From Stem Cell Transplantation to CAR-T Therapy in Relapse-Refractory Diffuse Large B-Cell Lymphoma
Main Article Content
Abstract
Diffuse large B-cell lymphoma is a highly curable disease when complete remission after immunochemotherapy is achieved. Despite a high complete remission rate, which is a prerequisite for a cure, 20–40% of patients will relapse or fail first-line therapy. Salvage chemotherapy followed by intensification with autologous stem cell transplant (ASCT) has been established as a curative treatment for relapsed chemosensitive patients under 60 years of age. The results have been somewhat disappointing, with less than 50% of patients being eligible for transplant and relapse posttransplant ranging from 60–40%. Improvements have been made with new drugs in development, immunoconjugate bispecific monoclonal antibodies, and chimeric antigen receptor technology (CAR-T). A more precise evaluation of prognostic factors with PET scans and other biological factors during treatment will allow for the design of new treatment strategies. The exceptional response rate in phase 2 achieved with the three available CARTs has now been confirmed with a longer follow-up period. At 2 years, the overall survival (OS) expectancy is 50% with a plateau on the curves. Three randomized studies compared CARTs to the standard of care with ASCT and demonstrated the superiority of CARTs. Despite this superiority, the relapse rate remains 50%, which is significantly better than the standard of care. However, major improvements in OS have not yet been achieved. A clearer definition of eligible patients should also take into account their interim pet-scan, metabolic tumour volume, relation with Ct DNA with follow-up of minimal residual disease.
Keywords:
Lymphoma, diffuse large cell, stem cell transplantation, PET scan, relapse, CAR-T, immunochemotherapy
Article Details
How to Cite
GISSELBRECHT, Christian; NESTE, Eric Van Den.
From Stem Cell Transplantation to CAR-T Therapy in Relapse-Refractory Diffuse Large B-Cell Lymphoma.
Medical Research Archives, [S.l.], v. 10, n. 8, aug. 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3014>. Date accessed: 05 nov. 2024.
doi: https://doi.org/10.18103/mra.v10i8.3014.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Sehn LH, Salles G. Diffuse Large B-Cell Lymphoma. The New England journal of medicine 2021; 384(9): 842-58.
2. Gisselbrecht C, Van Den Neste E. How I manage patients with relapsed/refractory diffuse large B cell lymphoma. British journal of haematology 2018; 182(5): 633-43.
3. Gisselbrecht C, Schmitz N, Mounier N, et al. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2012; 30(36): 4462-9.
4. Crump M, Kuruvilla J, Couban S, et al. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2014; 32(31): 3490-6.
5. International Non-Hodgkin's Lymphoma Prognostic Factors P. A predictive model for aggressive non-Hodgkin's lymphoma. The New England journal of medicine 1993; 329(14): 987-94.
6. Ruppert AS, Dixon JG, Salles G, et al. International prognostic indices in diffuse large B-cell lymphoma: a comparison of IPI, R-IPI, and NCCN-IPI. Blood 2020; 135(23): 2041-8.
7. Schmitz N, Zeynalova S, Nickelsen M, et al. CNS International Prognostic Index: A Risk Model for CNS Relapse in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2016; 34(26): 3150-6.
8. Lenz G, Wright G, Dave SS, et al. Stromal gene signatures in large-B-cell lymphomas. The New England journal of medicine 2008; 359(22): 2313-23.
9. Wright GW, Huang DW, Phelan JD, et al. A Probabilistic Classification Tool for Genetic Subtypes of Diffuse Large B Cell Lymphoma with Therapeutic Implications. Cancer cell 2020; 37(4): 551-68 e14.
10. Chapuy B, Stewart C, Dunford AJ, et al. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nature medicine 2018; 24(5): 679-90.
11. Sesques P, Johnson NA. Approach to the diagnosis and treatment of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. Blood 2017; 129(3): 280-8.
12. Wang L, Li LR, Young KH. New agents and regimens for diffuse large B cell lymphoma. Journal of hematology & oncology 2020; 13(1): 175.
13. Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. The New England journal of medicine 2022; 386(4): 351-63.
14. Van Den Neste E, Schmitz N, Mounier N, et al. Outcomes of diffuse large B-cell lymphoma patients relapsing after autologous stem cell transplantation: an analysis of patients included in the CORAL study. Bone marrow transplantation 2017; 52(2): 216-21.
15. Crump M NS, Farooq U, et al. . Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800-1808. Blood 2018; 131(5): 587-8.
16. van Kampen RJ, Canals C, Schouten HC, et al. Allogeneic stem-cell transplantation as salvage therapy for patients with diffuse large B-cell non-Hodgkin's lymphoma relapsing after an autologous stem-cell transplantation: an analysis of the European Group for Blood and Marrow Transplantation Registry. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2011; 29(10): 1342-8.
17. Robinson SP, Boumendil A, Finel H, et al. Autologous stem cell transplantation for relapsed/refractory diffuse large B-cell lymphoma: efficacy in the rituximab era and comparison to first allogeneic transplants. A report from the EBMT Lymphoma Working Party. Bone marrow transplantation 2016; 51(3): 365-71.
18. Hamadani M, Gopal AK, Pasquini M, et al. Allogeneic transplant and CAR-T therapy after autologous transplant failure in DLBCL: a noncomparative cohort analysis. Blood advances 2022; 6(2): 486-94.
19. Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene Ciloleucel CAR-T-Cell Therapy in Refractory Large B-Cell Lymphoma. The New England journal of medicine 2017; 377(26): 2531-44.
20. Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. The New England journal of medicine 2019; 380(1): 45-56.
21. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet 2020; 396(10254): 839-52.
22. Nastoupil LJ, Jain MD, Feng L, et al. Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR-T Consortium. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2020; 38(27): 3119-28.
23. Jacobson CA, Hunter BD, Redd R, et al. Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2020; 38(27): 3095-106.
24. Neelapu SS, Locke FL, Bartlett NL, et al. Comparison of 2-year outcomes with CAR-T cells (ZUMA-1) vs salvage chemotherapy in refractory large B-cell lymphoma. Blood advances 2021; 5(20): 4149-55.
25. Maziarz RT, Zhang J, Yang H, et al. Indirect comparison of tisagenlecleucel and historical treatments for relapsed/refractory diffuse large B-cell lymphoma. Blood advances 2022; 6(8): 2536-47.
26. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. The New England journal of medicine 2022; 386(7):640-654.
27. Kamdar M, Solomon SR, Arnason JE, et al. Lisocabtagene Maraleucel (liso-cel), a CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy, Versus Standard of Care (SOC) with Salvage Chemotherapy (CT) Followed By Autologous Stem Cell Transplantation (ASCT) As Second-Line (2L) Treatment in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): Results from the Randomized Phase 3 Transform. Lancet 2022; 399: 2294–308
28. Bishop MR, Dickinson M, Purtill D, et al. Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma. The New England journal of medicine 2022; 386(7):629-639
29. Shah NN, Ahn KW, Litovich C, et al. Is autologous transplant in relapsed DLBCL patients achieving only a PET+ PR appropriate in the CAR-T-cell era? Blood 2021; 137(10): 1416-23.
30. Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2010; 28(27): 4184-90.
31. Shadman M, Pasquini MC, Ahn KW, et al. Autologous Transplant versus Chimeric Antigen Receptor T-cell Therapy for Relapsed DLBCL in Partial Remission. Blood 2022; 3;139(9):1330-133.
32. Vercellino L, Cottereau AS, Casasnovas O, et al. High total metabolic tumor volume at baseline predicts survival independent of response to therapy. Blood 2020; 135(16): 1396-405.
33. Vercellino L, Di Blasi R, Kanoun S, et al. Predictive factors of early progression after CAR-T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma. Blood advances 2020; 4(22): 5607-15.
34. Barrington SF, Meignan M. Time to Prepare for Risk Adaptation in Lymphoma by Standardizing Measurement of Metabolic Tumor Burden. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2019; 60(8): 1096-102.
35. Kuhnl A, Roddie C, Kirkwood AA, et al. Early FDG-PET response predicts CAR-T failure in large B-cell lymphoma. Blood advances 2022; 6(1): 321-6.
36. Sesques P, Tordo J, Ferrant E, et al. Prognostic Impact of 18F-FDG PET/CT in Patients With Aggressive B-Cell Lymphoma Treated With Anti-CD19 Chimeric Antigen Receptor T Cells. Clinical nuclear medicine 2021; 46(8): 627-34.
37. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2014; 32(27): 3059-68.
38. Eertink JJ, Burggraaff CN, Heymans MW, et al. Optimal timing and criteria of interim PET in DLBCL: a comparative study of 1692 patients. Blood advances 2021; 5(9): 2375-84.
39. Gisselbrecht C. Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphoma: Standard of Care After the PETAL Study? Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2018. Journal of Clinical Oncology 2018; 36 (32): 3272-3273.
40. Kurtz DM, Scherer F, Jin MC, et al. Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2018; 36(28): 2845-53.
41. Meriranta L, Alkodsi A, Pasanen A, et al. Molecular features encoded in the ctDNA reveal heterogeneity and predict outcome in high-risk aggressive B-cell lymphoma. Blood 2022; 139(12): 1863-77.
42. Lulla PD. CAR-T cells and autologous transplantation can coexist for DLBCL. Blood 2022; 139(9): 1266-7.
2. Gisselbrecht C, Van Den Neste E. How I manage patients with relapsed/refractory diffuse large B cell lymphoma. British journal of haematology 2018; 182(5): 633-43.
3. Gisselbrecht C, Schmitz N, Mounier N, et al. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2012; 30(36): 4462-9.
4. Crump M, Kuruvilla J, Couban S, et al. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2014; 32(31): 3490-6.
5. International Non-Hodgkin's Lymphoma Prognostic Factors P. A predictive model for aggressive non-Hodgkin's lymphoma. The New England journal of medicine 1993; 329(14): 987-94.
6. Ruppert AS, Dixon JG, Salles G, et al. International prognostic indices in diffuse large B-cell lymphoma: a comparison of IPI, R-IPI, and NCCN-IPI. Blood 2020; 135(23): 2041-8.
7. Schmitz N, Zeynalova S, Nickelsen M, et al. CNS International Prognostic Index: A Risk Model for CNS Relapse in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2016; 34(26): 3150-6.
8. Lenz G, Wright G, Dave SS, et al. Stromal gene signatures in large-B-cell lymphomas. The New England journal of medicine 2008; 359(22): 2313-23.
9. Wright GW, Huang DW, Phelan JD, et al. A Probabilistic Classification Tool for Genetic Subtypes of Diffuse Large B Cell Lymphoma with Therapeutic Implications. Cancer cell 2020; 37(4): 551-68 e14.
10. Chapuy B, Stewart C, Dunford AJ, et al. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nature medicine 2018; 24(5): 679-90.
11. Sesques P, Johnson NA. Approach to the diagnosis and treatment of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. Blood 2017; 129(3): 280-8.
12. Wang L, Li LR, Young KH. New agents and regimens for diffuse large B cell lymphoma. Journal of hematology & oncology 2020; 13(1): 175.
13. Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. The New England journal of medicine 2022; 386(4): 351-63.
14. Van Den Neste E, Schmitz N, Mounier N, et al. Outcomes of diffuse large B-cell lymphoma patients relapsing after autologous stem cell transplantation: an analysis of patients included in the CORAL study. Bone marrow transplantation 2017; 52(2): 216-21.
15. Crump M NS, Farooq U, et al. . Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800-1808. Blood 2018; 131(5): 587-8.
16. van Kampen RJ, Canals C, Schouten HC, et al. Allogeneic stem-cell transplantation as salvage therapy for patients with diffuse large B-cell non-Hodgkin's lymphoma relapsing after an autologous stem-cell transplantation: an analysis of the European Group for Blood and Marrow Transplantation Registry. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2011; 29(10): 1342-8.
17. Robinson SP, Boumendil A, Finel H, et al. Autologous stem cell transplantation for relapsed/refractory diffuse large B-cell lymphoma: efficacy in the rituximab era and comparison to first allogeneic transplants. A report from the EBMT Lymphoma Working Party. Bone marrow transplantation 2016; 51(3): 365-71.
18. Hamadani M, Gopal AK, Pasquini M, et al. Allogeneic transplant and CAR-T therapy after autologous transplant failure in DLBCL: a noncomparative cohort analysis. Blood advances 2022; 6(2): 486-94.
19. Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene Ciloleucel CAR-T-Cell Therapy in Refractory Large B-Cell Lymphoma. The New England journal of medicine 2017; 377(26): 2531-44.
20. Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. The New England journal of medicine 2019; 380(1): 45-56.
21. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet 2020; 396(10254): 839-52.
22. Nastoupil LJ, Jain MD, Feng L, et al. Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR-T Consortium. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2020; 38(27): 3119-28.
23. Jacobson CA, Hunter BD, Redd R, et al. Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2020; 38(27): 3095-106.
24. Neelapu SS, Locke FL, Bartlett NL, et al. Comparison of 2-year outcomes with CAR-T cells (ZUMA-1) vs salvage chemotherapy in refractory large B-cell lymphoma. Blood advances 2021; 5(20): 4149-55.
25. Maziarz RT, Zhang J, Yang H, et al. Indirect comparison of tisagenlecleucel and historical treatments for relapsed/refractory diffuse large B-cell lymphoma. Blood advances 2022; 6(8): 2536-47.
26. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. The New England journal of medicine 2022; 386(7):640-654.
27. Kamdar M, Solomon SR, Arnason JE, et al. Lisocabtagene Maraleucel (liso-cel), a CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy, Versus Standard of Care (SOC) with Salvage Chemotherapy (CT) Followed By Autologous Stem Cell Transplantation (ASCT) As Second-Line (2L) Treatment in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): Results from the Randomized Phase 3 Transform. Lancet 2022; 399: 2294–308
28. Bishop MR, Dickinson M, Purtill D, et al. Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma. The New England journal of medicine 2022; 386(7):629-639
29. Shah NN, Ahn KW, Litovich C, et al. Is autologous transplant in relapsed DLBCL patients achieving only a PET+ PR appropriate in the CAR-T-cell era? Blood 2021; 137(10): 1416-23.
30. Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2010; 28(27): 4184-90.
31. Shadman M, Pasquini MC, Ahn KW, et al. Autologous Transplant versus Chimeric Antigen Receptor T-cell Therapy for Relapsed DLBCL in Partial Remission. Blood 2022; 3;139(9):1330-133.
32. Vercellino L, Cottereau AS, Casasnovas O, et al. High total metabolic tumor volume at baseline predicts survival independent of response to therapy. Blood 2020; 135(16): 1396-405.
33. Vercellino L, Di Blasi R, Kanoun S, et al. Predictive factors of early progression after CAR-T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma. Blood advances 2020; 4(22): 5607-15.
34. Barrington SF, Meignan M. Time to Prepare for Risk Adaptation in Lymphoma by Standardizing Measurement of Metabolic Tumor Burden. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2019; 60(8): 1096-102.
35. Kuhnl A, Roddie C, Kirkwood AA, et al. Early FDG-PET response predicts CAR-T failure in large B-cell lymphoma. Blood advances 2022; 6(1): 321-6.
36. Sesques P, Tordo J, Ferrant E, et al. Prognostic Impact of 18F-FDG PET/CT in Patients With Aggressive B-Cell Lymphoma Treated With Anti-CD19 Chimeric Antigen Receptor T Cells. Clinical nuclear medicine 2021; 46(8): 627-34.
37. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2014; 32(27): 3059-68.
38. Eertink JJ, Burggraaff CN, Heymans MW, et al. Optimal timing and criteria of interim PET in DLBCL: a comparative study of 1692 patients. Blood advances 2021; 5(9): 2375-84.
39. Gisselbrecht C. Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphoma: Standard of Care After the PETAL Study? Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2018. Journal of Clinical Oncology 2018; 36 (32): 3272-3273.
40. Kurtz DM, Scherer F, Jin MC, et al. Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2018; 36(28): 2845-53.
41. Meriranta L, Alkodsi A, Pasanen A, et al. Molecular features encoded in the ctDNA reveal heterogeneity and predict outcome in high-risk aggressive B-cell lymphoma. Blood 2022; 139(12): 1863-77.
42. Lulla PD. CAR-T cells and autologous transplantation can coexist for DLBCL. Blood 2022; 139(9): 1266-7.