Skip to main content
Top
Published in: Advances in Therapy 7/2020

01-07-2020 | Chronic Lymphocytic Leukemia | Original Research

Real-World Treatment Patterns, Adverse Events, Resource Use, and Costs Among Commercially Insured, Younger Patients with Chronic Lymphocytic Leukemia in the USA: A Retrospective Cohort Study

Authors: Shaum M. Kabadi, Aimee Near, Keiko Wada, Chakkarin Burudpakdee

Published in: Advances in Therapy | Issue 7/2020

Login to get access

Abstract

Introduction

Amidst a changing treatment landscape, real-world evidence on the burden of chronic lymphocytic leukemia (CLL) is limited. The purpose of this study was to describe treatment patterns, adverse events (AEs), and economic burden among treated patients with CLL.

Methods

A retrospective cohort study was conducted with IQVIA PharMetrics® Plus. Patients at least 18 years old with CLL treatment between November 1, 2013 and May 31, 2018 were identified; index date was first observed CLL treatment. Patients had at least one CLL diagnosis pre-index and a second diagnosis anytime during the study period, at least 1-year pre- and at least 30-day post-index continuous enrollment and no pre-index CLL treatment. Analyses focused on patients receiving one of the four most common regimens observed. Outcomes included treatment patterns, frequency of incident AEs, and healthcare resource use and costs. Multivariable logistic regression and generalized linear modelling were used to evaluate risk of hospitalization and all-cause costs per patient per month (PPPM).

Results

A total of 1706 patients were included in the study (median [interquartile range] age 58 [55–62] years, 66% male, median Charlson Comorbidity Index 2 [2–3], median follow-up 16 [8–28] months). Common regimens, irrespective of treatment line, were bendamustine–rituximab (B-R, 27%), ibrutinib monotherapy (I, 27%), rituximab monotherapy (R, 19%), and fludarabine combined with cyclophosphamide and rituximab (FCR, 16%); 59% had at least one incident AE (B-R, 62%; I, 60%; R, 25%; FCR, 79%). Mean total all-cause healthcare cost over follow-up was $13,858 ± 14,626 PPPM. Increased number of AEs was associated with increased odds of hospitalization (odds ratio = 2.9; 95% confidence interval [CI] 2.5–3.4) and increased mean cost PPPM (cost ratio = 1.2; 95% CI 1.1–1.2).

Conclusion

This study highlights the treatment toxicity and associated economic burden among patients with CLL in the USA. As novel therapies are increasingly used, further research examining outcomes will inform the risks, benefits, and value of novel agents to prescribers and patients.
Appendix
Available only for authorised users
Literature
1.
go back to reference American Cancer Society. Cancer facts & figures 2019. Atlanta: American Cancer Society; 2019. American Cancer Society. Cancer facts & figures 2019. Atlanta: American Cancer Society; 2019.
2.
go back to reference Seymour EK, Ruterbusch JJ, Beebe-Dimmer JL, Schiffer CA. Real-world testing and treatment patterns in chronic lymphocytic leukemia: a SEER patterns of care analysis. Cancer. 2019;125(1):135–43.CrossRef Seymour EK, Ruterbusch JJ, Beebe-Dimmer JL, Schiffer CA. Real-world testing and treatment patterns in chronic lymphocytic leukemia: a SEER patterns of care analysis. Cancer. 2019;125(1):135–43.CrossRef
3.
go back to reference Brenner H, Gondos A, Pulte D. Trends in long-term survival of patients with chronic lymphocytic leukemia from the 1980s to the early 21st century. Blood. 1980s;111(10):4916–21.CrossRef Brenner H, Gondos A, Pulte D. Trends in long-term survival of patients with chronic lymphocytic leukemia from the 1980s to the early 21st century. Blood. 1980s;111(10):4916–21.CrossRef
5.
go back to reference Mato A, Jahnke J, Li P, et al. Real-world treatment and outcomes among older adults with chronic lymphocytic leukemia before the novel agents era. Haematologica. 2018;103:e0462. Mato A, Jahnke J, Li P, et al. Real-world treatment and outcomes among older adults with chronic lymphocytic leukemia before the novel agents era. Haematologica. 2018;103:e0462.
6.
go back to reference Wierda WG, Zelenetz AD, Gordon LI, et al. NCCN guidelines insights: chronic lymphocytic leukemia/small lymphocytic lymphoma, version 1.2017. J Natl Compr Canc Netw. 2017;15(3):293–311.CrossRef Wierda WG, Zelenetz AD, Gordon LI, et al. NCCN guidelines insights: chronic lymphocytic leukemia/small lymphocytic lymphoma, version 1.2017. J Natl Compr Canc Netw. 2017;15(3):293–311.CrossRef
7.
go back to reference Zelenetz AD, Gordon LI, Wierda WG, et al. Chronic lymphocytic leukemia/small lymphocytic lymphoma, version 1.2015. J Natl Compr Canc Netw. 2015;13(3):326–62.CrossRef Zelenetz AD, Gordon LI, Wierda WG, et al. Chronic lymphocytic leukemia/small lymphocytic lymphoma, version 1.2015. J Natl Compr Canc Netw. 2015;13(3):326–62.CrossRef
10.
go back to reference Mato AR, Nabhan C, Barr PM, et al. Outcomes of CLL patients treated with sequential kinase inhibitor therapy: a real world experience. Blood. 2016;128(18):2199–205.CrossRef Mato AR, Nabhan C, Barr PM, et al. Outcomes of CLL patients treated with sequential kinase inhibitor therapy: a real world experience. Blood. 2016;128(18):2199–205.CrossRef
11.
go back to reference Mato AR, Allan JN, Pagel JM, et al. Front-line ibrutinib therapy for chronic lymphocytic leukemia (CLL) in the real world: responses, toxicity, outcomes and subsequent therapies. Blood. 2017;130(Suppl 1):3011. Mato AR, Allan JN, Pagel JM, et al. Front-line ibrutinib therapy for chronic lymphocytic leukemia (CLL) in the real world: responses, toxicity, outcomes and subsequent therapies. Blood. 2017;130(Suppl 1):3011.
12.
go back to reference Byrd JC, Brown JR, O'Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213–23.CrossRef Byrd JC, Brown JR, O'Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213–23.CrossRef
13.
go back to reference Woyach JA, Ruppert AS, Heerema NA, et al. Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL. N Engl J Med. 2018;379(26):2517–28.CrossRef Woyach JA, Ruppert AS, Heerema NA, et al. Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL. N Engl J Med. 2018;379(26):2517–28.CrossRef
14.
go back to reference Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373(25):2425–37.CrossRef Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373(25):2425–37.CrossRef
15.
go back to reference Shanafelt TD, Wang V, Kay NE, et al. A randomized phase III study of ibrutinib (PCI-32765)-based therapy vs. standard fludarabine, cyclophosphamide, and rituximab (FCR) chemoimmunotherapy in untreated younger patients with chronic lymphocytic leukemia (CLL): a trial of the ECOG-ACRIN cancer research group (E1912). Blood. 2018;132(Suppl. 1):LBA-4.CrossRef Shanafelt TD, Wang V, Kay NE, et al. A randomized phase III study of ibrutinib (PCI-32765)-based therapy vs. standard fludarabine, cyclophosphamide, and rituximab (FCR) chemoimmunotherapy in untreated younger patients with chronic lymphocytic leukemia (CLL): a trial of the ECOG-ACRIN cancer research group (E1912). Blood. 2018;132(Suppl. 1):LBA-4.CrossRef
17.
go back to reference Byfield SD, Korrer S, Ellis L, Schenkel B. Real world treatment patterns and healthcare resource utilization (HRU) among chronic lymphocytic leukemia (CLL) patients by regimen. J Clin Oncol. 2015;34:15. Byfield SD, Korrer S, Ellis L, Schenkel B. Real world treatment patterns and healthcare resource utilization (HRU) among chronic lymphocytic leukemia (CLL) patients by regimen. J Clin Oncol. 2015;34:15.
18.
go back to reference Schenkel B, Ellis L, Korrer S, Byfield SD. Real-world treatment patterns and health care resource utilization (HRU) among patients with chronic lymphocytic leukemia (CLL) by regimen. J Clin Oncol. 2016;34(7_suppl):15.CrossRef Schenkel B, Ellis L, Korrer S, Byfield SD. Real-world treatment patterns and health care resource utilization (HRU) among patients with chronic lymphocytic leukemia (CLL) by regimen. J Clin Oncol. 2016;34(7_suppl):15.CrossRef
19.
go back to reference To TM, Yeh W-S, Biondo J, Masaquel AS. Patterns of ibrutinib use, discontinuation, and hospitalization among patients with chronic lymphocytic leukemia (CLL) in a US healthcare claims database. Blood. 2018;132(Suppl_1):5909.CrossRef To TM, Yeh W-S, Biondo J, Masaquel AS. Patterns of ibrutinib use, discontinuation, and hospitalization among patients with chronic lymphocytic leukemia (CLL) in a US healthcare claims database. Blood. 2018;132(Suppl_1):5909.CrossRef
20.
go back to reference Nordstrom BL, Knopf KB, Teltsch DY, Engle R, Beygi H, Sterchele JA. The safety of bendamustine in patients with chronic lymphocytic leukemia or non-Hodgkin lymphoma and concomitant renal impairment: a retrospective electronic medical record database analysis. Leuk Lymphoma. 2014;55(6):1266–73.CrossRef Nordstrom BL, Knopf KB, Teltsch DY, Engle R, Beygi H, Sterchele JA. The safety of bendamustine in patients with chronic lymphocytic leukemia or non-Hodgkin lymphoma and concomitant renal impairment: a retrospective electronic medical record database analysis. Leuk Lymphoma. 2014;55(6):1266–73.CrossRef
21.
go back to reference Kabadi S, Goyal RK, Nagar SP, Kaye JA, Davis KL, Mato AR. Treatment patterns, adverse events, and economic burden in a privately insured population of newly diagnosed patients with chronic lymphocytic leukemia in the United States. Blood. 2018;132(Suppl 1):3557.CrossRef Kabadi S, Goyal RK, Nagar SP, Kaye JA, Davis KL, Mato AR. Treatment patterns, adverse events, and economic burden in a privately insured population of newly diagnosed patients with chronic lymphocytic leukemia in the United States. Blood. 2018;132(Suppl 1):3557.CrossRef
22.
go back to reference Fowler NH. Role of maintenance rituximab (rituxan) therapy in the treatment of follicular lymphoma. Pharm Ther. 2011;36(9):590–8. Fowler NH. Role of maintenance rituximab (rituxan) therapy in the treatment of follicular lymphoma. Pharm Ther. 2011;36(9):590–8.
23.
go back to reference Inoue N, Nishimura N, Takahashi A, et al. Rituximab maintenance therapy is an effective therapy in over-sixties with mantle cell lymphoma. Am Soc Hematol. 2015;126(23):5081. Inoue N, Nishimura N, Takahashi A, et al. Rituximab maintenance therapy is an effective therapy in over-sixties with mantle cell lymphoma. Am Soc Hematol. 2015;126(23):5081.
24.
go back to reference Kenkre VP, Long WL, Eickhoff JC, et al. Maintenance rituximab following induction chemo-immunotherapy for mantle cell lymphoma: long-term follow-up of a pilot study from the Wisconsin Oncology Network. Leuk Lymphoma. 2011;52(9):1675–80.CrossRef Kenkre VP, Long WL, Eickhoff JC, et al. Maintenance rituximab following induction chemo-immunotherapy for mantle cell lymphoma: long-term follow-up of a pilot study from the Wisconsin Oncology Network. Leuk Lymphoma. 2011;52(9):1675–80.CrossRef
25.
go back to reference Romano PS, Roos LL, Jollis JG. Presentation adapting a clinical comorbidity index for use with ICD-9-CM administrative data: differing perspectives. J Clin Epidemiol. 1993;46:1075–9.CrossRef Romano PS, Roos LL, Jollis JG. Presentation adapting a clinical comorbidity index for use with ICD-9-CM administrative data: differing perspectives. J Clin Epidemiol. 1993;46:1075–9.CrossRef
26.
go back to reference Chyou JY, Hunter TD, Mollenkopf SA, Turakhia MP, Reynolds MR. Individual and combined risk factors for incident atrial fibrillation and incident stroke: an analysis of 3 million at-risk US patients. J Am Heart Assoc. 2015;4(7):e001723.CrossRef Chyou JY, Hunter TD, Mollenkopf SA, Turakhia MP, Reynolds MR. Individual and combined risk factors for incident atrial fibrillation and incident stroke: an analysis of 3 million at-risk US patients. J Am Heart Assoc. 2015;4(7):e001723.CrossRef
27.
go back to reference Chanan-Khan A, Cramer P, Demirkan F, et al. Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study. Lancet Oncol. 2016;17(2):200–11.CrossRef Chanan-Khan A, Cramer P, Demirkan F, et al. Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study. Lancet Oncol. 2016;17(2):200–11.CrossRef
28.
go back to reference Shanafelt TD, Wang V, Kay NE, et al. A randomized phase III study of ibrutinib (PCI-32765)-based therapy vs. standard fludarabine, cyclophosphamide, and rituximab (FCR) chemoimmunotherapy in untreated younger patients with chronic lymphocytic leukemia (CLL): a trial of the ECOG-ACRIN cancer research group (E1912). Blood. 2018;132(Suppl 1):LBA-4.CrossRef Shanafelt TD, Wang V, Kay NE, et al. A randomized phase III study of ibrutinib (PCI-32765)-based therapy vs. standard fludarabine, cyclophosphamide, and rituximab (FCR) chemoimmunotherapy in untreated younger patients with chronic lymphocytic leukemia (CLL): a trial of the ECOG-ACRIN cancer research group (E1912). Blood. 2018;132(Suppl 1):LBA-4.CrossRef
29.
go back to reference Tedeschi A, Greil R, Demirkan F, et al. Single-agent ibrutinib versus chlorambucil-obinutuzumab as first-line treatment in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL): results of a cross-trial comparison. Blood. 2018;132(Suppl 1):5565.CrossRef Tedeschi A, Greil R, Demirkan F, et al. Single-agent ibrutinib versus chlorambucil-obinutuzumab as first-line treatment in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL): results of a cross-trial comparison. Blood. 2018;132(Suppl 1):5565.CrossRef
30.
go back to reference Woyach JA, Ruppert AS, Heerema NA, et al. Ibrutinib alone or in combination with rituximab produces superior progression free survival (PFS) compared with bendamustine plus rituximab in untreated older patients with chronic lymphocytic leukemia (CLL): results of alliance North American intergroup study A041202. Blood. 2018;132(Suppl 1):6.CrossRef Woyach JA, Ruppert AS, Heerema NA, et al. Ibrutinib alone or in combination with rituximab produces superior progression free survival (PFS) compared with bendamustine plus rituximab in untreated older patients with chronic lymphocytic leukemia (CLL): results of alliance North American intergroup study A041202. Blood. 2018;132(Suppl 1):6.CrossRef
31.
go back to reference Mato AR, Barrientos JC, Brander DM, et al. Prognostic testing and treatment approaches in patients with chronic lymphocytic leukemia: clinical experience from an interim analysis of the inform CLL™ real-world registry. Blood. 2018;132(Suppl 1):4425.CrossRef Mato AR, Barrientos JC, Brander DM, et al. Prognostic testing and treatment approaches in patients with chronic lymphocytic leukemia: clinical experience from an interim analysis of the inform CLL™ real-world registry. Blood. 2018;132(Suppl 1):4425.CrossRef
32.
go back to reference Tang B, Szabo E, Zhou J, Wu J, Brander DM. Real-world characteristics of CLL patients receiving front-line therapy, using the Flatiron Health Database. Blood. 2017;130(Suppl 1):4671. Tang B, Szabo E, Zhou J, Wu J, Brander DM. Real-world characteristics of CLL patients receiving front-line therapy, using the Flatiron Health Database. Blood. 2017;130(Suppl 1):4671.
33.
go back to reference Kasi PM, Tawbi HA, Oddis CV, Kulkarni HS. Clinical review: serious adverse events associated with the use of rituximab-a critical care perspective. Crit Care. 2012;16(4):231.CrossRef Kasi PM, Tawbi HA, Oddis CV, Kulkarni HS. Clinical review: serious adverse events associated with the use of rituximab-a critical care perspective. Crit Care. 2012;16(4):231.CrossRef
34.
go back to reference Stephens DM, Byrd JC. How we manage ibrutinib intolerance and complications in patients with chronic lymphocytic leukemia. Blood. 2019;133(12):1298–301.CrossRef Stephens DM, Byrd JC. How we manage ibrutinib intolerance and complications in patients with chronic lymphocytic leukemia. Blood. 2019;133(12):1298–301.CrossRef
35.
go back to reference Matasar MJ, Dacosta Byfield S, Blauer-Peterson C, Montez M, Reyes C, Masaquel A. Real-world health care utilization and costs among patients newly initiating systemic therapy for chronic lymphocytic leukemia (CLL) in the United States. Blood. 2016;128(22):5928.CrossRef Matasar MJ, Dacosta Byfield S, Blauer-Peterson C, Montez M, Reyes C, Masaquel A. Real-world health care utilization and costs among patients newly initiating systemic therapy for chronic lymphocytic leukemia (CLL) in the United States. Blood. 2016;128(22):5928.CrossRef
36.
go back to reference Goyal RK, Nagar SP, Kabadi SM, Kaye JA, Seal B, Mato AR. Adverse events, resource use, and economic burden associated with mantle cell lymphoma: a real-world assessment of privately insured patients in the United States. Leuk Lymphoms. 2018;60:1–9. Goyal RK, Nagar SP, Kabadi SM, Kaye JA, Seal B, Mato AR. Adverse events, resource use, and economic burden associated with mantle cell lymphoma: a real-world assessment of privately insured patients in the United States. Leuk Lymphoms. 2018;60:1–9.
37.
go back to reference Chen Q, Jain N, Ayer T, et al. Economic burden of chronic lymphocytic leukemia in the era of oral targeted therapies in the United States. J Clin Oncol. 2017;35(2):166.CrossRef Chen Q, Jain N, Ayer T, et al. Economic burden of chronic lymphocytic leukemia in the era of oral targeted therapies in the United States. J Clin Oncol. 2017;35(2):166.CrossRef
38.
go back to reference Pfeil AM, Imfeld P, Pettengell R, et al. Trends in incidence and medical resource utilisation in patients with chronic lymphocytic leukaemia: insights from the UK Clinical Practice Research Datalink (CPRD). Ann Hematol. 2015;94(3):421–9.CrossRef Pfeil AM, Imfeld P, Pettengell R, et al. Trends in incidence and medical resource utilisation in patients with chronic lymphocytic leukaemia: insights from the UK Clinical Practice Research Datalink (CPRD). Ann Hematol. 2015;94(3):421–9.CrossRef
39.
go back to reference Wong W, Yim YM, Kim A, et al. Assessment of costs associated with adverse events in patients with cancer. PLoS One. 2018;13(4):e0196007.CrossRef Wong W, Yim YM, Kim A, et al. Assessment of costs associated with adverse events in patients with cancer. PLoS One. 2018;13(4):e0196007.CrossRef
Metadata
Title
Real-World Treatment Patterns, Adverse Events, Resource Use, and Costs Among Commercially Insured, Younger Patients with Chronic Lymphocytic Leukemia in the USA: A Retrospective Cohort Study
Authors
Shaum M. Kabadi
Aimee Near
Keiko Wada
Chakkarin Burudpakdee
Publication date
01-07-2020
Publisher
Springer Healthcare
Published in
Advances in Therapy / Issue 7/2020
Print ISSN: 0741-238X
Electronic ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-020-01350-w

Other articles of this Issue 7/2020

Advances in Therapy 7/2020 Go to the issue