ASSESSMENT OF TREATMENT OUTCOMES IN MULTIPLE MYELOMA ACCORDING TO PROGNOSTIC FACTORS AND THERAPEUTIC APPROACH
Keywords:
multiple myeloma, prognostic factors, risk stratification, therapeutic protocols, treatment outcome
Abstract
Introduction/Aim. Multiple myeloma is a malignant plasma cell disorder characterized by clonal proliferation of abnormal plasma cells. Global five-year survival rates range from 60% to 70%, largely due to novel therapeutic strategies. In our country, conventional therapies remain standard, with monoclonal antibodies recently introduced for relapsed/refractory cases. This study aimed to assess treatment outcomes in relation to therapy type and prognostic factors.
Pathients and Methods. A retrospective – prospective analysis was conducted on 200 patients with multiple myeloma. The relationship between treatment modality, disease biology, clinical status, and therapeutic response was evaluated, including progression-free survival (PFS), overall survival (OS), and protocol efficacy across prognostic subgroups.
Results. Best treatment responses were achieved in patients with good performance status and low comorbidity, particularly those receiving first-line VTD (bortezomib, thalidomide, dexamethasone). Among patients under 65, the CTD (cyclophosphamide, thalidomide, dexamethasone) protocol showed the longest average OS. In second-line therapy, PAD (bortezomib, doxorubicin, dexamethasone) yielded the highest response rates and best survival outcomes. Elderly patients with high Charlson Comorbidity Index (CCI) benefited most from the MPT regimen (melphalan, prednisone, thalidomide). In contrast, Vel-Dex (bortezomib, dexamethasone) was linked to the highest progression rates.
Conclusion. Therapeutic outcome in myeloma strongly correlates with prognostic factors and treatment selection. Proper risk stratification enables personalized therapy and improves outcome.
Keywords: multiple myeloma, prognostic factors, risk stratification, therapeutic protocols, treatment outcome
References
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10. Jurczyszyn A, Nahi H, Avivi I. Characteristics and outcomes of patients with multiple myeloma aged 21-40 years versus 41-60 years: a multi-institutional case-control study. Br J Haematol. 2016; 175(5):884-891.
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12. Boyd KD, Ross FM, Tapper WJ, Chiecchio L, Dagrada GP, Konn ZJ, et al. Gender disparities in the tumor genetics and clinical outcome of multiple myeloma. Cancer Epidemiol Biomarkers Prev. 2011 Aug;20(8):1703-7.
13. Pawlyn C, Melchor L, Murison A, Wardell CP, Manwani D, Kaiser MF, et al. Gender influences the molecular and clinical features of multiple myeloma at diagnosis. Haematologica. 2021 Aug 1;106(8):2163-73.
14. Ozerova M, Nefedova Y. Estrogen promotes multiple myeloma through enhancing the immunosuppressive activity of MDSC. Leuk Lymphoma. 2019 Jan 2;60(6):1557–62.
15. Spasov S, Goranova-Marinova V, Konstantinov SM, Spasova N, Topouzov M. Survival of patients with multiple myeloma depends on renal impairment at diagnosis. J BUON. 2005 Apr-Jun;10(2):239-42.
16. Jang H, Park H, Kim YK, Kim HJ, Kim WS, Kim K, et al. Improved survival of patients with multiple myeloma in the era of novel agents: a population-based study in Korea. Blood Cancer J. 2022 May 6;12(5):72.
17. Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, et al. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015 Mar 12;125(13):2068-74.
18. Yin X, Fan F, Zhang B, Hu Y, Sun C. Cardiovascular-specific mortality among multiple myeloma patients: a population-based study. Ther Adv Hematol. 2022 Mar 31;13:20406207221086755.
19. 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. N Engl J Med. 1996 Jul 11;335(2):91-7.
20. Antlanger M, Dust T, Reiter T, Böhm A, Lamm WW, Gornicec M, et al. Impact of renal impairment on outcomes after autologous stem cell transplantation in multiple myeloma: a multi center, retrospective cohort study. BMC Cancer. 2018;18:1008.
21. Kushwaha N, Kumar S, Sheikh MA, Philip J, Sharma S, Biswas AK, et al. Association of CD34 positive cell dose with engraftment kinetics in autologous peripheral blood stem cell transplant patients of multiple myeloma. Med J Armed Forces India. 2021;78(3):296–301.
22. Kim JS, Kim K, Cheong JW, Min YH, Suh C, Kim H, et al. Complete remission status before autologous stem cell transplantation is an important prognostic factor in patients with multiple myeloma undergoing upfront single autologous transplantation. Biol Blood Marrow Transplant. 2009;15(4):463–70.
23. Qin X, Xu Y, An G, Qin Y, Feng X, Sui W, Deng S, Zang M, Lyu R, Wang T, Li Z, Yi S, Qiu L. The impact of renal function on prognostic value of β₂-microglobulin of ISS stage system in multiple myeloma patients--Clinical data analysis of 666 patients in a single center. Zhonghua Xue Ye Xue Za Zhi. 2015 May;36(5):393-7.
24. Walker BA, Mavrommatis K, Wardell CP, Ashby TC, Bauer M, Davies F et al. A high-risk, Double-Hit, group of newly diagnosed myeloma identified by genomic analysis. Leukemia. 2019 Jan;33(1):159-170.
25. Hanamura I. Multiple myeloma with high-risk cytogenetics and its treatment approach. Int J Hematol. 2022 Jun;115(6):762-777.
26. San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, et al. Bortezomib plus melphalan and prednisone significantly prolongs time to progression versus melphalan and prednisone in newly diagnosed, transplant ineligible multiple myeloma: results of the phase III VISTA trial. J Clin Oncol. 2008;26(13):2137-43.
27. Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch A, Cavo M, et al. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014;371(10):906-17.
28. Durie BG, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, et al. Bortezomib, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017;389(10068):519-27.
29. Vasquez J, Ruiz R, Aliaga K, et al. Cyclophosphamide, Thalidomide, and Dexamethasone (CTD) as Initial Therapy for Patients with Newly Diagnosed Multiple Myeloma in a Middle-Income Country: 7-Year Follow-Up. JCO Glob Oncol. 2021;7:1199-1205.
30. Mikhael JR, Reeder CB, Libby EN, et al. Phase Ib/II trial of CYKLONE (cyclophosphamide, carfilzomib, thalidomide and dexamethasone) for newly diagnosed myeloma. Br J Haematol. 2015 Apr;169(2):219-27.
31. Hulin C, Dimopoulos MA, Dispenzieri A, et al. Continuous lenalidomide and low-dose dexamethasone in transplant-ineligible patients with newly diagnosed multiple myeloma. N Engl J Med. 2014;371(10):906-917.
32. Palumbo A, Bringhen S, Caravita T, et al. Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood. 2008 Oct 15;112(8):3107-14.
33. San-Miguel JF, Vidriales MB, Cibeira MT, et al. Superiority of bortezomib, thalidomide, and dexamethasone over thalidomide and dexamethasone or VBMCP/VBAD/B in previously untreated multiple myeloma: PETHEMA/GEM clinical trial. Blood. 2012 Aug 23;120(8):1589-96.
34. Kiba T, Kawano Y, Takahashi K, et al. Retrospective analysis of bortezomib and dexamethasone combination therapy in multiple myeloma patients. BMC Cancer. 2014 Jul 4;14:462.
35. Zhang W, Wang Y, Ma X, et al. Efficacy of bortezomib, doxorubicin, and dexamethasone (PAD) in relapsed/refractory multiple myeloma patients with extramedullary disease: a retrospective study. Leuk Lymphoma. 2018;59(2):422-429.
36. Lonial S, Lee HC, Badros A, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, multicentre, phase 2 trial. Lancet. 2016 Jan 23;387(10027):1551-60.
37. Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2021 Jun 3;384(8):705-716.
38. Cho SF, Anderson KC, Tai YT. T-cell redirecting bispecific antibodies targeting BCMA for multiple myeloma treatment. Immunotherapy. 2020 Sep;12(12):963-973.
39. Lonial S, Lee HC, Wang H, et al. Belantamab Mafodotin for Relapsed or Refractory Multiple Myeloma (DREAMM-2): A Two-Arm, Randomised, Open-Label, Phase 2 Study. Lancet Oncol. 2020 Feb;21(2):207-221.
40. Costa LJ, Shain KH, Shih A, et al. Emerging therapies for multiple myeloma: an update. Expert Opin Investig Drugs. 2021;30(8):779-796.
41. Perrot A, Lauwers-Cances V, Tournay E, et al. Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma. Blood. 2018 Jan 11;132(23):2456-2464.
42. Landgren O, Iskander K. Minimal Residual Disease in Multiple Myeloma: Current Landscape and Future Applications With Immunotherapeutic Approaches. Front Oncol. 2020;10:664.
43. Perrot A, Tournay E, Lauwers-Cances V, et al. Measurable Residual Disease–Guided Therapy in Newly Diagnosed Multiple Myeloma. N Engl J Med. 2025 Jun 12;392(24):2296-2308.
2. Bowcock S, Atkin C, Iqbal G, Pratt G, Yong K, Neal RD, Planche T, Karunanithi K, Jenkins S, Stern S, Arnott S, Toth P, Wandroo F, Dunn J, Drayson MT; TEAMM Trial Management Group and Trial Investigators. Presenting Symptoms in Newly Diagnosed Myeloma, Relation to Organ Damage, and Implications for Symptom-Directed Screening: A Secondary Analysis from the Tackling Early Morbidity and Mortality in Myeloma (TEAMM) Trial. Cancers (Basel). 2023 Jun 25;15(13):3337.
3. Mitrović M, Sretenović A, Bila J .The significance of prognostic profiling in the treatment of patients with multiple myeloma. Medicinski podmladak 2020, 71(4):17-24.
4. Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, et al. Revised international staging system for multi¬ple myeloma: A report from international myeloma working group. J Clin Oncol. 2015 Sep 10;33(26):2863-9.
5. Wang, J., Li, J., Zhang, R.et al. Real-world prognostic significance of attaining minimal residual disease negativity in newly diagnosed multiple myeloma. Discov Oncol. 2024 Feb 17;15(1):38.
6. Dimopoulos MA, Moreau P, Terpos E, Mateos MV, Zweegman S, Cook G, et al. Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32(3):309-322.
7. Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011 Mar 17;364(11):1046-60.
8. Fischer J, Knop S, Danhof S, et al. The influence of baseline characteristics, treatment and depression on health-related quality of life in patients with multiple myeloma: A prospective observational study. Research Square; 2022.
9. Caulier A, Roussel M, Morel P. Epidemiological landscape of young patients with multiple myeloma diagnosed before 40 years of age: the French experience. Blood. 2021; 138(25):2686-2695.
10. Jurczyszyn A, Nahi H, Avivi I. Characteristics and outcomes of patients with multiple myeloma aged 21-40 years versus 41-60 years: a multi-institutional case-control study. Br J Haematol. 2016; 175(5):884-891.
11. Bird S, Cairns D, Menzies T, Boyd K, Davies F, Cook G, Drayson M, Gregory W, Jenner M, Jones J, Kaiser M, Owen R, Jackson G, Morgan G, Pawlyn C. Sex Differences in Multiple Myeloma Biology but not Clinical Outcomes: Results from 3894 Patients in the Myeloma XI Trial. Clin Lymphoma Myeloma Leuk. 2021 Oct;21(10):667-675.
12. Boyd KD, Ross FM, Tapper WJ, Chiecchio L, Dagrada GP, Konn ZJ, et al. Gender disparities in the tumor genetics and clinical outcome of multiple myeloma. Cancer Epidemiol Biomarkers Prev. 2011 Aug;20(8):1703-7.
13. Pawlyn C, Melchor L, Murison A, Wardell CP, Manwani D, Kaiser MF, et al. Gender influences the molecular and clinical features of multiple myeloma at diagnosis. Haematologica. 2021 Aug 1;106(8):2163-73.
14. Ozerova M, Nefedova Y. Estrogen promotes multiple myeloma through enhancing the immunosuppressive activity of MDSC. Leuk Lymphoma. 2019 Jan 2;60(6):1557–62.
15. Spasov S, Goranova-Marinova V, Konstantinov SM, Spasova N, Topouzov M. Survival of patients with multiple myeloma depends on renal impairment at diagnosis. J BUON. 2005 Apr-Jun;10(2):239-42.
16. Jang H, Park H, Kim YK, Kim HJ, Kim WS, Kim K, et al. Improved survival of patients with multiple myeloma in the era of novel agents: a population-based study in Korea. Blood Cancer J. 2022 May 6;12(5):72.
17. Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, et al. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015 Mar 12;125(13):2068-74.
18. Yin X, Fan F, Zhang B, Hu Y, Sun C. Cardiovascular-specific mortality among multiple myeloma patients: a population-based study. Ther Adv Hematol. 2022 Mar 31;13:20406207221086755.
19. 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. N Engl J Med. 1996 Jul 11;335(2):91-7.
20. Antlanger M, Dust T, Reiter T, Böhm A, Lamm WW, Gornicec M, et al. Impact of renal impairment on outcomes after autologous stem cell transplantation in multiple myeloma: a multi center, retrospective cohort study. BMC Cancer. 2018;18:1008.
21. Kushwaha N, Kumar S, Sheikh MA, Philip J, Sharma S, Biswas AK, et al. Association of CD34 positive cell dose with engraftment kinetics in autologous peripheral blood stem cell transplant patients of multiple myeloma. Med J Armed Forces India. 2021;78(3):296–301.
22. Kim JS, Kim K, Cheong JW, Min YH, Suh C, Kim H, et al. Complete remission status before autologous stem cell transplantation is an important prognostic factor in patients with multiple myeloma undergoing upfront single autologous transplantation. Biol Blood Marrow Transplant. 2009;15(4):463–70.
23. Qin X, Xu Y, An G, Qin Y, Feng X, Sui W, Deng S, Zang M, Lyu R, Wang T, Li Z, Yi S, Qiu L. The impact of renal function on prognostic value of β₂-microglobulin of ISS stage system in multiple myeloma patients--Clinical data analysis of 666 patients in a single center. Zhonghua Xue Ye Xue Za Zhi. 2015 May;36(5):393-7.
24. Walker BA, Mavrommatis K, Wardell CP, Ashby TC, Bauer M, Davies F et al. A high-risk, Double-Hit, group of newly diagnosed myeloma identified by genomic analysis. Leukemia. 2019 Jan;33(1):159-170.
25. Hanamura I. Multiple myeloma with high-risk cytogenetics and its treatment approach. Int J Hematol. 2022 Jun;115(6):762-777.
26. San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, et al. Bortezomib plus melphalan and prednisone significantly prolongs time to progression versus melphalan and prednisone in newly diagnosed, transplant ineligible multiple myeloma: results of the phase III VISTA trial. J Clin Oncol. 2008;26(13):2137-43.
27. Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch A, Cavo M, et al. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014;371(10):906-17.
28. Durie BG, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, et al. Bortezomib, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017;389(10068):519-27.
29. Vasquez J, Ruiz R, Aliaga K, et al. Cyclophosphamide, Thalidomide, and Dexamethasone (CTD) as Initial Therapy for Patients with Newly Diagnosed Multiple Myeloma in a Middle-Income Country: 7-Year Follow-Up. JCO Glob Oncol. 2021;7:1199-1205.
30. Mikhael JR, Reeder CB, Libby EN, et al. Phase Ib/II trial of CYKLONE (cyclophosphamide, carfilzomib, thalidomide and dexamethasone) for newly diagnosed myeloma. Br J Haematol. 2015 Apr;169(2):219-27.
31. Hulin C, Dimopoulos MA, Dispenzieri A, et al. Continuous lenalidomide and low-dose dexamethasone in transplant-ineligible patients with newly diagnosed multiple myeloma. N Engl J Med. 2014;371(10):906-917.
32. Palumbo A, Bringhen S, Caravita T, et al. Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood. 2008 Oct 15;112(8):3107-14.
33. San-Miguel JF, Vidriales MB, Cibeira MT, et al. Superiority of bortezomib, thalidomide, and dexamethasone over thalidomide and dexamethasone or VBMCP/VBAD/B in previously untreated multiple myeloma: PETHEMA/GEM clinical trial. Blood. 2012 Aug 23;120(8):1589-96.
34. Kiba T, Kawano Y, Takahashi K, et al. Retrospective analysis of bortezomib and dexamethasone combination therapy in multiple myeloma patients. BMC Cancer. 2014 Jul 4;14:462.
35. Zhang W, Wang Y, Ma X, et al. Efficacy of bortezomib, doxorubicin, and dexamethasone (PAD) in relapsed/refractory multiple myeloma patients with extramedullary disease: a retrospective study. Leuk Lymphoma. 2018;59(2):422-429.
36. Lonial S, Lee HC, Badros A, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, multicentre, phase 2 trial. Lancet. 2016 Jan 23;387(10027):1551-60.
37. Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2021 Jun 3;384(8):705-716.
38. Cho SF, Anderson KC, Tai YT. T-cell redirecting bispecific antibodies targeting BCMA for multiple myeloma treatment. Immunotherapy. 2020 Sep;12(12):963-973.
39. Lonial S, Lee HC, Wang H, et al. Belantamab Mafodotin for Relapsed or Refractory Multiple Myeloma (DREAMM-2): A Two-Arm, Randomised, Open-Label, Phase 2 Study. Lancet Oncol. 2020 Feb;21(2):207-221.
40. Costa LJ, Shain KH, Shih A, et al. Emerging therapies for multiple myeloma: an update. Expert Opin Investig Drugs. 2021;30(8):779-796.
41. Perrot A, Lauwers-Cances V, Tournay E, et al. Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma. Blood. 2018 Jan 11;132(23):2456-2464.
42. Landgren O, Iskander K. Minimal Residual Disease in Multiple Myeloma: Current Landscape and Future Applications With Immunotherapeutic Approaches. Front Oncol. 2020;10:664.
43. Perrot A, Tournay E, Lauwers-Cances V, et al. Measurable Residual Disease–Guided Therapy in Newly Diagnosed Multiple Myeloma. N Engl J Med. 2025 Jun 12;392(24):2296-2308.
Published
2025/11/19
Section
Originalni rad / Original article