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The infection rate in new diagnosis and relapsed/refractory multiple myeloma patients who had bortezomib-based chemotherapy and relationship between development of infection and lymphocyte/monocyte ratio

Year 2021, Volume: 7 Issue: 6, 541 - 549, 04.11.2021
https://doi.org/10.18621/eurj.855510

Abstract

Objectives: Multiple Myeloma (MM) is a disease caused by the clonal proliferation of plasma cells. In recent years, proteozom inhibitors, immunomodulatory agents and monoclonal antibodies have been used in the treatment of MM. In this study, the relation of bortezomib, one of the proteozoma inhibitors used in the treatment of MM, with the development of infection was investigated.


Methods:
We retrospectively evaluated 56 patients who had MM treated with bortezomib-based regimen. We tried to determine the relationship between infection with immunoglobulin G levels at the time of diagnosis, lymphocyte absolute values at the time of diagnosis, lymphocyte absolute values at the time of chemotherapy, neutrophil absolute value at the time of chemotherapy, lymphocyte absolute values at the time of infection, monocyte absolute value at the time of infection, and the lymphocyte/monocyte (L/M) ratio at the time of infection. The effects of L/M ratio on progression free survival (PFS) and overall survival (OS) were also examined.


Results:
Thirty (53.6%) of the 56 patients were newly diagnosed, 26 (46.4%) of 56 patients were relapsed/refractory MM. The bortezomib-based regimen was given to all patients. Of the 56 patients included in the study, 21 (37.5%) were female, 35 were male (62.5%). The ages of the patients was 28-79 years (median: 58.5 years). No infection attack was observed in 31 (55.4%) patients. Disease stage (R-ISS) (p = 0.032), presence or absence of co-morbid disease (p = 0.035), disease status during an infection attack (p < 0.01), lymphocytopenia at the time of chemotherapy (p = 0.003), absolute value of lymphocytopenia at the time of infection attack (p < 0.01) and L/M ratio (p < 0.01) had a significant relation with development of infection. Lymphocytopenia at the time of infection attack (p < 0.01, OR<1, 94.6% CI) and L/M ratio (p < 0.01, OR<1, 91.1% CI) had been found significant in univariate logistic regression analysis. Lymphocytopenia at the time of infection attack (p = 0.002, OR<1, 95% CI) and L/M ratio (p = 0.003, OR<1, 95% CI) had been found significant in multivariate logistic regression analysis. L/M ratio had a significant effect on OS (p < 0.017) but not on PFS (p > 0.05).


Conclusions:
It was determined that L/M ratio has an effect on OS and it is also an independent factor on the development of infection. OS was decreasing and the risk of developing infection was increasing, when the L/M ratio was low.

References

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  • 2. Bergsagel DE, Sprague CC, Austin C, Griffith KM. Evaluation of new chemotherapeutic agents in the treatment of multiple myeloma: IV. L-Phenylalanine mustard (NSC-8806). Cancer Chemother Rep 1962;21:87-99.
  • 3. Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. N Engl J Med 1996;335:91-7.
  • 4. Morgan GJ1, Davies FE. Role of thalidomide in the treatment of patients with multiple myeloma. Crit Rev Oncol Hematol 2013;88 Suppl 1:S14-22.
  • 5. Abe Y , Ishida T. Immunomodulatory drugs in the treatment of multiple myeloma. Jpn J Clin Oncol 2019;49:695-702.
  • 6. Touzeau C, Moreau P. Daratumumab for the treatment of multiple myeloma. Expert Opin Biol Ther 2017;17:887-93.
  • 7. Pamukçuoğlu M, Emmez H, Tunçcan OG, Oner AY, Cırak MY, Senol E, et al. Brain abscess caused by Nocardia cyriacigeorgica in two patients with multiple myeloma: novel agents, new spectrum of infections. Hematology 2014;19:158-62.
  • 8. Kim SJ, Kim K, Kim BS, Lee HJ, Kim H, Lee NR, et al. Bortezomib and the increased incidence of herpes zoster in patients with multiple myeloma. Clin Lymphoma Myeloma 2008;8:237-40.
  • 9. Basler M, Lauer C, Beck U, Groettrup M. The proteasome inhibitor bortezomib enhances the susceptibility to viral infection. J Immunol 2009;183:6145-50.
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  • 11. Wu KL, van Wieringen W, Vellenga E, Zweegman S, Lokhorst HM, Sonneveld P. Analysis of the efficacy and toxicity of bortezomib for treatment of relapsed or refractory multiple myeloma in community practice. Haematologica 2005;90:996-7.
  • 12. Greipp PR, Miguel JS, Durie BGM, Crowley JJ, Barlogie B, Blad J, et al. International staging system for multiple myeloma. J Clin Oncol 2005;23:3412-20.
  • 13. Palumbo A, Loiseau HA, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, et al. Revised International Staging System for Multiple Myeloma: a report From International Myeloma Working Group. J Clin Oncol 2015;33:2863-9.
  • 14. Kropff M, Bisping G, Schuck E, Liebisch P, Lang N, Hentrich M, et al. Bortezomib in combination with intermediate-dose dexamethasone and continuous low-dose oral cyclophosphamide for relapsed multiple myeloma. Br J Haematol 2007;138:330-7.
  • 15. Pang Y, Shao H, Yang Z, Fan L, Liu W, Shi J, et al. The neutrophils+monocyte/lymphocyte ratio is an independent prognostic factor for progression-free survival in newly diagnosed multiple myeloma patients treated with BCD regimen. Front Oncol 2020;10:1617.
  • 16. Zeng Q, Liu Z, Li Q, Liu T. Prognostic value of neutrophil to lymphocyte ratio and clinicopathological characteristics for multiple myeloma. Medicine (Baltimore). 2018;97:e12678.
  • 17. Suriu C, Akria L, Azoulay D, Shaoul E, Barhoum M, Braester A. Absolute lymphocyte count as prognostic marker in newly diagnosed multiple myeloma patients. Int J Lab Hematol 2016;38:e56-9.
  • 18. Romano A, Parrinello NL, Consoli ML, Marchionni L, Forte S, Conticello C, et al. Neutrophil to lymphocyte ratio (NLR) improves the risk assessment of ISS staging in newly diagnosed MM patients treated upfront with novel agents. Ann Hematol 2015;94:1875-83.
  • 19. Wang J, Sun C, Xia J, Zhou X, Guo HF. Limited prognostic value of pretreatment neutrophil-to-lymphocyte ratios in elderly patients with multiple myeloma. Clin Lab 2018;64:507-13.
  • 20. Romano A, Laura PN, Cerchione C, Letizia CM, Parisi M, Calafiore V, et al. The NLR and LMR ratio in newly diagnosed MM patients treated upfront with novel agents. Blood Cancer J 2017;7:649.
  • 21. Raje N, Berdeja J, Lin Y, Siegel D, Jagannath S, Madduri D, et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N Engl J Med 2019;380:1726-37.
  • 22. Binder M, Rajkumar SV, Lacy MQ, Gertz MA, Buadi FK, Dispenzieri A, et al. Peripheral blood biomarkers of early immune reconstitution in newly diagnosed multiple myeloma. Am J Hematol 2019; 94:306-11.
  • 23. Ueda T, Chikuie N, Takumida M, Furuie H, Kono T, Taruya T, et al. Baseline neutrophil-to-lymphocyte ratio (NLR) is associated with clinical outcome in recurrent or metastatic head and neck cancer patients treated with nivolumab. Acta Otolaryngol 2020;140:181-7.
  • 24. Kosuga T, Konishi T, Kubota T, Shoda K, Konishi H, Shiozaki A, et al. Clinical significance of neutrophil-to-lymphocyte ratio as a predictor of lymph node metastasis in gastric cancer. BMC Cancer 2019;19:1187.
  • 25. Bento L, Díaz-López A, Barranco G, Martín-Moreno AM, Baile M, Martín A, et al. New prognosis score including absolute lymphocyte/monocyte ratio, red blood cell distribution width and beta-2 microglobulin in patients with diffuse large B-cell lymphoma treated with R-CHOP: Spanish Lymphoma Group Experience (GELTAMO). Br J Haematol 2020;188:888-97.
  • 26. Dosani T, Covut F, Beck R, Driscoll JJ, de Lima M, Malek E. Significance of the absolute lymphocyte/monocyte ratio as a prognostic immune biomarker in newly diagnosed multiple myeloma. Blood Cancer J 2017;7:e579.
  • 27. Yang Y, Liu Z, Wang H. Peripheral absolute lymphocyte count: an economical and clinical available immune-related prognostic marker for newly diagnosed multiple myeloma. Med Sci Monit 2020;26:e923716.
Year 2021, Volume: 7 Issue: 6, 541 - 549, 04.11.2021
https://doi.org/10.18621/eurj.855510

Abstract

References

  • 1. Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol 2020;95:548-67.
  • 2. Bergsagel DE, Sprague CC, Austin C, Griffith KM. Evaluation of new chemotherapeutic agents in the treatment of multiple myeloma: IV. L-Phenylalanine mustard (NSC-8806). Cancer Chemother Rep 1962;21:87-99.
  • 3. Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. N Engl J Med 1996;335:91-7.
  • 4. Morgan GJ1, Davies FE. Role of thalidomide in the treatment of patients with multiple myeloma. Crit Rev Oncol Hematol 2013;88 Suppl 1:S14-22.
  • 5. Abe Y , Ishida T. Immunomodulatory drugs in the treatment of multiple myeloma. Jpn J Clin Oncol 2019;49:695-702.
  • 6. Touzeau C, Moreau P. Daratumumab for the treatment of multiple myeloma. Expert Opin Biol Ther 2017;17:887-93.
  • 7. Pamukçuoğlu M, Emmez H, Tunçcan OG, Oner AY, Cırak MY, Senol E, et al. Brain abscess caused by Nocardia cyriacigeorgica in two patients with multiple myeloma: novel agents, new spectrum of infections. Hematology 2014;19:158-62.
  • 8. Kim SJ, Kim K, Kim BS, Lee HJ, Kim H, Lee NR, et al. Bortezomib and the increased incidence of herpes zoster in patients with multiple myeloma. Clin Lymphoma Myeloma 2008;8:237-40.
  • 9. Basler M, Lauer C, Beck U, Groettrup M. The proteasome inhibitor bortezomib enhances the susceptibility to viral infection. J Immunol 2009;183:6145-50.
  • 10. Tung D, Cheung PH, Kaur P, Foreman O, Kavirayani A, Hain HS, et al. Anti-inflammatory and immunomodulatory effects of bortezomib in various in vivo models. Pharmacology 2011;88:100-13.
  • 11. Wu KL, van Wieringen W, Vellenga E, Zweegman S, Lokhorst HM, Sonneveld P. Analysis of the efficacy and toxicity of bortezomib for treatment of relapsed or refractory multiple myeloma in community practice. Haematologica 2005;90:996-7.
  • 12. Greipp PR, Miguel JS, Durie BGM, Crowley JJ, Barlogie B, Blad J, et al. International staging system for multiple myeloma. J Clin Oncol 2005;23:3412-20.
  • 13. Palumbo A, Loiseau HA, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, et al. Revised International Staging System for Multiple Myeloma: a report From International Myeloma Working Group. J Clin Oncol 2015;33:2863-9.
  • 14. Kropff M, Bisping G, Schuck E, Liebisch P, Lang N, Hentrich M, et al. Bortezomib in combination with intermediate-dose dexamethasone and continuous low-dose oral cyclophosphamide for relapsed multiple myeloma. Br J Haematol 2007;138:330-7.
  • 15. Pang Y, Shao H, Yang Z, Fan L, Liu W, Shi J, et al. The neutrophils+monocyte/lymphocyte ratio is an independent prognostic factor for progression-free survival in newly diagnosed multiple myeloma patients treated with BCD regimen. Front Oncol 2020;10:1617.
  • 16. Zeng Q, Liu Z, Li Q, Liu T. Prognostic value of neutrophil to lymphocyte ratio and clinicopathological characteristics for multiple myeloma. Medicine (Baltimore). 2018;97:e12678.
  • 17. Suriu C, Akria L, Azoulay D, Shaoul E, Barhoum M, Braester A. Absolute lymphocyte count as prognostic marker in newly diagnosed multiple myeloma patients. Int J Lab Hematol 2016;38:e56-9.
  • 18. Romano A, Parrinello NL, Consoli ML, Marchionni L, Forte S, Conticello C, et al. Neutrophil to lymphocyte ratio (NLR) improves the risk assessment of ISS staging in newly diagnosed MM patients treated upfront with novel agents. Ann Hematol 2015;94:1875-83.
  • 19. Wang J, Sun C, Xia J, Zhou X, Guo HF. Limited prognostic value of pretreatment neutrophil-to-lymphocyte ratios in elderly patients with multiple myeloma. Clin Lab 2018;64:507-13.
  • 20. Romano A, Laura PN, Cerchione C, Letizia CM, Parisi M, Calafiore V, et al. The NLR and LMR ratio in newly diagnosed MM patients treated upfront with novel agents. Blood Cancer J 2017;7:649.
  • 21. Raje N, Berdeja J, Lin Y, Siegel D, Jagannath S, Madduri D, et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N Engl J Med 2019;380:1726-37.
  • 22. Binder M, Rajkumar SV, Lacy MQ, Gertz MA, Buadi FK, Dispenzieri A, et al. Peripheral blood biomarkers of early immune reconstitution in newly diagnosed multiple myeloma. Am J Hematol 2019; 94:306-11.
  • 23. Ueda T, Chikuie N, Takumida M, Furuie H, Kono T, Taruya T, et al. Baseline neutrophil-to-lymphocyte ratio (NLR) is associated with clinical outcome in recurrent or metastatic head and neck cancer patients treated with nivolumab. Acta Otolaryngol 2020;140:181-7.
  • 24. Kosuga T, Konishi T, Kubota T, Shoda K, Konishi H, Shiozaki A, et al. Clinical significance of neutrophil-to-lymphocyte ratio as a predictor of lymph node metastasis in gastric cancer. BMC Cancer 2019;19:1187.
  • 25. Bento L, Díaz-López A, Barranco G, Martín-Moreno AM, Baile M, Martín A, et al. New prognosis score including absolute lymphocyte/monocyte ratio, red blood cell distribution width and beta-2 microglobulin in patients with diffuse large B-cell lymphoma treated with R-CHOP: Spanish Lymphoma Group Experience (GELTAMO). Br J Haematol 2020;188:888-97.
  • 26. Dosani T, Covut F, Beck R, Driscoll JJ, de Lima M, Malek E. Significance of the absolute lymphocyte/monocyte ratio as a prognostic immune biomarker in newly diagnosed multiple myeloma. Blood Cancer J 2017;7:e579.
  • 27. Yang Y, Liu Z, Wang H. Peripheral absolute lymphocyte count: an economical and clinical available immune-related prognostic marker for newly diagnosed multiple myeloma. Med Sci Monit 2020;26:e923716.
There are 27 citations in total.

Details

Primary Language English
Subjects Haematology, Clinical Sciences
Journal Section Original Articles
Authors

Merve Pamukcuoglu 0000-0002-4591-2025

Nuran Ahu Baysal This is me 0000-0003-4304-9245

Mehmet Sezgin Pepeler 0000-0002-2762-8573

Publication Date November 4, 2021
Submission Date January 7, 2021
Acceptance Date February 5, 2021
Published in Issue Year 2021 Volume: 7 Issue: 6

Cite

AMA Pamukcuoglu M, Baysal NA, Pepeler MS. The infection rate in new diagnosis and relapsed/refractory multiple myeloma patients who had bortezomib-based chemotherapy and relationship between development of infection and lymphocyte/monocyte ratio. Eur Res J. November 2021;7(6):541-549. doi:10.18621/eurj.855510

e-ISSN: 2149-3189 


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