programmed death-1 pathway in cancer and autoimmunity. Clin. Immunol. 153(1), 145–152 (2014)

    Article  CAS  PubMed  Google Scholar 

  37. P.C. Tumeh, C.L. Harview, J.H. Yearley, I.P. Shintaku, E.J. Taylor, L. Robert, B. Chmielowski, M. Spasic, G. Henry, V. Ciobanu, et al., PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515(7528), 568–571 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. E.K. Moon, L.C. Wang, D.V. Dolfi, C.B. Wilson, R. Ranganathan, J. Sun, V. Kapoor, J. Scholler, E. Pure, M.C. Milone, et al., Multifactorial T-cell hypofunction that is reversible can limit the efficacy of chimeric antigen receptor-transduced human T cells in solid tumors. Clin. Cancer Res. 20(16), 4262–4273 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. E.A. Chong, J.J. Melenhorst, S.F. Lacey, D.E. Ambrose, V. Gonzalez, B.L. Levine, C.H. June, S.J. Schuster, PD-1 blockade modulates chimeric antigen receptor (CAR)-modified T cells: refueling the CAR. Blood 129(8), 1039–1041 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Y. Cao, W. Lu, R. Sun, X. Jin, L. Cheng, X. He, L. Wang, T. Yuan, C. Lyu, M. Zhao, Anti-CD19 chimeric antigen receptor T cells in combination with nivolumab are safe and effective against relapsed/refractory B-cell non-hodgkin lymphoma. Front. Oncol. 9, 767 (2019)

    Article  PubMed  PubMed Central  Google Scholar 

  41. L.J. Nastoupil, C.K. Chin, J.R. Westin, N.H. Fowler, F. Samaniego, X. Cheng, M. Mcj, Z. Wang, F. Chu, L. Dsouza, et al., Safety and activity of pembrolizumab in combination with rituximab in relapsed or refractory follicular lymphoma. Blood Adv. 6(4), 1143–1151 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. B. Diskin, S. Adam, M.F. Cassini, G. Sanchez, M. Liria, B. Aykut, C. Buttar, E. Li, B. Sundberg, R.D. Salas, et al., PD-L1 engagement on T cells promotes self-tolerance and suppression of neighboring macrophages and effector T cells in cancer. Nat. Immunol. 21(4), 442–454 (2020)

    Article  CAS  PubMed  Google Scholar 

  43. D.S. Thommen, V.H. Koelzer, P. Herzig, A. Roller, M. Trefny, S. Dimeloe, A. Kiialainen, J. Hanhart, C. Schill, C. Hess, et al., A transcriptionally and functionally distinct PD-1(+) CD8(+) T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade. Nat. Med. 24(7), 994–1004 (2018)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. M. Yi, X. Zheng, M. Niu, S. Zhu, H. Ge, K. Wu, Combination strategies with PD-1/PD-L1 blockade: current advances and future directions. Mol. Cancer 21(1), 28 (2022)

    Article  PubMed  PubMed Central  Google Scholar 

  45. N. Patsoukis, Q. Wang, L. Strauss, V.A. Boussiotis, Revisiting the PD-1 pathway. Sci. Adv. 6(38), eabd2712 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. A.M. Lesokhin, S.M. Ansell, P. Armand, E.C. Scott, A. Halwani, M. Gutierrez, M.M. Millenson, A.D. Cohen, S.J. Schuster, D. Lebovic, et al., Nivolumab in patients with relapsed or refractory hematologic malignancy: preliminary results of a phase Ib study. J. Clin. Oncol. 34(23), 2698–2704 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. M.J. Frigault, P. Armand, R.A. Redd, E. Jeter, R.W. Merryman, K.C. Coleman, A.F. Herrera, P. Dahi, Y. Nieto, A.S. LaCasce, et al., PD-1 blockade for diffuse large B-cell lymphoma after autologous stem cell transplantation. Blood Adv. 4(1), 122–126 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. A. Heczey, C.U. Louis, B. Savoldo, O. Dakhova, A. Durett, B. Grilley, H. Liu, M.F. Wu, Z. Mei, A. Gee, et al., CAR T cells administered in combination with lymphodepletion and PD-1 inhibition to patients with neuroblastoma. Mol. Ther. 25(9), 2214–2224 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. W. Sang, X. Wang, H. Geng, T. Li, D. Li, B. Zhang, Y. Zhou, X. Song, C. Sun, D. Yan, et al., Anti-PD-1 therapy enhances the efficacy of CD30-directed chimeric antigen receptor T cell therapy in patients with relapsed/refractory CD30+ lymphoma. Front. Immunol. 13, 858021 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. J. Mu, H. Deng, C. Lyu, J. Yuan, Q. Li, J. Wang, Y. Jiang, Q. Deng, J. Shen, Efficacy of programmed cell death 1 inhibitor maintenance therapy after combined treatment with programmed cell death 1 inhibitors and anti-CD19-chimeric antigen receptor T cells in patients with relapsed/refractory diffuse large B-cell lymphoma and high tumor burden. Hematol. Oncol. 41(2), 275–284 (2023)

    Article  CAS  PubMed  Google Scholar 

  51. U. Jaeger, N. Worel, J.P. McGuirk, P.A. Riedell, I. Fleury, Y. Du, X. Han, D. Pearson, S. Redondo, E.K. Waller, Safety and efficacy of tisagenlecleucel plus pembrolizumab in patients with r/r DLBCL: phase 1b PORTIA study results. Blood Adv. 7(11), 2283–2286 (2023)

    Article  CAS  PubMed  Google Scholar 

  52. C.A. Jacobson, J.R. Westin, D.B. Miklos, A.F. Herrera, J. Lee, J. Seng, J.M. Rossi, J. Sun, J. Dong, Z.J. Roberts, et al., Phase 1/2 primary analysis of ZUMA-6: axicabtagene ciloleucel (Axi-Cel) in combination with atezolizumab (Atezo) for the treatment of patients (Pts) with refractory diffuse large B cell lymphoma (DLBCL). Cancer Res. 80(16), CT055 (2020)

    Article  Google Scholar 

  53. P. Tsirigotis, B.N. Savani, A. Nagler, Programmed death-1 immune checkpoint blockade in the treatment of hematological malignancies. Ann. Med. 48(6), 428–439 (2016)

    Article  CAS  PubMed  Google Scholar 

  54. P. Otahal, D. Prukova, V. Kral, M. Fabry, P. Vockova, L. Lateckova, M. Trneny, P. Klener, Lenalidomide enhances antitumor functions of chimeric antigen receptor modified T cells. Oncoimmunology 5(4), e1115940 (2016)

    Article  PubMed  Google Scholar 

  55. J.A. Fraietta, K.A. Beckwith, P.R. Patel, M. Ruella, Z. Zheng, D.M. Barrett, S.F. Lacey, J.J. Melenhorst, S.E. McGettigan, D.R. Cook, et al., Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia. Blood 127(9), 1117–1127 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. X. Yang, Q. Yu, H. Xu, J. Zhou, Upregulation of CD22 by chidamide promotes CAR T cells functionality. Sci. Rep. 11(1), 20637 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. R. Bansal, R. Reshef, Revving the CAR - combination strategies to enhance CAR T cell effectiveness. Blood Rev. 45, 100695 (2021)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank all the patients who participated in this study and their families, Wuhan Biotechnology Co., Ltd. and our colleagues for their support.

Funding

This work was supported by grants from the National High Technology Research and Development Program of China (Grant 2021YFA1101504).

Author information

Author notes

  1. Xiangke Xin and Xiaojian Zhu are co-first authors of this manuscript.

Authors and Affiliations

  1. Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, P. R. China

    Xiangke Xin, Xiaojian Zhu, Yang Yang, Na Wang, Jue Wang, Jinhuan Xu, Jia Wei, Liang Huang, Miao Zheng, Yi Xiao, Chunrui Li, Yang Cao, Fankai Meng, Lijun Jiang & Yicheng Zhang

  2. Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, 430030, P. R. China

    Xiaojian Zhu, Yang Yang, Na Wang, Jue Wang, Jinhuan Xu, Jia Wei, Liang Huang, Miao Zheng, Yi Xiao, Chunrui Li, Yang Cao, Fankai Meng, Lijun Jiang & Yicheng Zhang

Authors
  1. Xiangke Xin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaojian Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yang Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Na Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jue Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jinhuan Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jia Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Liang Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Miao Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yi Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Chunrui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yang Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Fankai Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Lijun Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Yicheng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YZ and LJ conceived and designed the study. XZ revised the manuscript for submission. XZ, YY, NW, JW, JX, JW, LH, MZ, CL, YX, FM, YC, LJ, and YZ enrolled patients and provided patient care; XX collected and analyzed data and wrote the manuscript. All authors contributed to the article and approved the submitted version.

Corresponding authors

Correspondence to Lijun Jiang or Yicheng Zhang.

Ethics declarations

Ethical approval

The study was approved by the institutional review board of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. The patients signed written informed consent to participate in this study.

Conflict of interest

The authors declare that there is no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xin, X., Zhu, X., Yang, Y. et al. Efficacy of programmed cell death 1 inhibitor maintenance after chimeric antigen receptor T cells in patients with relapsed/refractory B-cell non-Hodgkin-lymphoma. Cell Oncol. (2024). https://doi.org/10.1007/s13402-024-00940-y

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s13402-024-00940-y

Keywords

Search

Navigation