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Current Hematologic Malignancy Reports

, Volume 13, Issue 4, pp 237–243 | Cite as

Economic Impact of Oral Therapies for Chronic Lymphocytic Leukemia—the Burden of Novelty

  • Talal Hilal
  • Jeffrey A. Betcher
  • Jose F. Leis
Health Economics (N Khera, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Health Economics

Abstract

Purpose of Review

Small molecule tyrosine kinase inhibitors (TKIs) and BCL2 inhibitors are oral targeted therapies that have changed the treatment approach to patients with chronic lymphocytic leukemia (CLL). The aim of this review is to summarize the relevant literature on the economic impact of oral novel therapies for the treatment of CLL and discuss the underlying factors and suggested solutions for high drug prices.

Recent Findings

The cost of therapy for CLL has increased substantially since the introduction of oral therapies. This increase in cost is caused by multiple factors including cost of drug development, alternate reimbursement patterns, lack of transparency, and lack of free market competition.

Summary

Oral therapies for CLL have dramatically increased costs for both patients and payers. Some solutions to overcome this include value-based pricing, transparency, and legal action that allow Medicare to negotiate drug prices with manufacturers.

Keywords

CLL Ibrutinib Idelalisib Venetoclax Drug costs Pharmacoeconomics, financial toxicity 

Notes

Compliance with Ethical Standards

Conflict of Interest

Talal Hilal, Jeffrey A. Betcher, and Jose F. Leis declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major Importance

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Dighiero G, Maloum K, Desablens B, Cazin B, Navarro M, Leblay R, et al. Chlorambucil in indolent chronic lymphocytic leukemia. French Cooperative Group on Chronic Lymphocytic Leukemia. N Engl J Med. 1998;338(21):1506–14.CrossRefPubMedGoogle Scholar
  3. 3.
    Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010;376(9747):1164–74.CrossRefPubMedGoogle Scholar
  4. 4.
    Fischer K, Cramer P, Busch R, Bottcher S, Bahlo J, Schubert J, et al. Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2012;30(26):3209–16.CrossRefPubMedGoogle Scholar
  5. 5.
    Tam CS, O'Brien S, Wierda W, Kantarjian H, Wen S, Do KA, et al. Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. Blood. 2008;112(4):975–80.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Thompson PA, Tam CS, O'Brien SM, Wierda WG, Stingo F, Plunkett W, et al. Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia. Blood. 2016;127(3):303–9.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Wiestner A. The role of B-cell receptor inhibitors in the treatment of patients with chronic lymphocytic leukemia. Haematologica. 2015;100(12):1495–507.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Food and Drug Administration. Drugs@FDA: FDA Approved Drug Products. Available from: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm.
  9. 9.
    Burger JA, Tedeschi A, Barr PM, Robak T, Owen C, Ghia P, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373(25):2425–37.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Byrd JC, Brown JR, O'Brien S, Barrientos JC, Kay NE, Reddy NM, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213–23.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370(11):997–1007.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Brown JR, Hillmen P, O'Brien S, Barrientos JC, Reddy N, Coutre S, et al. Updated efficacy including genetic and clinical subgroup analysis and overall safety in the phase 3 RESONATE trial of ibrutinib versus ofatumumab in previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma. Blood. 2014;124(21):3331.Google Scholar
  13. 13.
    Farooqui MZ, Valdez J, Martyr S, Aue G, Saba N, Niemann CU, et al. Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: a phase 2, single-arm trial. Lancet Oncol. 2015;16(2):169–76.CrossRefPubMedGoogle Scholar
  14. 14.
    Sharman JP, Coutre SE, Furman RR, Cheson BD, Pagel JM, Hillmen P, et al. Efficacy of idelalisib in CLL subpopulations harboring del(17p) and other adverse prognostic factors: results from a phase 3, randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2014;32(15_suppl):7011.Google Scholar
  15. 15.
    Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, et al. PI3Kdelta inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014;370(11):1008–18.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Stilgenbauer S, Eichhorst B, Schetelig J, Coutre S, Seymour JF, Munir T, et al. Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study. Lancet Oncol. 2016;17(6):768–78.CrossRefPubMedGoogle Scholar
  17. 17.
    Shanafelt TD, Gunderson H, Call TG. Commentary: chronic lymphocytic leukemia—the price of progress. Oncologist. 2010;15(6):601–2.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Shanafelt TD, Borah BJ, Finnes HD, Chaffee KG, Ding W, Leis JF, et al. Impact of ibrutinib and idelalisib on the pharmaceutical cost of treating chronic lymphocytic leukemia at the individual and societal levels. J Oncol Pract. 2015;11(3):252–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Medicare Medicare Plan Finder. Available from: https://www.medicare.gov/find-a-plan/questions/home.aspx.
  20. 20.
    Dusetzina SB. Drug pricing trends for orally administered anticancer medications reimbursed by commercial health plans, 2000–2014. JAMA Oncol. 2016;2(7):960–1.CrossRefPubMedGoogle Scholar
  21. 21.
    Betcher J, Dow E, Khera N. Oral chemotherapy in patients with hematological malignancies-care process, pharmacoeconomic and policy implications. Curr Hematol Malig Rep. 2016;11(4):288–94.CrossRefPubMedGoogle Scholar
  22. 22.
    Dusetzina SB, Huskamp HA, Winn AN, Basch E, Keating NL. Out-of-pocket and health care spending changes for patients using orally administered anticancer therapy after adoption of state parity Laws. JAMA Oncol. 2017;Google Scholar
  23. 23.
    Kircher SM, Meeker CR, Nimeiri H, Geynisman DM, Zafar SY, Shankaran V, et al. The parity paradigm: can legislation help reduce the cost burden of oral anticancer medications? Value Health. 2016;19(1):88–98.CrossRefPubMedGoogle Scholar
  24. 24.
    Henry J. Kaiser Family Foundation: The Medicare Part D Prescription. Drug Benefit 2017. Available from: https://www.kff.org/medicare/fact-sheet/the-medicare-prescription-drug-benefit-fact-sheet/.
  25. 25.
    Davidoff AJ, Erten M, Shaffer T, Shoemaker JS, Zuckerman IH, Pandya N, et al. Out-of-pocket health care expenditure burden for Medicare beneficiaries with cancer. Cancer. 2013;119(6):1257–65.CrossRefPubMedGoogle Scholar
  26. 26.
    • Chen Q, Jain N, Ayer T, Wierda WG, Flowers CR, O'Brien SM, 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):166–74. This study projects future cost burden of CLL with the use of oral targeted therapies. CrossRefPubMedGoogle Scholar
  27. 27.
    Jain N, Chen Q, Ayer T, O'Brien SM, Keating M, Wierda W, et al. Prevalence and economic burden of chronic lymphocytic leukemia (CLL) in the era of oral targeted therapies. Blood. 2015;126(23):871.Google Scholar
  28. 28.
    • Mailankody S, Prasad V. Five years of cancer drug approvals: innovation, efficacy, and costs. JAMA Oncol. 2015;1(4):539–40. This study highlights the disconnect between drug pricing and value to patients in terms of improved outcomes. CrossRefPubMedGoogle Scholar
  29. 29.
    DiMasi JA, Grabowski HG, Hansen RW. Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ. 2016;47:20–33.CrossRefPubMedGoogle Scholar
  30. 30.
    Prasad V, Mailankody S. Research and development spending to bring a single cancer drug to market and revenues after approval. JAMA Intern Med. 2017;177(11):1569–75.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    •• Kantarjian HM, Fojo T, Mathisen M, Zwelling LA. Cancer drugs in the United States: Justum Pretium—the just price. J Clin Oncol. 2013;31(28):3600–4. This article summarizes the issues contributing to high drug prices in the USA and proposes solutions. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Hillner BE, Smith TJ. Efficacy does not necessarily translate to cost effectiveness: a case study in the challenges associated with 21st-century cancer drug pricing. J Clin Oncol. 2009;27(13):2111–3.CrossRefPubMedGoogle Scholar
  33. 33.
    Mailankody S, Prasad V. Implications of proposed Medicare reforms to counteract high cancer drug prices. JAMA. 2016;316(3):271–2.CrossRefPubMedGoogle Scholar
  34. 34.
    Lyles A. Pharmacy benefit management companies: do they create value in the US healthcare system? PharmacoEconomics. 2017;35(5):493–500.CrossRefPubMedGoogle Scholar
  35. 35.
    Siddiqui M, Rajkumar SV. The high cost of cancer drugs and what we can do about it. Mayo Clin Proc. 2012;87(10):935–43.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Rajkumar SV, Harousseau JL. Next-generation multiple myeloma treatment: a pharmacoeconomic perspective. Blood. 2016;128(24):2757–64.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Prasad V, Mailankody S. The UK cancer drugs fund experiment and the US cancer drug cost problem: bearing the cost of cancer drugs until it is unbearable. Mayo Clin Proc. 2016;91(6):707–12.CrossRefPubMedGoogle Scholar
  38. 38.
    Bach PB. Limits on Medicare’s ability to control rising spending on cancer drugs. N Engl J Med. 2009;360(6):626–33.CrossRefPubMedGoogle Scholar
  39. 39.
    Lee TH, Emanuel EJ. Tier 4 drugs and the fraying of the social compact. N Engl J Med. 2008;359(4):333–5.CrossRefPubMedGoogle Scholar
  40. 40.
    NCCN Evidence Blocks. Available from: https://www.nccn.org/evidenceblocks/.
  41. 41.
    Tefferi A, Kantarjian H, Rajkumar SV, Baker LH, Abkowitz JL, Adamson JW, et al. In support of a patient-driven initiative and petition to lower the high price of cancer drugs. Mayo Clin Proc. 2015;90(8):996–1000.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    The Florida Senate: House Bill 351. Available from: https://www.flsenate.gov/Session/Bill/2018/00351.
  43. 43.
    Medicare Prescription Drug, Improvement, and Modernization Act of 2003. Available from: https://www.congress.gov/bill/108th-congress/house-bill/1.
  44. 44.
    Dreyling M, Jurczak W, Jerkeman M, Silva RS, Rusconi C, Trneny M, et al. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. Lancet. 2016;387(10020):770–8.CrossRefPubMedGoogle Scholar
  45. 45.
    Miklos D, Cutler CS, Arora M, Waller EK, Jagasia M, Pusic I, et al. Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood. 2017;130(21):2243–50.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Talal Hilal
    • 1
  • Jeffrey A. Betcher
    • 2
  • Jose F. Leis
    • 1
  1. 1.Division of Hematology and Medical OncologyMayo ClinicPhoenixUSA
  2. 2.Department of PharmacyMayo ClinicPhoenixUSA

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