Skip to main content

Advertisement

Log in

Clinical outcomes and prognostic factors in patients with multiple myeloma in South Tyrol: a retrospective single-center analysis

Annals of Hematology Aims and scope Submit manuscript

Abstract

High-dose chemotherapy followed by autologous stem cell transplantation (HD-ASCT) as well as the introduction of novel agents (NA) significantly improved survival for patients with multiple myeloma (MM). A total of 150 unselected newly diagnosed MM patients treated at our institution from 1998 to 2017 were retrospectively analyzed. Median age at diagnosis was 69 years (range 33–93 years) with a median follow-up of 48.6 months. The median overall survival (OS) for the entire cohort was 60.7 months (range 0.3–280.1). Patients who received frontline HD-ASCT (p < 0.01) or NA-based first-line treatment (p = 0.043) had a significantly better OS. According to the revised Myeloma Comorbidity Index (R-MCI), patients were defined as fit (36.5%), intermediate-fit (44.5%), or frail (19%) with a significant difference in OS between these categories (p < 0.01). Multivariate analysis revealed R-MCI as an independent prognostic factor for OS (p < 0.01). Presence of subclinical amyloid deposits (A+) was detected in 18 out of 66 patients (27.3%) and significantly correlated with a serum free light chain (sFLC) ratio ≥ 100 (p = 0.01) and bone marrow plasma cell infiltration > 60% (p = 0.04). Furthermore, patients with A+ had significantly worse OS compared with their counterparts (p = 0.048). Our results corroborate the efficacy of both early HD-ASCT and the use of new agents as initial therapy of MM patients in “real-world” daily clinical practice. The R-MCI is an easily applicable tool to stratify MM patients and may support treatment decisions. The prognostic value of subclinical amyloid deposition should be validated within prospective studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68:7–30. https://doi.org/10.3322/caac.21442

    Article  PubMed  Google Scholar 

  2. Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A, Fonseca R, Rajkumar SV, Offord JR, Larson DR, Plevak ME, Therneau TM, Greipp PR (2003) Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 78:21–33. https://doi.org/10.4065/78.1.21

    Article  PubMed  Google Scholar 

  3. Palumbo A, Anderson K (2011) Multiple myeloma. N Engl J Med 364:1046–1060. https://doi.org/10.1056/NEJMra1011442

    Article  CAS  PubMed  Google Scholar 

  4. Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S, Kapoor P, Dingli D, Hayman SR, Leung N, Lust J, McCurdy A, Russell SJ, Zeldenrust SR, Kyle RA, Rajkumar SV (2014) Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia 28:1122–1128. https://doi.org/10.1038/leu.2013.313

    Article  CAS  PubMed  Google Scholar 

  5. Pulte D, Gondos A, Brenner H (2011) Improvement in survival of older adults with multiple myeloma: results of an updated period analysis of SEER data. Oncologist 16:1600–1603. https://doi.org/10.1634/theoncologist.2011-0229

    Article  PubMed  PubMed Central  Google Scholar 

  6. Gay F, Oliva S, Petrucci MT, Conticello C, Catalano L, Corradini P, Siniscalchi A, Magarotto V, Pour L, Carella A, Malfitano A, Petrò D, Evangelista A, Spada S, Pescosta N, Omedè P, Campbell P, Liberati AM, Offidani M, Ria R, Pulini S, Patriarca F, Hajek R, Spencer A, Boccadoro M, Palumbo A (2015) Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial. Lancet Oncol 16:1617–1629. https://doi.org/10.1016/S1470-2045(15)00389-7

    Article  CAS  PubMed  Google Scholar 

  7. Deschler B, Binek K, Ihorst G et al (2010) Prognostic factor and quality of life analysis in 160 patients aged > or =60 years with hematologic neoplasias treated with allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 16:967–975. https://doi.org/10.1016/j.bbmt.2010.02.004

    Article  PubMed  Google Scholar 

  8. Newberry KJ, Naqvi K, Nguyen KT, Cardenas-Turanzas M, Florencia Tanaka M, Pierce S, Verstovsek S (2014) Comorbidities predict worse prognosis in patients with primary myelofibrosis. Cancer 120:2996–3002. https://doi.org/10.1002/cncr.28857

    Article  PubMed  Google Scholar 

  9. Antic D, Jelicic J, Trajkovic G, Balint MT, Bila J, Markovic O, Petkovic I, Nikolic V, Andjelic B, Djurasinovic V, Sretenovic A, Smiljanic M, Vukovic V, Mihaljevic B (2018) Is it possible to improve prognostic value of NCCN-IPI in patients with diffuse large B cell lymphoma? The prognostic significance of comorbidities. Ann Hematol 97:267–276. https://doi.org/10.1007/s00277-017-3170-z

    Article  CAS  PubMed  Google Scholar 

  10. Kleber M, Ihorst G, Deschler B, Jakob C, Liebisch P, Koch B, Sezer O, Engelhardt M (2009) Detection of renal impairment as one specific comorbidity factor in multiple myeloma: multicenter study in 198 consecutive patients. Eur J Haematol 83:519–527. https://doi.org/10.1111/j.1600-0609.2009.01318.x

    Article  CAS  PubMed  Google Scholar 

  11. Wasterlid T, Mohammadi M, Smedby KE et al (2019) Impact of comorbidity on disease characteristics, treatment intent and outcome in diffuse large B-cell lymphoma: a Swedish lymphoma register study. J Intern Med 285:455–468. https://doi.org/10.1111/joim.12849

    Article  CAS  PubMed  Google Scholar 

  12. Engelhardt M, Domm A-S, Dold SM, Ihorst G, Reinhardt H, Zober A, Hieke S, Baayen C, Müller SJ, Einsele H, Sonneveld P, Landgren O, Schumacher M, Wäsch R (2017) A concise revised Myeloma Comorbidity Index as a valid prognostic instrument in a large cohort of 801 multiple myeloma patients. Haematologica 102:910–921. https://doi.org/10.3324/haematol.2016.162693

    Article  PubMed  PubMed Central  Google Scholar 

  13. Bhat A, Selmi C, Naguwa SM, Cheema GS, Gershwin ME (2010) Currents concepts on the immunopathology of amyloidosis. Clin Rev Allergy Immunol 38:97–106. https://doi.org/10.1007/s12016-009-8163-9

    Article  PubMed  Google Scholar 

  14. Falk RH, Comenzo RL, Skinner M (1997) The systemic amyloidoses. N Engl J Med 337:898–909. https://doi.org/10.1056/NEJM199709253371306

    Article  CAS  PubMed  Google Scholar 

  15. Puchtler H, Sweat F (1965) Congo red as a stain for fluorescence microscopy of amyloid. J Histochem Cytochem 13:693–694. https://doi.org/10.1177/13.8.693

    Article  CAS  PubMed  Google Scholar 

  16. Glenner GG, Ein D, Eanes ED, Bladen HA, Terry W, Page DL (1971) Creation of “amyloid” fibrils from Bence Jones proteins in vitro. Science 174:712–714

    Article  CAS  PubMed  Google Scholar 

  17. Sonneveld P, Avet-Loiseau H, Lonial S, Usmani S, Siegel D, Anderson KC, Chng WJ, Moreau P, Attal M, Kyle RA, Caers J, Hillengass J, San Miguel J, van de Donk N, Einsele H, Bladé J, Durie BG, Goldschmidt H, Mateos MV, Palumbo A, Orlowski R (2016) Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. Blood 127:2955–2962. https://doi.org/10.1182/blood-2016-01-631200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bender R, Lange S (2001) Adjusting for multiple testing - when and how? J Clin Epidemiol 54:343–349. https://doi.org/10.1016/S0895-4356(00)00314-0

    Article  CAS  PubMed  Google Scholar 

  19. Gertz MA (2018) Immunoglobulin light chain amyloidosis: 2018 update on diagnosis, prognosis, and treatment. Am J Hematol 93:1169–1180. https://doi.org/10.1002/ajh.25149

    Article  CAS  PubMed  Google Scholar 

  20. Gay F, Engelhardt M, Terpos E, Wäsch R, Giaccone L, Auner HW, Caers J, Gramatzki M, van de Donk N, Oliva S, Zamagni E, Garderet L, Straka C, Hajek R, Ludwig H, Einsele H, Dimopoulos M, Boccadoro M, Kröger N, Cavo M, Goldschmidt H, Bruno B, Sonneveld P (2018) From transplant to novel cellular therapies in multiple myeloma: European Myeloma Network guidelines and future perspectives. Haematologica 103:197–211. https://doi.org/10.3324/haematol.2017.174573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Costa LJ, Hari PN, Kumar SK (2016) Differences between unselected patients and participants in multiple myeloma clinical trials in US: a threat to external validity. Leuk Lymphoma 57:2827–2832. https://doi.org/10.3109/10428194.2016.1170828

    Article  PubMed  Google Scholar 

  22. Hock BD, Mulholland KS, Ganly P et al (2018) Impact of increased access to novel agents on the survival of multiple myeloma patients treated at a single New Zealand centre. Intern Med J. https://doi.org/10.1111/imj.14155

  23. Thoennissen GB, Gorlich D, Bacher U et al (2017) Autologous stem cell transplantation in multiple myeloma in the era of novel drug induction: a retrospective single-center analysis. Acta Haematol 137:163–172. https://doi.org/10.1159/000463534

    Article  CAS  PubMed  Google Scholar 

  24. Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Zeldenrust SR, Dingli D, Russell SJ, Lust JA, Greipp PR, Kyle RA, Gertz MA (2008) Improved survival in multiple myeloma and the impact of novel therapies. Blood 111:2516–2520. https://doi.org/10.1182/blood-2007-10-116129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Pozzi S, Marcheselli L, Bari A, Liardo EV, Marcheselli R, Luminari S, Quaresima M, Cirilli C, Ferri P, Federico M, Sacchi S (2013) Survival of multiple myeloma patients in the era of novel therapies confirms the improvement in patients younger than 75 years: a population-based analysis. Br J Haematol 163:40–46. https://doi.org/10.1111/bjh.12465

    Article  PubMed  Google Scholar 

  26. Tangen J-M, Tjonnfjord GE, Gulbrandsen N et al (2018) Improved outcome in patients following autologous stem cell transplantation for multiple myeloma in south eastern Norway 2001-2010: a retrospective, population based analysis. BMC Cancer 18:801. https://doi.org/10.1186/s12885-018-4722-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Warren JL, Harlan LC, Stevens J, Little RF, Abel GA (2013) Multiple myeloma treatment transformed: a population-based study of changes in initial management approaches in the United States. J Clin Oncol 31:1984–1989. https://doi.org/10.1200/JCO.2012.46.3323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Mey UJM, Leitner C, Driessen C, Cathomas R, Klingbiel D, Hitz F (2016) Improved survival of older patients with multiple myeloma in the era of novel agents. Hematol Oncol 34:217–223. https://doi.org/10.1002/hon.2205

    Article  PubMed  Google Scholar 

  29. Remes K, Anttila P, Silvennoinen R et al (2018) Real-world treatment outcomes in multiple myeloma: multicenter registry results from Finland 2009-2013. PLoS One 13:e0208507. https://doi.org/10.1371/journal.pone.0208507

    Article  PubMed  PubMed Central  Google Scholar 

  30. Yong K, Delforge M, Driessen C, Fink L, Flinois A, Gonzalez-McQuire S, Safaei R, Karlin L, Mateos MV, Raab MS, Schoen P, Cavo M (2016) Multiple myeloma: patient outcomes in real-world practice. Br J Haematol 175:252–264. https://doi.org/10.1111/bjh.14213

    Article  PubMed  PubMed Central  Google Scholar 

  31. Raab MS, Cavo M, Delforge M, Driessen C, Fink L, Flinois A, Gonzalez-McQuire S, Safaei R, Karlin L, Mateos MV, Schoen P, Yong K (2016) Multiple myeloma: practice patterns across Europe. Br J Haematol 175:66–76. https://doi.org/10.1111/bjh.14193

    Article  PubMed  Google Scholar 

  32. Raab MS, Fink L, Schoen P et al (2018) Evolution of multiple myeloma treatment practices in Europe from 2014 to 2016. Br J Haematol. https://doi.org/10.1111/bjh.15680

  33. Fermand JP, Ravaud P, Chevret S, Divine M, Leblond V, Belanger C, Macro M, Pertuiset E, Dreyfus F, Mariette X, Boccacio C, Brouet JC (1998) High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial. Blood 92:3131–3136

    Article  CAS  PubMed  Google Scholar 

  34. Blade J, Rosinol L, Sureda A et al (2005) High-dose therapy intensification compared with continued standard chemotherapy in multiple myeloma patients responding to the initial chemotherapy: long-term results from a prospective randomized trial from the Spanish cooperative group PETHEMA. Blood 106:3755–3759. https://doi.org/10.1182/blood-2005-03-1301

    Article  CAS  PubMed  Google Scholar 

  35. Fermand J-P, Katsahian S, Divine M, Leblond V, Dreyfus F, Macro M, Arnulf B, Royer B, Mariette X, Pertuiset E, Belanger C, Janvier M, Chevret S, Brouet JC, Ravaud P, Group Myelome-Autogreffe (2005) High-dose therapy and autologous blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: long-term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol 23:9227–9233. https://doi.org/10.1200/JCO.2005.03.0551

    Article  CAS  PubMed  Google Scholar 

  36. Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, Brown J, Drayson MT, Selby PJ, Medical Research Council Adult Leukaemia Working Party (2003) High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 348:1875–1883. https://doi.org/10.1056/NEJMoa022340

    Article  CAS  PubMed  Google Scholar 

  37. Dhakal B, Szabo A, Chhabra S, Hamadani M, D’Souza A, Usmani SZ, Sieracki R, Gyawali B, Jackson JL, Asimakopoulos F, Hari PN (2018) Autologous transplantation for newly diagnosed multiple myeloma in the era of novel agent induction: a systematic review and meta-analysis. JAMA Oncol 4:343–350. https://doi.org/10.1001/jamaoncol.2017.4600

    Article  PubMed  PubMed Central  Google Scholar 

  38. Su B, Zhu X, Jiang Y et al (2018) A meta-analysis of autologous transplantation for newly diagnosed multiple myeloma in the era of novel agents. Leuk Lymphoma:1–8. https://doi.org/10.1080/10428194.2018.1543874

  39. Musto P, Anderson KC, Attal M et al (2017) Second primary malignancies in multiple myeloma: an overview and IMWG consensus. Ann Oncol 28:228–245. https://doi.org/10.1093/annonc/mdw606

    Article  CAS  PubMed  Google Scholar 

  40. Sahebi F, Iacobelli S, Sbianchi G, Koster L, Blaise D, Reményi P, Russell NH, Ljungman P, Kobbe G, Apperley J, Trneny M, Krejci M, Wiktor-Jedrzejczak W, Sanchez JF, Schaap N, Isaksson C, Lenhoff S, Browne P, Scheid C, Wilson KMO, Yakoub-Agha I, Muñiz SG, Schönland S, Morris C, Garderet L, Kröger N (2018) Incidence of second primary malignancies after autologous transplantation for multiple myeloma in the era of novel agents. Biol Blood Marrow Transplant 24:930–936. https://doi.org/10.1016/j.bbmt.2018.01.006

    Article  PubMed  Google Scholar 

  41. Razavi P, Rand KA, Cozen W, Chanan-Khan A, Usmani S, Ailawadhi S (2013) Patterns of second primary malignancy risk in multiple myeloma patients before and after the introduction of novel therapeutics. Blood Cancer J 3:e121. https://doi.org/10.1038/bcj.2013.19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Jonsdottir G, Lund SH, Bjorkholm M et al (2017) The impact of prior malignancies on second malignancies and survival in MM patients: a population-based study. Blood Adv 1:2392–2398. https://doi.org/10.1182/bloodadvances.2017007930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hasskarl J, Ihorst G, De Pasquale D et al (2011) Association of multiple myeloma with different neoplasms: systematic analysis in consecutive patients with myeloma. Leuk Lymphoma 52:247–259. https://doi.org/10.3109/10428194.2010.529207

    Article  PubMed  Google Scholar 

  44. Jones JR, Cairns DA, Gregory WM, Collett C, Pawlyn C, Sigsworth R, Striha A, Henderson R, Kaiser MF, Jenner M, Cook G, Russell NH, Williams C, Pratt G, Kishore B, Lindsay J, Drayson MT, Davies FE, Boyd KD, Owen RG, Jackson GH, Morgan GJ (2016) Second malignancies in the context of lenalidomide treatment: an analysis of 2732 myeloma patients enrolled to the Myeloma XI trial. Blood Cancer J 6:e506. https://doi.org/10.1038/bcj.2016.114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Knudsen LM, Hjorth M, Hippe E (2000) Renal failure in multiple myeloma: reversibility and impact on the prognosis. Nordic Myeloma Study Group. Eur J Haematol 65:175–181

    Article  CAS  PubMed  Google Scholar 

  46. Kistler KD, Kalman J, Sahni G et al (2017) Incidence and risk of cardiac events in patients with previously treated multiple myeloma versus matched patients without multiple myeloma: an observational, retrospective, cohort study. Clin Lymphoma Myeloma Leuk 17:89–96.e3. https://doi.org/10.1016/j.clml.2016.11.009

    Article  PubMed  Google Scholar 

  47. Kleber M, Ihorst G, Terhorst M, Koch B, Deschler B, Wäsch R, Engelhardt M (2011) Comorbidity as a prognostic variable in multiple myeloma: comparative evaluation of common comorbidity scores and use of a novel MM-comorbidity score. Blood Cancer J 1:e35. https://doi.org/10.1038/bcj.2011.34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kleber M, Ihorst G, Gross B et al (2013) Validation of the Freiburg Comorbidity Index in 466 multiple myeloma patients and combination with the international staging system are highly predictive for outcome. Clin Lymphoma Myeloma Leuk 13:541–551. https://doi.org/10.1016/j.clml.2013.03.013

    Article  PubMed  Google Scholar 

  49. Desikan KR, Dhodapkar MV, Hough A, Waldron T, Jagannath S, Siegel D, Barlogie B, Tricot G (1997) Incidence and impact of light chain associated (AL) amyloidosis on the prognosis of patients with multiple myeloma treated with autologous transplantation. Leuk Lymphoma 27:315–319. https://doi.org/10.3109/10428199709059685

    Article  CAS  PubMed  Google Scholar 

  50. Vela-Ojeda J, Garcia-Ruiz Esparza MA, Padilla-Gonzalez Y et al (2009) Multiple myeloma-associated amyloidosis is an independent high-risk prognostic factor. Ann Hematol 88:59–66. https://doi.org/10.1007/s00277-008-0554-0

    Article  CAS  PubMed  Google Scholar 

  51. Petruzziello F, Zeppa P, Catalano L, Cozzolino I, Gargiulo G, Musto P, D’Auria F, Liso V, Rizzi R, Caruso N, Califano C, Piro E, Musso M, Bonanno V, Pia Falcone A, Tafuto S, di Raimondo F, de Laurentiis M, Pane F, Palombini L, Rotoli B (2010) Amyloid in bone marrow smears of patients affected by multiple myeloma. Ann Hematol 89:469–474. https://doi.org/10.1007/s00277-009-0857-9

    Article  CAS  PubMed  Google Scholar 

  52. Siragusa S, Morice W, Gertz MA, Kyle RA, Greipp PR, Lust JA, Witzig TE, Lacy MQ, Zeldenrust SR, Rajkumar SV, Russell SJ, Hayman SR, Buadi F, Kumar SK, Dingli D, Dispenzieri A (2011) Asymptomatic immunoglobulin light chain amyloidosis (AL) at the time of diagnostic bone marrow biopsy in newly diagnosed patients with multiple myeloma and smoldering myeloma. A series of 144 cases and a review of the literature. Ann Hematol 90:101–106. https://doi.org/10.1007/s00277-010-1028-8

    Article  CAS  PubMed  Google Scholar 

  53. Chakraborty R, Gertz MA, Dispenzieri A, Gonsalves WI, Zeldenrust SR, Russell SJ, Go RS, Kapoor P, Rajkumar VS, Hayman SR, Hwa YL, Lacy MQ, Kyle RA, Leung N, Kumar SK (2017) Natural history of amyloidosis isolated to fat and bone marrow aspirate. Br J Haematol 179:170–172. https://doi.org/10.1111/bjh.14205

    Article  PubMed  Google Scholar 

  54. Ivanyi B (1990) Frequency of light chain deposition nephropathy relative to renal amyloidosis and Bence Jones cast nephropathy in a necropsy study of patients with myeloma. Arch Pathol Lab Med 114:986–987

    CAS  PubMed  Google Scholar 

  55. Kapadia SB (1980) Multiple myeloma: a clinicopathologic study of 62 consecutively autopsied cases. Medicine (Baltimore) 59:380–392

    Article  CAS  Google Scholar 

  56. Kyle RA (1975) Multiple myeloma: review of 869 cases. Mayo Clin Proc 50:29–40

    CAS  PubMed  Google Scholar 

Download references

Funding

This study was funded by the budget of the Südtiroler Sanitätsbetrieb.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dominic Fong.

Ethics declarations

Ethical approval

All procedures performed in this study that involved human participants were in accordance with the ethical standards of the institutional committee, national research committee, and the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The Ethics Committee of the “Südtiroler Sanitätsbetrieb” approved this study by the protocol number 81-2018.

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 16 kb)

ESM 2

(DOCX 22 kb)

ESM 3

(PNG 53 kb)

High resolution image (EPS 15 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mair, M., Straka, C., Buratti, T. et al. Clinical outcomes and prognostic factors in patients with multiple myeloma in South Tyrol: a retrospective single-center analysis. Ann Hematol 99, 1031–1040 (2020). https://doi.org/10.1007/s00277-020-03969-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-020-03969-9

Keywords

Navigation