Cost-Effectiveness of Shortening Treatment Duration Based on Interim PET Outcome in Patients With Diffuse Large B-cell Lymphoma

M. J.E. Greuter; J. J. Eertink; PETRA consortium; G. Jongeneel; U. Dührsen; A. Hüttmann; C. Schmitz; P. J. Lugtenburg; S. F. Barrington; N. G. Mikhaeel; L. Ceriani; E. Zucca; R. Carr; T. Györke; C. N. Burggraaff; H. C.W. de Vet; O. S. Hoekstra; J. M. Zijlstra; V. M.H. Coupé

doi:10.1016/j.clml.2021.11.008

Cost-Effectiveness of Shortening Treatment Duration Based on Interim PET Outcome in Patients With Diffuse Large B-cell Lymphoma

M. J.E. Greuter^*
, J. J. Eertink
, PETRA consortium
, G. Jongeneel
, U. Dührsen
, A. Hüttmann
, C. Schmitz
, P. J. Lugtenburg
, S. F. Barrington
, N. G. Mikhaeel
, L. Ceriani
, E. Zucca
, R. Carr
, T. Györke
, C. N. Burggraaff
, H. C.W. de Vet
, O. S. Hoekstra
, J. M. Zijlstra
, V. M.H. Coupé

^*Corresponding author for this work

Hematology

Vrije Universiteit Amsterdam
University Hospital Essen
King's College London
Imaging Institute of Southern Switzerland
Swiss Group for Clinical Cancer Research
Università della Svizzera italiana
University College London
Semmelweis University
Amsterdam UMC

Research output: Contribution to journal › Article › Academic › peer-review

2 Citations (Scopus)

108 Downloads (Pure)

Abstract

Background: Guideline recommendations for diffuse large-B-cell lymphoma (DLBCL) treatment are shifting from long to short treatment duration, although it is still unclear whether shortening treatment duration does not cause any harm. As interim PET (I-PET) has high negative predictive value for progression, we evaluated the cost-effectiveness of shortening treatment duration dependent on I-PET result. Materials and Methods: We developed a Markov cohort model using the PET Re-Analysis (PETRA) database to evaluate a long treatment duration (LTD) strategy, ie 8x R-CHOP or 6x R-CHOP plus 2 R, and a short treatment duration (STD) strategy, ie 6x R-CHOP. Strategies were evaluated separately in I-PET2 positive and I-PET2 negative patients. Outcomes included total costs and quality-adjusted life-years (QALYs) per patient (pp) from a societal perspective. Net monetary benefit (NMB) per strategy was calculated using a willingness-to-pay threshold of €50,000/QALY. Robustness of model predictions was assessed in sensitivity analyses. Results: In I-PET2 positive patients, shortening treatment duration led to 50.4 additional deaths per 1000 patients. The STD strategy was less effective (-0.161 [95%CI: -0.343;0.028] QALYs pp) and less costly (-€2768 [95%CI: -€8420;€1105] pp). Shortening treatment duration was not cost-effective (incremental NMB -€5281). In I-PET2 negative patients, shortening treatment duration led to 5.0 additional deaths per 1000 patients and a minor difference in effectiveness (-0.007 [95%CI: -0.136;0.140] QALY pp). The STD strategy was less costly (-€5807 [95%CI: -€10,724;-€2685] pp) and led to an incremental NMB of €5449, indicating that it is cost-effective to shorten treatment duration. Robustness of these findings was underpinned by deterministic and probabilistic sensitivity analyses. Conclusion: Treatment duration should not be shortened in I-PET2 positive patients whereas it is cost-effective to shorten treatment duration in I-PET2 negative patients.

Original language	English
Pages (from-to)	382-392
Number of pages	11
Journal	Clinical Lymphoma, Myeloma and Leukemia
Volume	22
Issue number	6
Early online date	20 Nov 2021
DOIs	https://doi.org/10.1016/j.clml.2021.11.008
Publication status	Published - 1 Jun 2022

Bibliographical note

Funding Information:
U.D. received research funding from Amgen and Roche and honoraria for advisory boards from Amgen and Roche. P.J.L. received research funding from Takeda, Servier and Roche and honoraria for advisory boards from Takeda, Servier, Roche, Genmab, Celgene, Regeneron and Incyte. S.F.B. is on the speaker's bureau of Takeda and Hofman la Roche and received departmental funding from Bristol Myers Squibb international corporation, Pfizer and Amgen Ltd. J.M.Z. received research funding from Roche and received honoraria for advisory boards from Takeda, Gilead and Roche. All remaining authors have declared no conflict of interest. This work was financially supported by an Alpe d'Huzes/KWF fund provided by the Dutch Cancer Society (# VU 2012–5848). The PETAL trial was supported by grants from the Deutsche Krebshilfe (no. 107592 and no. 110515). Greuter MJE: Conceptualization, Formal analysis, Writing - original draft; Eertink JJ: Conceptualization, Formal analysis; Jongeneel G: Formal analysis; Dührsen U: Data curation; Hüttmann A: Data curation; Schmitz C: Data curation; Lugtenburg PJ: Data curation; Barrington SF: Data curation; Mikhaeel NG: Data curation; Ceriani L: Data curation; Zucca E: Data curation; Carr R: Data curation; Györke T: Data curation; Burggraaff CN: Conceptualization, Formal analysis; de Vet HCW: Conceptualization; Hoekstra OS: Conceptualization; Zijlstra JM: Conceptualization; Coupé VMH: Conceptualization.

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Cite this

Greuter, M. J. E., Eertink, J. J., PETRA consortium, Jongeneel, G., Dührsen, U., Hüttmann, A., Schmitz, C., Lugtenburg, P. J., Barrington, S. F., Mikhaeel, N. G., Ceriani, L., Zucca, E., Carr, R., Györke, T., Burggraaff, C. N., de Vet, H. C. W., Hoekstra, O. S., Zijlstra, J. M., & Coupé, V. M. H. (2022). Cost-Effectiveness of Shortening Treatment Duration Based on Interim PET Outcome in Patients With Diffuse Large B-cell Lymphoma. Clinical Lymphoma, Myeloma and Leukemia, 22(6), 382-392. https://doi.org/10.1016/j.clml.2021.11.008

@article{9701a40daf0a475fa4ebd389ae607ebe,

title = "Cost-Effectiveness of Shortening Treatment Duration Based on Interim PET Outcome in Patients With Diffuse Large B-cell Lymphoma",

abstract = "Background: Guideline recommendations for diffuse large-B-cell lymphoma (DLBCL) treatment are shifting from long to short treatment duration, although it is still unclear whether shortening treatment duration does not cause any harm. As interim PET (I-PET) has high negative predictive value for progression, we evaluated the cost-effectiveness of shortening treatment duration dependent on I-PET result. Materials and Methods: We developed a Markov cohort model using the PET Re-Analysis (PETRA) database to evaluate a long treatment duration (LTD) strategy, ie 8x R-CHOP or 6x R-CHOP plus 2 R, and a short treatment duration (STD) strategy, ie 6x R-CHOP. Strategies were evaluated separately in I-PET2 positive and I-PET2 negative patients. Outcomes included total costs and quality-adjusted life-years (QALYs) per patient (pp) from a societal perspective. Net monetary benefit (NMB) per strategy was calculated using a willingness-to-pay threshold of €50,000/QALY. Robustness of model predictions was assessed in sensitivity analyses. Results: In I-PET2 positive patients, shortening treatment duration led to 50.4 additional deaths per 1000 patients. The STD strategy was less effective (-0.161 [95\%CI: -0.343;0.028] QALYs pp) and less costly (-€2768 [95\%CI: -€8420;€1105] pp). Shortening treatment duration was not cost-effective (incremental NMB -€5281). In I-PET2 negative patients, shortening treatment duration led to 5.0 additional deaths per 1000 patients and a minor difference in effectiveness (-0.007 [95\%CI: -0.136;0.140] QALY pp). The STD strategy was less costly (-€5807 [95\%CI: -€10,724;-€2685] pp) and led to an incremental NMB of €5449, indicating that it is cost-effective to shorten treatment duration. Robustness of these findings was underpinned by deterministic and probabilistic sensitivity analyses. Conclusion: Treatment duration should not be shortened in I-PET2 positive patients whereas it is cost-effective to shorten treatment duration in I-PET2 negative patients.",

author = "Greuter, \{M. J.E.\} and Eertink, \{J. J.\} and \{PETRA consortium\} and G. Jongeneel and U. D{\"u}hrsen and A. H{\"u}ttmann and C. Schmitz and Lugtenburg, \{P. J.\} and Barrington, \{S. F.\} and Mikhaeel, \{N. G.\} and L. Ceriani and E. Zucca and R. Carr and T. Gy{\"o}rke and Burggraaff, \{C. N.\} and \{de Vet\}, \{H. C.W.\} and Hoekstra, \{O. S.\} and Zijlstra, \{J. M.\} and Coup{\'e}, \{V. M.H.\}",

note = "Funding Information: U.D. received research funding from Amgen and Roche and honoraria for advisory boards from Amgen and Roche. P.J.L. received research funding from Takeda, Servier and Roche and honoraria for advisory boards from Takeda, Servier, Roche, Genmab, Celgene, Regeneron and Incyte. S.F.B. is on the speaker's bureau of Takeda and Hofman la Roche and received departmental funding from Bristol Myers Squibb international corporation, Pfizer and Amgen Ltd. J.M.Z. received research funding from Roche and received honoraria for advisory boards from Takeda, Gilead and Roche. All remaining authors have declared no conflict of interest. This work was financially supported by an Alpe d'Huzes/KWF fund provided by the Dutch Cancer Society (\# VU 2012–5848). The PETAL trial was supported by grants from the Deutsche Krebshilfe (no. 107592 and no. 110515). Greuter MJE: Conceptualization, Formal analysis, Writing - original draft; Eertink JJ: Conceptualization, Formal analysis; Jongeneel G: Formal analysis; D{\"u}hrsen U: Data curation; H{\"u}ttmann A: Data curation; Schmitz C: Data curation; Lugtenburg PJ: Data curation; Barrington SF: Data curation; Mikhaeel NG: Data curation; Ceriani L: Data curation; Zucca E: Data curation; Carr R: Data curation; Gy{\"o}rke T: Data curation; Burggraaff CN: Conceptualization, Formal analysis; de Vet HCW: Conceptualization; Hoekstra OS: Conceptualization; Zijlstra JM: Conceptualization; Coup{\'e} VMH: Conceptualization. Publisher Copyright: {\textcopyright} 2021",

year = "2022",

month = jun,

day = "1",

doi = "10.1016/j.clml.2021.11.008",

language = "English",

volume = "22",

pages = "382--392",

number = "6",

}

Greuter, MJE, Eertink, JJ, PETRA consortium, Jongeneel, G, Dührsen, U, Hüttmann, A, Schmitz, C, Lugtenburg, PJ, Barrington, SF, Mikhaeel, NG, Ceriani, L, Zucca, E, Carr, R, Györke, T, Burggraaff, CN, de Vet, HCW, Hoekstra, OS, Zijlstra, JM & Coupé, VMH 2022, 'Cost-Effectiveness of Shortening Treatment Duration Based on Interim PET Outcome in Patients With Diffuse Large B-cell Lymphoma', Clinical Lymphoma, Myeloma and Leukemia, vol. 22, no. 6, pp. 382-392. https://doi.org/10.1016/j.clml.2021.11.008

TY - JOUR

T1 - Cost-Effectiveness of Shortening Treatment Duration Based on Interim PET Outcome in Patients With Diffuse Large B-cell Lymphoma

AU - Greuter, M. J.E.

AU - Eertink, J. J.

AU - PETRA consortium

AU - Jongeneel, G.

AU - Dührsen, U.

AU - Hüttmann, A.

AU - Schmitz, C.

AU - Lugtenburg, P. J.

AU - Barrington, S. F.

AU - Mikhaeel, N. G.

AU - Ceriani, L.

AU - Zucca, E.

AU - Carr, R.

AU - Györke, T.

AU - Burggraaff, C. N.

AU - de Vet, H. C.W.

AU - Hoekstra, O. S.

AU - Zijlstra, J. M.

AU - Coupé, V. M.H.

N1 - Funding Information: U.D. received research funding from Amgen and Roche and honoraria for advisory boards from Amgen and Roche. P.J.L. received research funding from Takeda, Servier and Roche and honoraria for advisory boards from Takeda, Servier, Roche, Genmab, Celgene, Regeneron and Incyte. S.F.B. is on the speaker's bureau of Takeda and Hofman la Roche and received departmental funding from Bristol Myers Squibb international corporation, Pfizer and Amgen Ltd. J.M.Z. received research funding from Roche and received honoraria for advisory boards from Takeda, Gilead and Roche. All remaining authors have declared no conflict of interest. This work was financially supported by an Alpe d'Huzes/KWF fund provided by the Dutch Cancer Society (# VU 2012–5848). The PETAL trial was supported by grants from the Deutsche Krebshilfe (no. 107592 and no. 110515). Greuter MJE: Conceptualization, Formal analysis, Writing - original draft; Eertink JJ: Conceptualization, Formal analysis; Jongeneel G: Formal analysis; Dührsen U: Data curation; Hüttmann A: Data curation; Schmitz C: Data curation; Lugtenburg PJ: Data curation; Barrington SF: Data curation; Mikhaeel NG: Data curation; Ceriani L: Data curation; Zucca E: Data curation; Carr R: Data curation; Györke T: Data curation; Burggraaff CN: Conceptualization, Formal analysis; de Vet HCW: Conceptualization; Hoekstra OS: Conceptualization; Zijlstra JM: Conceptualization; Coupé VMH: Conceptualization. Publisher Copyright: © 2021

PY - 2022/6/1

Y1 - 2022/6/1

N2 - Background: Guideline recommendations for diffuse large-B-cell lymphoma (DLBCL) treatment are shifting from long to short treatment duration, although it is still unclear whether shortening treatment duration does not cause any harm. As interim PET (I-PET) has high negative predictive value for progression, we evaluated the cost-effectiveness of shortening treatment duration dependent on I-PET result. Materials and Methods: We developed a Markov cohort model using the PET Re-Analysis (PETRA) database to evaluate a long treatment duration (LTD) strategy, ie 8x R-CHOP or 6x R-CHOP plus 2 R, and a short treatment duration (STD) strategy, ie 6x R-CHOP. Strategies were evaluated separately in I-PET2 positive and I-PET2 negative patients. Outcomes included total costs and quality-adjusted life-years (QALYs) per patient (pp) from a societal perspective. Net monetary benefit (NMB) per strategy was calculated using a willingness-to-pay threshold of €50,000/QALY. Robustness of model predictions was assessed in sensitivity analyses. Results: In I-PET2 positive patients, shortening treatment duration led to 50.4 additional deaths per 1000 patients. The STD strategy was less effective (-0.161 [95%CI: -0.343;0.028] QALYs pp) and less costly (-€2768 [95%CI: -€8420;€1105] pp). Shortening treatment duration was not cost-effective (incremental NMB -€5281). In I-PET2 negative patients, shortening treatment duration led to 5.0 additional deaths per 1000 patients and a minor difference in effectiveness (-0.007 [95%CI: -0.136;0.140] QALY pp). The STD strategy was less costly (-€5807 [95%CI: -€10,724;-€2685] pp) and led to an incremental NMB of €5449, indicating that it is cost-effective to shorten treatment duration. Robustness of these findings was underpinned by deterministic and probabilistic sensitivity analyses. Conclusion: Treatment duration should not be shortened in I-PET2 positive patients whereas it is cost-effective to shorten treatment duration in I-PET2 negative patients.

AB - Background: Guideline recommendations for diffuse large-B-cell lymphoma (DLBCL) treatment are shifting from long to short treatment duration, although it is still unclear whether shortening treatment duration does not cause any harm. As interim PET (I-PET) has high negative predictive value for progression, we evaluated the cost-effectiveness of shortening treatment duration dependent on I-PET result. Materials and Methods: We developed a Markov cohort model using the PET Re-Analysis (PETRA) database to evaluate a long treatment duration (LTD) strategy, ie 8x R-CHOP or 6x R-CHOP plus 2 R, and a short treatment duration (STD) strategy, ie 6x R-CHOP. Strategies were evaluated separately in I-PET2 positive and I-PET2 negative patients. Outcomes included total costs and quality-adjusted life-years (QALYs) per patient (pp) from a societal perspective. Net monetary benefit (NMB) per strategy was calculated using a willingness-to-pay threshold of €50,000/QALY. Robustness of model predictions was assessed in sensitivity analyses. Results: In I-PET2 positive patients, shortening treatment duration led to 50.4 additional deaths per 1000 patients. The STD strategy was less effective (-0.161 [95%CI: -0.343;0.028] QALYs pp) and less costly (-€2768 [95%CI: -€8420;€1105] pp). Shortening treatment duration was not cost-effective (incremental NMB -€5281). In I-PET2 negative patients, shortening treatment duration led to 5.0 additional deaths per 1000 patients and a minor difference in effectiveness (-0.007 [95%CI: -0.136;0.140] QALY pp). The STD strategy was less costly (-€5807 [95%CI: -€10,724;-€2685] pp) and led to an incremental NMB of €5449, indicating that it is cost-effective to shorten treatment duration. Robustness of these findings was underpinned by deterministic and probabilistic sensitivity analyses. Conclusion: Treatment duration should not be shortened in I-PET2 positive patients whereas it is cost-effective to shorten treatment duration in I-PET2 negative patients.

UR - https://www.scopus.com/pages/publications/85121591032

U2 - 10.1016/j.clml.2021.11.008

DO - 10.1016/j.clml.2021.11.008

M3 - Article

C2 - 34953740

AN - SCOPUS:85121591032

SN - 2152-2650

VL - 22

SP - 382

EP - 392

JO - Clinical Lymphoma, Myeloma and Leukemia

JF - Clinical Lymphoma, Myeloma and Leukemia

IS - 6

ER -

Cost-Effectiveness of Shortening Treatment Duration Based on Interim PET Outcome in Patients With Diffuse Large B-cell Lymphoma

Abstract

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