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Commentary

End points in clinical trials in diffuse large B-cell lymphoma: time for more dialogue?

ORCID Icon, , , , , , , , , , , , & show all
Received 13 Oct 2023, Accepted 16 May 2024, Published online: 18 Jun 2024

References

  • Richardson NC, Kasamon Y, Pazdur R, et al. The saga of PI3K inhibitors in haematological malignancies: survival is the ultimate safety endpoint. Lancet Oncol. 2022;23(5):563–566. doi:10.1016/S1470-2045(22)00200-5
  • FDA Guidance for Industry. Clinical trial endpoints for the approval of cancer drugs and biologics. December 2018. Available from: www.fda.gov/media/71195/download
  • Dabisch I, Dethling J, Dintsios CM, et al. Patient relevant endpoints in oncology: current issues in the context of early benefit assessment in Germany. Health Econ Rev. 2014;4(1):2. doi:10.1186/2191-1991-4-2
  • ICH Harmonised Guideline. E8(R1) General considerations for clinical studies. [ updated 2021 Oct 06]. Available from: www.ema.europa.eu/en/documents/regulatory-procedural-guideline/ich-guideline-e8-r1-general-considerations-clinical-studies_en.pdf
  • ICH Harmonised Guideline. E9(R1) Addendum on estimands and sensitivity analysis in clinical trials. [ updated 2019 Nov 20]. Available from: https://database.ich.org/sites/default/files/E9-R1_Step4_Guideline_2019_1203.pdf
  • Degtyarev E, Zhang Y, Sen K, et al. Estimands and the patient journey: addressing the right question in oncology clinical trials. JCO Precis Oncol. 2019;3:1–10. doi:10.1200/PO.18.00381
  • Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(4):235–242. doi:10.1056/NEJMoa011795
  • Coiffier B, Thieblemont C, Van Den Neste E, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood. 2010;116(12):2040–2045. doi:10.1182/blood-2010-03-276246
  • Younes A, Sehn LH, Johnson P, et al. Randomized Phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non-germinal center B-cell diffuse large B-cell lymphoma. J Clin Oncol. 2019;37(15):1285–1295. doi:10.1200/JCO.18.02403
  • Bartlett NL, Wilson WH, Jung SH, et al. Dose-adjusted EPOCH-R compared with R-CHOP as frontline therapy for diffuse large B-cell lymphoma: clinical outcomes of the Phase III intergroup trial Alliance/CALGB 50303. J Clin Oncol. 2019;37(21):1790–1799. doi:10.1200/JCO.18.01994
  • ClinicalTrials.gov. Study to compare axicabtagene ciloleucel with standard of care therapy as first-line treatment in participants with high-risk large B-cell lymphoma (ZUMA-23). [ Last updated: 2024 Feb 22; accessed: 2024 Feb 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT05605899
  • Seymour JF, Pfreundschuh M, Trněný M. R-CHOP with or without bevacizumab in patients with previously untreated diffuse large B-cell lymphoma: final MAIN study outcomes. Haematologica. 2014;99(8):1343–1349. doi:10.3324/haematol.2013.100818
  • ClinicalTrials.gov. A study to evaluate change in disease activity of subcutaneous (sc) epcoritamab combined with intravenous and oral rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP) or R-CHOP in adult participants with newly diagnosed diffuse large B-cell lymphoma (DLBCL) (EPCORE DLBCL-2). [ Last updated: 2024 Feb 23; accessed: 2024 Feb 23]. Available from: https://clinicaltrials.gov/study/NCT05578976
  • Vitolo U, Trněný M, Belada D, et al. Obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated diffuse large B-cell lymphoma. J Clin Oncol. 2017;35(31):3529–3537. doi:10.1200/JCO.2017.73.3402
  • Nowakowski GS, Chiappella A, Gascoyne RD, et al. ROBUST: a Phase III study of lenalidomide plus R-CHOP versus placebo plus R-CHOP in previously untreated patients with ABC-type diffuse large B-cell lymphoma. J Clin Oncol. 2021;39(12):1317–1328. doi:10.1200/JCO.20.01366
  • Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma. N Engl J Med. 2022;386(4):351–363. doi:10.1056/NEJMoa2115304
  • ClinicalTrials.gov. A randomized, multicenter, Phase III trial comparing treatment with R-mini-CHOP with R-mini-CHP + polatuzumab vedotin in patients with diffuse large cell B cell lymphoma (POLAR BEAR). [ Last updated: 2024 Feb 13; accessed: 2024 Feb 23]. Available from: https://clinicaltrials.gov/study/NCT04332822
  • ClinicalTrials.gov. Tafasitamab + lenalidomide + R-CHOP versus R-CHOP in newly diagnosed high-intermediate and high risk DLBCL patients (frontMIND). [ Last updated: 2023 Nov 29; accessed: 2024 Feb 23]. Available from: www.clinicaltrials.gov/ct2/show/NCT04824092
  • Bishop MR, Dickinson M, Purtill D, et al. Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma. N Engl J Med. 2022;386(7):629–639. doi:10.1056/NEJMoa2116596
  • Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386(7):640–654. doi:10.1056/NEJMoa2116133
  • Kamdar M, Solomon SR, Arnason JE, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, Phase III trial. Lancet. 2022;399(10343):2294–2308. doi:10.1016/S0140-6736(22)00662-6
  • Belada D, Georgiev P, Dakhil S, et al. Pixantrone-rituximab versus gemcitabine-rituximab in relapsed/refractory aggressive non-hodgkin lymphoma. Future Oncol. 2016;12(15):1759–1768. doi:10.2217/fon-2016-0137
  • ClinicalTrials.gov. Study to evaluate loncastuximab tesirine with rituximab versus immunochemotherapy in participants with relapsed or refractory diffuse large B-cell lymphoma (LOTIS 5). [ Last updated: 2024 Jan 24; accessed: 2024 Feb 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT04384484
  • ClinicalTrials.gov. A study evaluating efficacy and safety of mosunetuzumab in combination with polatuzumab vedotin compared to rituximab in combination with gemcitabine plus oxaliplatin in participants with relapsed or refractory aggressive B-cell non-hodgkin's lymphoma (SUNMO). [ Last updated: 2024 Jan 31; accessed: 2024 Feb 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT05171647
  • ClinicalTrials.gov. A study of rituximab-gemcitabine-dexamethasone-platinum (R-GDP) with or without selinexor in patients with relapsed/refractory diffuse large B-cell lymphoma. [ Last updated: 2023 Oct 03; accessed: 2024 Feb 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT04442022
  • ClinicalTrials.gov. A trial to evaluate the efficacy and safety of tafasitamab with bendamustine (BEN) versus rituximab (RTX) with BEN in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (B-MIND). [ Last updated: 2022 Aug 02; accessed: 2024 Feb 23] https://clinicaltrials.gov/ct2/show/NCT02763319
  • Dang NH, Ogura M, Castaigne S, et al. Randomized, Phase III trial of inotuzumab ozogamicin plus rituximab versus chemotherapy plus rituximab for relapsed/refractory aggressive B-cell non-hodgkin lymphoma. Br J Haematol. 2018;182(4):583–586. doi:10.1111/bjh.14820
  • ClinicalTrials.gov. A Phase III trial of epcoritamab vs investigator's choice chemotherapy in R/R DLBCL (EPCORE DLBCL-1). [ Last updated: 2024 Feb 06; accessed: 2024 Feb 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT04628494
  • ClinicalTrials.gov. A study to evaluate the safety and efficacy of polatuzumab vedotin in combination with rituximab, gemcitabine and oxaliplatin compared to rituximab, gemcitabine and oxaliplatin alone in participants with relapsed or refractory diffuse large B-cell lymphoma (POLARGO). [ Last updated: 2023 Dec 14; accessed: 2024 Feb 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT04182204
  • ClinicalTrials.gov. A Phase III study evaluating glofitamab in combination with gemcitabine + oxaliplatin vs rituximab in combination with gemcitabine + oxaliplatin in participants with relapsed/refractory diffuse large B-cell lymphoma. [ Last updated: 2024 Feb 13; accessed: 2024 Feb 23]. Available from: www.clinicaltrials.gov/ct2/show/NCT04408638
  • ClinicalTrials.gov. Polatuzumab vedotin plus rituximab, ifosfamide, carboplatin and etoposide (Pola-R-ICE) versus R-ICE alone in second line treatment of diffuse large B-cell lymphoma (DLBCL). [ Last updated: 2023 Oct 12; accessed: 2024 Feb 23]. Available from: www.clinicaltrials.gov/ct2/show/NCT04833114
  • Manitz J, Kan-Dobrosky N, Buchner H, et al. Estimands for overall survival in clinical trials with treatment switching in oncology. Pharm Stat. 2022;21(1):150–162. doi:10.1200/pst.2158
  • 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. J Clin Oncol. 2014;32(27):3059–3068. doi:10.1200/JCO.2013.54.8800
  • Cheson BD, Ansell S, Schwartz L, et al. Refinement of the lugano classification lymphoma response criteria in the era of immunomodulatory therapy. Blood. 2016;128(21):2489–2496. doi:10.1182/blood-2016-05-718528
  • Park HJ, Kim KW, Pyo J, et al. Incidence of pseudoprogression during immune checkpoint inhibitor therapy for solid tumors: a systematic review and meta-analysis. Radiology. 2020;297(1):87–96. doi:10.1148/radiol.2020200443
  • Barth M, Xavier AC, Armenian S, et al. Pediatric aggressive mature B-cell lymphomas, version 3.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2022;20(11):1267–1275. doi:10.6004/jnccn.2022.0057
  • Crump M, Neelapu SS, 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. doi:10.1182/blood-2017-03-769620
  • Fojo T, Simon RM. Inappropriate censoring in Kaplan-Meier analyses [comment]. Lancet Oncol. 2021;22(10):1358–1360. doi:10.1016/S1470-2045(21)00473-3
  • FDA Guidance for Industry. Acute Myeloid Leukemia: Developing Drugs and Biological Products for Treatment. October 2022. Available from: www.fda.gov/media/162362/download
  • Pazdur R. Endpoints for assessing drug activity in clinical trials. The Oncol. 2008;13(S2):19–21. doi:10.1634/theoncologist.13-S2-19
  • Clinical Review and Evaluation – YESCARTA. 2022 Apr 01. Available from: www.fda.gov/media/157687/download
  • US Package Insert – YESCARTA. [ revised: Dec 2023]. Available from: www.fda.gov/media/108377/download
  • Riedell PA, Brower J, Nastoupil LJ, et al. A multicenter retrospective analysis of outcomes and toxicities with commercial axicabtagene ciloleucel and tisagenlecleucel for relapsed/refractory aggressive B-cell lymphomas. Oral presentation 52. Presented at: Orlando, FL: 2020 TCT; February 19–23, 2020.
  • Kwon M, Iacoboni G, Reguera JL, et al. Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of relapsed or refractory large B-cell lymphoma in the real world setting in Spain. Blood. 2021;138(Suppl. 1):1742. doi:10.1182/blood-2021-147369
  • Chiappella A, Guidetti A, Dodero A, et al. Real-life CAR-T cell treatment in large B-cell lymphomas indicates that axi-cel and tisa-cel have similar outcomes, but long-term cytopenia is an emerging problem. Blood. 2021;138(Suppl. 1):3867. doi:10.1182/blood-2021-154037
  • Quality of Life of Cancer Patients - EORTC QLQ-C30. Available from: https://qol.eortc.org/questionnaire/eortc-qlq-c30/
  • FACT-Lym (facit.org). Functional Assessment of Cancer Therapy – Lymphoma. Available from: www.facit.org/measures/FACT-Lym
  • Fiero MH, Roydhouse JK, Bhatnagar V, et al. Time to deterioration of symptoms or function using patient-reported outcomes in cancer trials. Lancet Oncol. 2022;23(5):e229–e234. doi:10.1016/S1470-2045(22)00021-3
  • Lawrance R, Degtyarev E, Griffiths P, et al. What is an estimand & how does it relate to quantifying the effect of treatment on patient-reported quality of life outcomes in clinical trials? J Patient RepOutcomes. 2020;4(1):68. doi:10.1186/s41687-020-00218-5
  • Rufibach K. Treatment effect quantification for time-to-event endpoints – Estimands, analysis strategies, and beyond. Pharm Stat. 2019;18:144–164. doi:10.1002/pst.1917
  • Abramson JS, Solomon SR, Arnason JE, et al. Improved quality of life (QOL) with lisocabtagene maraleucel (liso-cel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy, compared with standard of Care (SOC) as second-line (2L) treatment in patients (Pts) with relapsed or refractory (R/R) large B-cell lymphoma (LBCL): results from the Phase III Transform study. Blood. 2021;138(Suppl. 1):3845. doi:10.1182/blood-2021–151611
  • Punt CJ, Buyse M, Köhne CH, et al. Endpoints in adjuvant treatment trials: a systematic review of the literature in colon cancer and proposed definitions for future trials. J Natl Cancer Inst. 2007;99(13):998–1003. doi:10.1093/jnci/djm024
  • Casey M, Degtyarev E, Lechuga MJ, et al. Estimand framework: are we asking the right questions? a case study in the solid tumor setting. Pharm Stat. 2021;20:324–334. doi:10.1002/pst.2079