A comparative analysis of prognostic factor models for follicular lymphoma based on a phase III trial of CHOP-rituximab versus CHOP + 131iodine- tositumomab

Oliver W. Press, Joseph M. Unger, Lisa M Rimsza, Jonathan W. Friedberg, Michael Leblanc, Myron S. Czuczman, Mark Kaminski, Rita M. Braziel, Catherine S Perry, Ajay K. Gopal, David G. Maloney, Bruce D. Cheson, Shaker R. Dakhil, Thomas P Miller, Richard I. Fisher

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Abstract

Purpose: There is currently no consensus on optimal frontline therapy for patients with follicular lymphoma. We analyzed a phase III randomized intergroup trial comparing six cycles of CHOP-R (cyclophosphamide-Adriamycin-vincristine- prednisone (Oncovin)-rituximab) with six cycles of CHOP followed by iodine-131 tositumomab radioimmunotherapy (RIT) to assess whether any subsets benefited more from one treatment or the other, and to compare three prognostic models. Experimental Design:Weconducted univariate and multivariate Cox regression analysesof532 patients enrolled on this trial and compared the prognostic value of the FLIPI (follicular lymphoma international prognostic index), FLIPI2, and LDH + β2M (lactate dehydrogenase + β2-microglobulin) models. Results: Outcomes were excellent, but not statistically different between the two study arms [5-year progression-free survival (PFS) of 60% with CHOP-R and 66% with CHOP-RIT (P = 0.11); 5-year overall survival (OS) of 92% with CHOP-R and 86% with CHOP-RIT (P = 0.08); overall response rate of 84% for both arms]. The only factor found to potentially predict the impact of treatment was serum β2M; among patients with normal β2M, CHOP-RIT patients had better PFS compared with CHOP-R patients, whereas among patients with high serum β2M, PFS by arm was similar (interaction P value = 0.02). Conclusions: All three prognostic models (FLIPI, FLIPI2, and LDH + β2M) predicted both PFS and OS well, though the LDH + β2M model is easiest to apply and identified an especially poor risk subset. In an exploratory analysis using the latter model, there was a statistically significant trend suggesting that low-risk patients had superior observed PFS if treated with CHOP-RIT, whereas high-risk patients had a better PFS with CHOP-R.

Original languageEnglish (US)
Pages (from-to)6624-6632
Number of pages9
JournalClinical Cancer Research
Volume19
Issue number23
DOIs
StatePublished - Dec 1 2013

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Follicular Lymphoma
Radioimmunotherapy
Disease-Free Survival
Vincristine
Survival
Rituximab
Prednisone
Serum
Doxorubicin
Cyclophosphamide
lactate dehydrogenase 2
Research Design
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A comparative analysis of prognostic factor models for follicular lymphoma based on a phase III trial of CHOP-rituximab versus CHOP + 131iodine- tositumomab. / Press, Oliver W.; Unger, Joseph M.; Rimsza, Lisa M; Friedberg, Jonathan W.; Leblanc, Michael; Czuczman, Myron S.; Kaminski, Mark; Braziel, Rita M.; Perry, Catherine S; Gopal, Ajay K.; Maloney, David G.; Cheson, Bruce D.; Dakhil, Shaker R.; Miller, Thomas P; Fisher, Richard I.

In: Clinical Cancer Research, Vol. 19, No. 23, 01.12.2013, p. 6624-6632.

Research output: Contribution to journalArticle

Press, OW, Unger, JM, Rimsza, LM, Friedberg, JW, Leblanc, M, Czuczman, MS, Kaminski, M, Braziel, RM, Perry, CS, Gopal, AK, Maloney, DG, Cheson, BD, Dakhil, SR, Miller, TP & Fisher, RI 2013, 'A comparative analysis of prognostic factor models for follicular lymphoma based on a phase III trial of CHOP-rituximab versus CHOP + 131iodine- tositumomab', Clinical Cancer Research, vol. 19, no. 23, pp. 6624-6632. https://doi.org/10.1158/1078-0432.CCR-13-1120
Press, Oliver W. ; Unger, Joseph M. ; Rimsza, Lisa M ; Friedberg, Jonathan W. ; Leblanc, Michael ; Czuczman, Myron S. ; Kaminski, Mark ; Braziel, Rita M. ; Perry, Catherine S ; Gopal, Ajay K. ; Maloney, David G. ; Cheson, Bruce D. ; Dakhil, Shaker R. ; Miller, Thomas P ; Fisher, Richard I. / A comparative analysis of prognostic factor models for follicular lymphoma based on a phase III trial of CHOP-rituximab versus CHOP + 131iodine- tositumomab. In: Clinical Cancer Research. 2013 ; Vol. 19, No. 23. pp. 6624-6632.
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abstract = "Purpose: There is currently no consensus on optimal frontline therapy for patients with follicular lymphoma. We analyzed a phase III randomized intergroup trial comparing six cycles of CHOP-R (cyclophosphamide-Adriamycin-vincristine- prednisone (Oncovin)-rituximab) with six cycles of CHOP followed by iodine-131 tositumomab radioimmunotherapy (RIT) to assess whether any subsets benefited more from one treatment or the other, and to compare three prognostic models. Experimental Design:Weconducted univariate and multivariate Cox regression analysesof532 patients enrolled on this trial and compared the prognostic value of the FLIPI (follicular lymphoma international prognostic index), FLIPI2, and LDH + β2M (lactate dehydrogenase + β2-microglobulin) models. Results: Outcomes were excellent, but not statistically different between the two study arms [5-year progression-free survival (PFS) of 60{\%} with CHOP-R and 66{\%} with CHOP-RIT (P = 0.11); 5-year overall survival (OS) of 92{\%} with CHOP-R and 86{\%} with CHOP-RIT (P = 0.08); overall response rate of 84{\%} for both arms]. The only factor found to potentially predict the impact of treatment was serum β2M; among patients with normal β2M, CHOP-RIT patients had better PFS compared with CHOP-R patients, whereas among patients with high serum β2M, PFS by arm was similar (interaction P value = 0.02). Conclusions: All three prognostic models (FLIPI, FLIPI2, and LDH + β2M) predicted both PFS and OS well, though the LDH + β2M model is easiest to apply and identified an especially poor risk subset. In an exploratory analysis using the latter model, there was a statistically significant trend suggesting that low-risk patients had superior observed PFS if treated with CHOP-RIT, whereas high-risk patients had a better PFS with CHOP-R.",
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T1 - A comparative analysis of prognostic factor models for follicular lymphoma based on a phase III trial of CHOP-rituximab versus CHOP + 131iodine- tositumomab

AU - Press, Oliver W.

AU - Unger, Joseph M.

AU - Rimsza, Lisa M

AU - Friedberg, Jonathan W.

AU - Leblanc, Michael

AU - Czuczman, Myron S.

AU - Kaminski, Mark

AU - Braziel, Rita M.

AU - Perry, Catherine S

AU - Gopal, Ajay K.

AU - Maloney, David G.

AU - Cheson, Bruce D.

AU - Dakhil, Shaker R.

AU - Miller, Thomas P

AU - Fisher, Richard I.

PY - 2013/12/1

Y1 - 2013/12/1

N2 - Purpose: There is currently no consensus on optimal frontline therapy for patients with follicular lymphoma. We analyzed a phase III randomized intergroup trial comparing six cycles of CHOP-R (cyclophosphamide-Adriamycin-vincristine- prednisone (Oncovin)-rituximab) with six cycles of CHOP followed by iodine-131 tositumomab radioimmunotherapy (RIT) to assess whether any subsets benefited more from one treatment or the other, and to compare three prognostic models. Experimental Design:Weconducted univariate and multivariate Cox regression analysesof532 patients enrolled on this trial and compared the prognostic value of the FLIPI (follicular lymphoma international prognostic index), FLIPI2, and LDH + β2M (lactate dehydrogenase + β2-microglobulin) models. Results: Outcomes were excellent, but not statistically different between the two study arms [5-year progression-free survival (PFS) of 60% with CHOP-R and 66% with CHOP-RIT (P = 0.11); 5-year overall survival (OS) of 92% with CHOP-R and 86% with CHOP-RIT (P = 0.08); overall response rate of 84% for both arms]. The only factor found to potentially predict the impact of treatment was serum β2M; among patients with normal β2M, CHOP-RIT patients had better PFS compared with CHOP-R patients, whereas among patients with high serum β2M, PFS by arm was similar (interaction P value = 0.02). Conclusions: All three prognostic models (FLIPI, FLIPI2, and LDH + β2M) predicted both PFS and OS well, though the LDH + β2M model is easiest to apply and identified an especially poor risk subset. In an exploratory analysis using the latter model, there was a statistically significant trend suggesting that low-risk patients had superior observed PFS if treated with CHOP-RIT, whereas high-risk patients had a better PFS with CHOP-R.

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