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Impact of dose modification on intravenous Bortezomib-induced peripheral neuropathy in multiple myeloma patients

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Abstract

Purpose

Patients discontinue bortezomib treatment despite good response to the therapy because of bortezomib-induced neuropathy. Early and active dose reduction is recommended for efficacy of treatment. This study evaluates patterns of bortezomib-associated neuropathy and examines the effectiveness of dose modification on symptom management and treatment compliance.

Methods

This is a retrospective cohort study of multiple myeloma patients who received bortezomib intravenously from 2009 to 2012 at Samsung Medical Center, Seoul, Korea. Peripheral neuropathy was assessed using neurotoxicity subscale of the FACT/GOG-Ntx at daily clinical practice; physicians modified the dosage and schedule of bortezomib treatment. Mixed-effect models were used for evaluating changes of neuropathy symptoms over time. Linear spline models and multivariate logistic regression were used for testing the effectiveness of interventions.

Results

There were 1,060 visits of 55 multiple myeloma patients during the study period. Patients were most likely to have numbness of feet, painful burning in feet, muscle weakness, and the symptoms worsened over time (P < 0.05). For patients who received intervention (n = 32, 58.1 %), neuropathy symptoms were significantly decreased after the intervention (coefficient, −0.1 (95 % confidence interval (CI), −0.8, 0.6)). The intervention group had on average 5.19 (95 % CI, 3.79, 6.59) more bortezomib administrations and was 1.4 times more likely to complete the treatment (odds ratio, 1.40 (95 % CI, 0.31, 6.32)) than the nonintervention group.

Conclusion

Close monitoring of peripheral neuropathy in patients receiving bortezomib is a feasible and useful way to manage neuropathy in the real world.

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References

  1. Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, Rajkumar SV, Srkalovic G, Alsina M, Alexanian R, Siegel D, Orlowski RZ, Kuter D, Limentani SA, Lee S, Hideshima T, Esseltine DL, Kauffman M, Adams J, Schenkein DP, Anderson KC (2003) A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 348:2609–2617

    Article  CAS  PubMed  Google Scholar 

  2. San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS, Dmoszynska A, Abdulkadyrov KM, Schots R, Jiang B, Mateos MV, Anderson KC, Esseltine DL, Liu K, Cakana A, van de Velde H, Richardson PG, Investigators VT (2008) Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 359:906–917

    Article  CAS  PubMed  Google Scholar 

  3. Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, San-Miguel JF, Blade J, Boccadoro M, Cavenagh J, Dalton WS, Boral AL, Esseltine DL, Porter JB, Schenkein D, Anderson KC (2005) Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 352:2487–2498

    Article  CAS  PubMed  Google Scholar 

  4. Richardson PG, Briemberg H, Jagannath S, Wen PY, Barlogie B, Berenson J, Singhal S, Siegel DS, Irwin D, Schuster M, Srkalovic G, Alexanian R, Rajkumar SV, Limentani S, Alsina M, Orlowski RZ, Najarian K, Esseltine D, Anderson KC, Amato AA (2006) Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib. J Clin Oncol 24:3113–3120

    Article  CAS  PubMed  Google Scholar 

  5. Min CK, Lee MJ, Eom KS, Lee S, Lee JW, Min WS, Kim CC, Kim M, Lim J, Kim Y, Han K (2007) Bortezomib in combination with conventional chemotherapeutic agents for multiple myeloma compared with bortezomib alone. Jpn J Clin Oncol 37:961–968

    Article  PubMed  Google Scholar 

  6. Cavaletti G, Gilardini A, Canta A, Rigamonti L, Rodriguez-Menendez V, Ceresa C, Marmiroli P, Bossi M, Oggioni N, D'Incalci M, De Coster R (2007) Bortezomib-induced peripheral neurotoxicity: a neurophysiological and pathological study in the rat. Exp Neurol 204:317–325

    Article  CAS  PubMed  Google Scholar 

  7. Meregalli C, Chiorazzi A, Carozzi VA, Canta A, Sala B, Colombo M, Oggioni N, Ceresa C, Foudah D, La Russa F, Miloso M, Nicolini G, Marmiroli P, Bennett DL, Cavaletti G (2014) Evaluation of tubulin polymerization and chronic inhibition of proteasome as citotoxicity mechanisms in bortezomib-induced peripheral neuropathy. Cell Cycle 13:612–621

    Article  CAS  PubMed  Google Scholar 

  8. Azoulay D, Lavie D, Horowitz N, Suriu C, Gatt ME, Akria L, Perlman R, Braester A, Ben-Yehuda D (2014) Bortezomib-induced peripheral neuropathy is related to altered levels of brain-derived neurotrophic factor in the peripheral blood of patients with multiple myeloma. Br J Haematol 164:454–456

    Article  CAS  PubMed  Google Scholar 

  9. Becker PS (2011) Genetic predisposition for chemotherapy-induced neuropathy in multiple myeloma. J Clin Oncol 29:783–786

    Article  CAS  PubMed  Google Scholar 

  10. Broyl A, Corthals SL, Jongen JL, van der Holt B, Kuiper R, de Knegt Y, van Duin M, el Jarari L, Bertsch U, Lokhorst HM, Durie BG, Goldschmidt H, Sonneveld P (2010) Mechanisms of peripheral neuropathy associated with bortezomib and vincristine in patients with newly diagnosed multiple myeloma: a prospective analysis of data from the HOVON-65/GMMG-HD4 trial. Lancet Oncol 11:1057–1065

    Article  CAS  PubMed  Google Scholar 

  11. Badros A, Goloubeva O, Dalal JS, Can I, Thompson J, Rapoport AP, Heyman M, Akpek G, Fenton RG (2007) Neurotoxicity of bortezomib therapy in multiple myeloma: a single-center experience and review of the literature. Cancer 110:1042–1049

    Article  CAS  PubMed  Google Scholar 

  12. Richardson PG, Sonneveld P, Schuster MW, Stadtmauer EA, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, Blade J, Boccadoro M, Cavenagh JD, Boral AL, Esseltine DL, Wen PY, Amato AA, Anderson KC, San Miguel J (2009) Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase III APEX trial in relapsed multiple myeloma: impact of a dose-modification guideline. Br J Haematol 144:895–903

    Article  CAS  PubMed  Google Scholar 

  13. Dworkin RH, O'Connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, Kalso EA, Loeser JD, Miaskowski C, Nurmikko TJ, Portenoy RK, Rice AS, Stacey BR, Treede RD, Turk DC, Wallace MS (2007) Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain 132:237–251

    Article  CAS  PubMed  Google Scholar 

  14. Sonneveld P, Jongen JL (2010) Dealing with neuropathy in plasma-cell dyscrasias. Hematology Am Soc Hematol Educ Program 2010:423–430

    Article  PubMed  Google Scholar 

  15. FACIT.org. (2010) http://www.facit.org/FACITOrg/Questionnaires

  16. Calhoun EA, Welshman EE, Chang CH, Lurain JR, Fishman DA, Hunt TL, Cella D (2003) Psychometric evaluation of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx) questionnaire for patients receiving systemic chemotherapy. Int J Gynecol Cancer 13:741–748

    Article  CAS  PubMed  Google Scholar 

  17. Talamo G, Farooq U, Zangari M, Liao J, Dolloff NG, Loughran TP Jr, Epner E (2010) Beyond the CRAB symptoms: a study of presenting clinical manifestations of multiple myeloma. Clin Lymphoma Myeloma Leuk 10:464–468

    Article  PubMed  Google Scholar 

  18. Dimopoulos MA, Mateos MV, Richardson PG, Schlag R, Khuageva NK, Shpilberg O, Kropff M, Spicka I, Palumbo A, Wu KL, Esseltine DL, Liu K, Deraedt W, Cakana A, Van De Velde H, San Miguel JF (2011) Risk factors for, and reversibility of, peripheral neuropathy associated with bortezomib–melphalan–prednisone in newly diagnosed patients with multiple myeloma: subanalysis of the phase 3 VISTA study. Eur J Haematol 86:23–31

    Article  CAS  PubMed  Google Scholar 

  19. Lanzani F, Mattavelli L, Frigeni B, Rossini F, Cammarota S, Petro D, Jann S, Cavaletti G (2008) Role of a pre-existing neuropathy on the course of bortezomib-induced peripheral neurotoxicity. J Peripher Nerv Syst 13:267–274

    Article  PubMed  Google Scholar 

  20. Chaudhry V, Cornblath DR, Polydefkis M, Ferguson A, Borrello I (2008) Characteristics of bortezomib- and thalidomide-induced peripheral neuropathy. J Peripher Nerv Syst 13:275–282

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Corso A, Mangiacavalli S, Varettoni M, Pascutto C, Zappasodi P, Lazzarino M (2010) Bortezomib-induced peripheral neuropathy in multiple myeloma: a comparison between previously treated and untreated patients. Leuk Res 34:471–474

    Article  CAS  PubMed  Google Scholar 

  22. Richardson PG, Delforge M, Beksac M, Wen P, Jongen JL, Sezer O, Terpos E, Munshi N, Palumbo A, Rajkumar SV, Harousseau JL, Moreau P, Avet-Loiseau H, Lee JH, Cavo M, Merlini G, Voorhees P, Chng WJ, Mazumder A, Usmani S, Einsele H, Comenzo R, Orlowski R, Vesole D, Lahuerta JJ, Niesvizky R, Siegel D, Mateos MV, Dimopoulos M, Lonial S, Jagannath S, Blade J, Miguel JS, Morgan G, Anderson KC, Durie BG, Sonneveld P (2012) Management of treatment-emergent peripheral neuropathy in multiple myeloma. Leukemia 26:595–608

    Article  CAS  PubMed  Google Scholar 

  23. Arnulf B, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, van de Velde H, Feng H, Cakana A, Deraedt W, Moreau P (2012) Updated survival analysis of a randomized phase III study of subcutaneous versus intravenous bortezomib in patients with relapsed multiple myeloma. Haematologica 97:1925–1928

    Article  PubMed Central  PubMed  Google Scholar 

  24. Mateos MV, San Miguel JF (2012) Safety and efficacy of subcutaneous formulation of bortezomib versus the conventional intravenous formulation in multiple myeloma. Ther Adv Hematol 3:117–124

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

The authors thank Ms. Yun Jeong Kim and Mr. Seung Ho Jung (Janssen Korea) for insightful comments on the study.

Disclosure

All authors have no disclosure.

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Authors and Affiliations

  1. Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea

    Juhee Cho & Danbee Kang

  2. Cancer Education Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Juhee Cho

  3. Department of Health, Behavior and Society, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Juhee Cho

  4. Division of Hematology-Oncology, Department of Medicine, G SAM Hospital, Gunpo, South Korea

    Ji Yean Lee

  5. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, South Korea

    Kihyun Kim & Seok Jin Kim

  6. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Juhee Cho

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  1. Juhee Cho
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Correspondence to Seok Jin Kim.

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Cho, J., Kang, D., Lee, J.Y. et al. Impact of dose modification on intravenous Bortezomib-induced peripheral neuropathy in multiple myeloma patients. Support Care Cancer 22, 2669–2675 (2014). https://doi.org/10.1007/s00520-014-2256-6

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  • DOI: https://doi.org/10.1007/s00520-014-2256-6

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