Effectiveness of tisagenlecleucel versus real-world standard of care in relapsed/refractory follicular lymphoma
Publication: Journal of Comparative Effectiveness Research
Abstract
Aim: To contextualize the effectiveness of tisagenlecleucel versus real-world standard of care (SoC) in relapsed/refractory follicular lymphoma. Materials & methods: A retrospective indirect matched comparison study using data from the phase II ELARA trial and the US Flatiron Health Research Database. Results: Complete response rate was 69.1 versus 17.7% and the overall response rate was 85.6 versus 58.1% in tisagenlecleucel versus SoC, post weighting by odds. For overall survival, an estimated reduction in the risk of death was observed in favor of tisagenlecleucel over SoC. The hazard ratio for progression-free survival was 0.45 (95% CI: 0.26, 0.88), and for time-to-next treatment was 0.34 (95% CI: 0.15, 0.78) with tisagenlecleucel versus SoC. Conclusion: A consistent trend toward improved efficacy end points was observed in favor of tisagenlecleucel versus SoC.
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References
Papers of special note have been highlighted as: • of interest; •• of considerable interest
1.
Fowler NH, Dickinson M, Dreyling M et al. Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase II ELARA trial. Nat. Med. 28(2), 325–332 (2022).
•• Reports the primary efficacy and safety results from ELARA trial of tisagenlecleucel.
2.
Freedman A, Jacobsen E. Follicular lymphoma: 2020 update on diagnosis and management. Am. J. Hematol. 95(3), 316–327 (2020).
3.
Ghielmini M, Vitolo U, Kimby E et al. ESMO guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). Ann. Oncol. 24(3), 561–576 (2013).
4.
Dada R. Diagnosis and management of follicular lymphoma: a comprehensive review. Eur. J. Haematol. 103(3), 152–163 (2019).
5.
Mondello P, Ansell SM. Tazemetostat: a treatment option for relapsed/refractory follicular lymphoma. Expert Opin. Pharmacother. 23(3), 295–301 (2022).
6.
Yared J, Gandhi AB, Nagarajan M et al. Patient-level factors associated with the initial management of older adults diagnosed with follicular lymphoma: a surveillance, epidemiology, and end results-medicare analysis. Clin. Lymphoma Myeloma Leuk. 20(4), e184–e194 (2020).
7.
Federico M, Luminari S, Dondi A et al. R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage follicular lymphoma: results of the FOLL05 trial conducted by the Fondazione Italiana Linfomi. J. Clin. Oncol. 31(12), 1506–1513 (2013).
8.
Zelenetz AD, Gordon LI, Chang JE et al. NCCN Guidelines(R) Insights: B-Cell Lymphomas, Version 5.2021. J. Natl Compr. Canc. Netw. 19(11), 1218–1230 (2021).
9.
Jurinovic V, Kridel R, Staiger AM et al. Clinicogenetic risk models predict early progression of follicular lymphoma after first-line immunochemotherapy. Blood 128(8), 1112–1120 (2016).
10.
Casulo C, Byrtek M, Dawson KL et al. Early relapse of follicular lymphoma after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone defines patients at high risk for death: an analysis from the National LymphoCare Study. J. Clin. Oncol. 33(23), 2516–2522 (2015).
11.
Grillo-Lopez AJ. Zevalin: the first radioimmunotherapy approved for the treatment of lymphoma. Expert Rev. Anticancer Ther. 2(5), 485–493 (2002).
12.
US FDA. FDA approves lenalidomide for follicular and marginal zone lymphoma. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lenalidomide-follicular-and-marginal-zone-lymphoma
13.
US FDA. FDA grants accelerated approval to umbralisib for marginal zone lymphoma and follicular lymphoma. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-umbralisib-marginal-zone-lymphoma-and-follicular-lymphoma
14.
US FDA. FDA granted accelerated approval to tazemetostat for follicular lymphoma. https://www.fda.gov/drugs/fda-granted-accelerated-approval-tazemetostat-follicular-lymphoma
15.
Ollila TA, Olszewski AJ. Chemotherapy-free management of follicular and marginal zone lymphoma. Cancer Manag. Res. 13, 3935–3952 (2021).
16.
Burke JM. Evolving third-line treatment options for follicular lymphoma. Clin. Adv. Hematol. Oncol. 20(6), 394–396 (2022).
17.
Fischer L, Dreyling M. Follicular lymphoma: an update on biology and optimal therapy. Leuk. Lymph. 64(4), 761–775 (2023).
18.
Jacobson CA, Chavez JC, Sehgal AR et al. Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase II trial. Lancet Oncol. 23(1), 91–103 (2022).
19.
ClinicalTrial.Gov. Study to Evaluate the efficacy and safety of JCAR017 in adult subjects with relapsed or refractory indolent B-cell non-Hodgkin lymphoma (NHL) (TRANSCEND FL). https://clinicaltrials.gov/ct2/show/NCT04245839
20.
Budde LE, Sehn LH, Matasar M et al. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase II study. Lancet Oncol. 23(8), 1055–1065 (2022).
21.
Budde LE, Sehn LH, Matasar MJ et al. Mosunetuzumab monotherapy is an effective and well-tolerated treatment option for patients with relapsed/refractory (R/R) follicular lymphoma (FL) who have received ≥2 prior lines of therapy: pivotal results from a Phase I/II study. Blood 138(Suppl. 1), 127–127 (2021).
22.
Kang C. Mosunetuzumab: first approval. Drugs 82(11), 1229–1234 (2022).
23.
US FDA. FDA grants accelerated approval to mosunetuzumab-axgb for relapsed or refractory follicular lymphoma. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-mosunetuzumab-axgb-relapsed-or-refractory-follicular-lymphoma
24.
Prescribing information. KYMRIAH (tisagenlecleucel). https://www.fda.gov/media/107296/download
25.
Summary of product characteristics. KYMRIAH (tisagenlecleucel). https://www.ema.europa.eu/en/documents/product-information/kymriah-epar-product-information_en.pdf
26.
Thieblemont C, Dickinson M, Martinez-Lopez K. Efficacy of tisagenlecleucel in adult patients (Pts) with high-risk relapsed/refractory follicular lymphoma (r/r FL): subgroup analysis of the phase II Elara Study. Presented at: 2021 ASH Annual Meeting and Exposition. GA, USA (2021).
27.
ICH E9(R1). Addendum on estimands and sensitivity analysis in clinical trials to the guideline on statistical principles for clinical trials. https://database.ich.org/sites/default/files/E9-R1_Step4_Guideline_2019_1203.pdf (2019).
28.
Hampson LV, Chu J, Zia A et al. Combining the target trial and estimand frameworks to define the causal estimand: an application using real-world data to contextualize a single-arm trial. Stat. Biopharm. Res. 1-10 (2023).
• Illustrates the application of target trial framework when comparing a single-arm trial with an external control arm to support regulatory submissions.
29.
Hernan MA, Robins JM. Using big data to emulate a target trial when a randomized trial is not available. Am. J. Epidemiol. 183(8), 758–764 (2016).
• Provides a framework for comparative–effectiveness research using big data that makes target trial explicit.
30.
Garcia-Albeniz X, Hsu J, Hernan MA. The value of explicitly emulating a target trial when using real world evidence: an application to colorectal cancer screening. Eur. J. Epidemiol. 32(6), 495–500 (2017).
31.
Flatiron Health database. (2020). https://flatiron.com/real-world-evidence/
32.
Ma X, Long L, Moon S, Adamson BJS, Baxi SS. Comparison of population characteristics in real-world clinical oncology databases in the US: Flatiron Health, SEER, and NPCR. (2020). https://www.medrxiv.org/content/10.1101/2020.03.16.20037143v2
33.
Birnbaum B, Nussbaum N, Seidl-Rathkopf K et al. Model-assisted cohort selection with bias analysis for generating large-scale cohorts from the EHR for oncology research. https://arxiv.org/abs/2001.09765 (2020).
34.
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. 32(27), 3059–3068 (2014).
35.
Tan K, Bryan J, Segal B et al. Emulating control arms for cancer clinical trials using external cohorts created from electronic health record-derived real-world data. Clin. Pharmacol. Ther. 111(1), 168–178 (2022).
36.
Rubin DB. Using propensity scores to help design observational studies: application to the tobacco litigation. Health Serv. Outcomes Res. Meth. 2, 169–188 (2001).
37.
Efron B, Tibshirani RJ. In: An Introduction to the Bootstrap (1st Edition). Chapter 2: The accuracy of a sample mean, Cox DR, Hinkley DV, Reid N, Rubin DB, Silverman BW (Eds). Chapman and Hall/CRC, FL, USA (1994).
38.
Mishra-Kalyani PS, Amiri Kordestani L, Rivera DR et al. External control arms in oncology: current use and future directions. Ann. Oncol. 33(4), 376–383 (2022).
39.
FDA. Considerations for the design and conduct of externally controlled trials for drug and biological products (2023). https://www.fda.gov/media/164960/download
40.
Salles G, Schuster SJ, Dreyling M et al. Efficacy comparison of tisagenlecleucel vs usual care in patients with relapsed or refractory follicular lymphoma. Blood Adv. 6(22), 5835–5843 (2022).
41.
Ghione P, Palomba ML, Patel AR et al. Comparative effectiveness of ZUMA-5 (axi-cel) vs SCHOLAR-5 external control in relapsed/refractory follicular lymphoma. Blood 140(8), 851–860 (2022).
42.
McGough SF, Shamas N, Wang J et al. An external control for mosunetuzumab using real-world data in follicular lymphoma in the third or subsequent lines of systemic therapy. Blood 140(Suppl. 1), 3658–3660 (2022).
43.
Stuart EA. Matching methods for causal inference: a review and a look forward. Stat. Sci. 25(1), 1–21 (2010).
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Received: 27 September 2022
Accepted: 6 April 2023
Published online: 22 June 2023
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Effectiveness of tisagenlecleucel versus real-world standard of care in relapsed/refractory follicular lymphoma. (2023) Journal of Comparative Effectiveness Research. DOI: 10.57264/cer-2022-0173
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