Assessing the Effectiveness of Treatment Sequences for Older Patients With High-risk Follicular Lymphoma With a Multistate Model

Çağlar Çağlayan, Hiromi Terawaki, Turgay Ayer, Jordan S. Goldstein, Ashish Rai, Qiushi Chen, Christopher Flowers

Research output: Contribution to journalArticle

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Abstract

Background: Disease progression within < 2 years of initial chemoimmunotherapy and patient age > 60 years have been associated with poor overall survival (OS) in follicular lymphoma (FL). No standard treatment exists for these high-risk patients, and the effectiveness of sequential therapies remains unclear. Patients and Methods: We studied the course of FL with first-, second-, and third-line treatment. Using large population-based data, we identified 5234 patients with FL diagnosed in 2000 to 2009. Of these patients, 71% had received second-line therapy < 2 years, and 29% had received no therapy after first-line therapy, with a median OS of < 3 years. Treatment included rituximab, R-CVP (rituximab, cyclophosphamide, vincristine), R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine), R-Other (other rituximab-containing), and other regimens. The Aalen-Johansen estimator and Cox proportional hazards models were used to quantify the outcomes and assess the effects of the clinical and sociodemographic factors. Results: R-CHOP demonstrated the most favorable 5-year OS among first- (71%), second- (55%), and third-line (61%) therapies. First-line R-CHOP improved OS (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.50-0.64) and reduced the mortality risks after first-line (HR, 0.60; 95% CI, 0.47-0.77), second-line (HR, 0.40; 95% CI, 0.29-0.53), and third-line (HR, 0.63; 95% CI, 0.53-0.76) treatments. B-symptoms, being married, and histologic grade 1/2 were associated with the use of earlier second-line therapy. Early progression from second- to third-line therapy was associated with poor OS. The repeated use of R-CHOP or R-CVP as first- and second-line treatment yielded high 2-year mortality rates (R-CHOP + R-CHOP, 17.3%; R-CVP + R-CVP, 21.1%). Conclusion: Our multistate approach assessed the effect of sequential therapy on the immediate and subsequent treatment-line outcomes. We found that R-CHOP in any line improved OS for patients with high-risk FL.

Original languageEnglish (US)
Pages (from-to)300-309.e5
JournalClinical Lymphoma, Myeloma and Leukemia
Volume19
Issue number5
DOIs
StatePublished - May 1 2019

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Follicular Lymphoma
Survival
Therapeutics
Confidence Intervals
Vincristine
Cyclophosphamide
Mortality
Proportional Hazards Models
Disease Progression

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Çağlayan, Çağlar ; Terawaki, Hiromi ; Ayer, Turgay ; Goldstein, Jordan S. ; Rai, Ashish ; Chen, Qiushi ; Flowers, Christopher. / Assessing the Effectiveness of Treatment Sequences for Older Patients With High-risk Follicular Lymphoma With a Multistate Model. In: Clinical Lymphoma, Myeloma and Leukemia. 2019 ; Vol. 19, No. 5. pp. 300-309.e5.
@article{723c766917ad45c1919a7f63f09d15dd,
title = "Assessing the Effectiveness of Treatment Sequences for Older Patients With High-risk Follicular Lymphoma With a Multistate Model",
abstract = "Background: Disease progression within < 2 years of initial chemoimmunotherapy and patient age > 60 years have been associated with poor overall survival (OS) in follicular lymphoma (FL). No standard treatment exists for these high-risk patients, and the effectiveness of sequential therapies remains unclear. Patients and Methods: We studied the course of FL with first-, second-, and third-line treatment. Using large population-based data, we identified 5234 patients with FL diagnosed in 2000 to 2009. Of these patients, 71{\%} had received second-line therapy < 2 years, and 29{\%} had received no therapy after first-line therapy, with a median OS of < 3 years. Treatment included rituximab, R-CVP (rituximab, cyclophosphamide, vincristine), R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine), R-Other (other rituximab-containing), and other regimens. The Aalen-Johansen estimator and Cox proportional hazards models were used to quantify the outcomes and assess the effects of the clinical and sociodemographic factors. Results: R-CHOP demonstrated the most favorable 5-year OS among first- (71{\%}), second- (55{\%}), and third-line (61{\%}) therapies. First-line R-CHOP improved OS (hazard ratio [HR], 0.57; 95{\%} confidence interval [CI], 0.50-0.64) and reduced the mortality risks after first-line (HR, 0.60; 95{\%} CI, 0.47-0.77), second-line (HR, 0.40; 95{\%} CI, 0.29-0.53), and third-line (HR, 0.63; 95{\%} CI, 0.53-0.76) treatments. B-symptoms, being married, and histologic grade 1/2 were associated with the use of earlier second-line therapy. Early progression from second- to third-line therapy was associated with poor OS. The repeated use of R-CHOP or R-CVP as first- and second-line treatment yielded high 2-year mortality rates (R-CHOP + R-CHOP, 17.3{\%}; R-CVP + R-CVP, 21.1{\%}). Conclusion: Our multistate approach assessed the effect of sequential therapy on the immediate and subsequent treatment-line outcomes. We found that R-CHOP in any line improved OS for patients with high-risk FL.",
author = "{\cC}ağlar {\cC}ağlayan and Hiromi Terawaki and Turgay Ayer and Goldstein, {Jordan S.} and Ashish Rai and Qiushi Chen and Christopher Flowers",
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Assessing the Effectiveness of Treatment Sequences for Older Patients With High-risk Follicular Lymphoma With a Multistate Model. / Çağlayan, Çağlar; Terawaki, Hiromi; Ayer, Turgay; Goldstein, Jordan S.; Rai, Ashish; Chen, Qiushi; Flowers, Christopher.

In: Clinical Lymphoma, Myeloma and Leukemia, Vol. 19, No. 5, 01.05.2019, p. 300-309.e5.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Assessing the Effectiveness of Treatment Sequences for Older Patients With High-risk Follicular Lymphoma With a Multistate Model

AU - Çağlayan, Çağlar

AU - Terawaki, Hiromi

AU - Ayer, Turgay

AU - Goldstein, Jordan S.

AU - Rai, Ashish

AU - Chen, Qiushi

AU - Flowers, Christopher

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Background: Disease progression within < 2 years of initial chemoimmunotherapy and patient age > 60 years have been associated with poor overall survival (OS) in follicular lymphoma (FL). No standard treatment exists for these high-risk patients, and the effectiveness of sequential therapies remains unclear. Patients and Methods: We studied the course of FL with first-, second-, and third-line treatment. Using large population-based data, we identified 5234 patients with FL diagnosed in 2000 to 2009. Of these patients, 71% had received second-line therapy < 2 years, and 29% had received no therapy after first-line therapy, with a median OS of < 3 years. Treatment included rituximab, R-CVP (rituximab, cyclophosphamide, vincristine), R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine), R-Other (other rituximab-containing), and other regimens. The Aalen-Johansen estimator and Cox proportional hazards models were used to quantify the outcomes and assess the effects of the clinical and sociodemographic factors. Results: R-CHOP demonstrated the most favorable 5-year OS among first- (71%), second- (55%), and third-line (61%) therapies. First-line R-CHOP improved OS (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.50-0.64) and reduced the mortality risks after first-line (HR, 0.60; 95% CI, 0.47-0.77), second-line (HR, 0.40; 95% CI, 0.29-0.53), and third-line (HR, 0.63; 95% CI, 0.53-0.76) treatments. B-symptoms, being married, and histologic grade 1/2 were associated with the use of earlier second-line therapy. Early progression from second- to third-line therapy was associated with poor OS. The repeated use of R-CHOP or R-CVP as first- and second-line treatment yielded high 2-year mortality rates (R-CHOP + R-CHOP, 17.3%; R-CVP + R-CVP, 21.1%). Conclusion: Our multistate approach assessed the effect of sequential therapy on the immediate and subsequent treatment-line outcomes. We found that R-CHOP in any line improved OS for patients with high-risk FL.

AB - Background: Disease progression within < 2 years of initial chemoimmunotherapy and patient age > 60 years have been associated with poor overall survival (OS) in follicular lymphoma (FL). No standard treatment exists for these high-risk patients, and the effectiveness of sequential therapies remains unclear. Patients and Methods: We studied the course of FL with first-, second-, and third-line treatment. Using large population-based data, we identified 5234 patients with FL diagnosed in 2000 to 2009. Of these patients, 71% had received second-line therapy < 2 years, and 29% had received no therapy after first-line therapy, with a median OS of < 3 years. Treatment included rituximab, R-CVP (rituximab, cyclophosphamide, vincristine), R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine), R-Other (other rituximab-containing), and other regimens. The Aalen-Johansen estimator and Cox proportional hazards models were used to quantify the outcomes and assess the effects of the clinical and sociodemographic factors. Results: R-CHOP demonstrated the most favorable 5-year OS among first- (71%), second- (55%), and third-line (61%) therapies. First-line R-CHOP improved OS (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.50-0.64) and reduced the mortality risks after first-line (HR, 0.60; 95% CI, 0.47-0.77), second-line (HR, 0.40; 95% CI, 0.29-0.53), and third-line (HR, 0.63; 95% CI, 0.53-0.76) treatments. B-symptoms, being married, and histologic grade 1/2 were associated with the use of earlier second-line therapy. Early progression from second- to third-line therapy was associated with poor OS. The repeated use of R-CHOP or R-CVP as first- and second-line treatment yielded high 2-year mortality rates (R-CHOP + R-CHOP, 17.3%; R-CVP + R-CVP, 21.1%). Conclusion: Our multistate approach assessed the effect of sequential therapy on the immediate and subsequent treatment-line outcomes. We found that R-CHOP in any line improved OS for patients with high-risk FL.

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