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Published in: Annals of Hematology 6/2019

01-06-2019 | Multiple Myeloma | Original Article

Pulmonary function abnormalities are common in patients with multiple myeloma and are independently associated with worse outcome

Authors: Georgia Trakada, Efstathios Kastritis, Maria Gavriatopoulou, Lemonia Velentza, Despina Fotiou, Dimitrios C. Ziogas, Ioannis Panagiotidis, Evangelos Eleutherakis-Papaiakovou, Maria Roussou, Magdalini Migkou, Nikolaos Kanellias, Ioannis Ntanasis-Stathopoulos, Anastasios Kallianos, Evangelos Terpos, Meletios A. Dimopoulos

Published in: Annals of Hematology | Issue 6/2019

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Abstract

Pre-existing pulmonary disease may affect treatment choices, toxicity, and survival of patients with multiple myeloma (MM). However, data on the prognostic value of pulmonary function tests (PFTs) in myeloma patients’ outcome, at the time of initial assessment of newly diagnosed patients, are scarce. Here, we prospectively performed PFTs in 121 newly diagnosed MM patients, before initiation of treatment, and we evaluated possible associations of lung function with their outcomes. Fifty-four patients (44.63%) had either obstructive or restrictive pulmonary function defects, even among those not reporting a history of lung disease. The survival was significantly worse in those with obstructive pulmonary defect (median OS 32.8 months) vs. those with restrictive (median OS 52.5 months) or normal lung function (median not reached, 3-year survival 76%) (p = 0.013), independently of other myeloma-related factors. Forced vital capacity (FVC) (lt) (p = 0.012), forced expiratory volume in 1 s (FEV1) (lt) (p = 0.018), peak expiratory flow (PEF) (lt/min) (p = 0.008), carbon monoxide diffusion capacity (DLCO) (p = 0.012), and expiratory/inspiratory pressures (Pe) (kPa) (p = 0.032)/(Pi) (kPa) (p = 0.023) were significantly associated with OS. Myeloma-related factors associated with survival included ISS stage (p = 0.008), hypercalcemia (p = 0.064), and high-risk cytogenetics (p = 0.004). In the multivariate analysis, only the presence of high-risk cytogenetics and presence of either or both PEF and DLCO < 65% of predicted were independent prognostic factors. We conclude that PEF and DLCO could be useful in the initial assessment of newly diagnosed MM patients as significant predictors of survival. Further research is needed to evaluate if respiratory screening should be included in the routine initial evaluation of myeloma patients, despite the presence or absence of respiratory symptoms or abnormal clinical respiratory examination.
Literature
1.
go back to reference Dimopoulos M, Kyle R, Fermand JP, Rajkumar SV, San Miguel J, Chanan-Khan A, Ludwig H, Joshua D, Mehta J, Gertz M, Avet-Loiseau H, Beksac M, Anderson KC, Moreau P, Singhal S, Goldschmidt H, Boccadoro M, Kumar S, Giralt S, Munshi NC, Jagannath S, on behalf of the International Myeloma Workshop Consensus Panel 3 (2011) Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood 117:4701–4705CrossRefPubMed Dimopoulos M, Kyle R, Fermand JP, Rajkumar SV, San Miguel J, Chanan-Khan A, Ludwig H, Joshua D, Mehta J, Gertz M, Avet-Loiseau H, Beksac M, Anderson KC, Moreau P, Singhal S, Goldschmidt H, Boccadoro M, Kumar S, Giralt S, Munshi NC, Jagannath S, on behalf of the International Myeloma Workshop Consensus Panel 3 (2011) Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood 117:4701–4705CrossRefPubMed
3.
go back to reference Kumar S (2012) Risk of early death in multiple myeloma. Clin Adv Hematol Oncol 10:172–174PubMed Kumar S (2012) Risk of early death in multiple myeloma. Clin Adv Hematol Oncol 10:172–174PubMed
4.
go back to reference 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 28:1122–1128CrossRefPubMed 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 28:1122–1128CrossRefPubMed
5.
go back to reference 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 NWCJ, Einsele H, Blade J, Durie BGM, 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 127:2955–2962CrossRefPubMedPubMedCentral 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 NWCJ, Einsele H, Blade J, Durie BGM, 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 127:2955–2962CrossRefPubMedPubMedCentral
6.
go back to reference Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, Richardson P, Caltagirone S, Lahuerta JJ, Facon T, Bringhen S, Gay F, Attal M, Passera R, Spencer A, Offidani M, Kumar S, Musto P, Lonial S, Petrucci MT, Orlowski RZ, Zamagni E, Morgan G, Dimopoulos MA, Durie BGM, Anderson KC, Sonneveld P, San Miguel J, Cavo M, Rajkumar SV, Moreau P (2015) Revised international staging system for multiple myeloma: a report from International Myeloma Working Group. J Clin Oncol 33:2863–2869CrossRefPubMedPubMedCentral Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, Richardson P, Caltagirone S, Lahuerta JJ, Facon T, Bringhen S, Gay F, Attal M, Passera R, Spencer A, Offidani M, Kumar S, Musto P, Lonial S, Petrucci MT, Orlowski RZ, Zamagni E, Morgan G, Dimopoulos MA, Durie BGM, Anderson KC, Sonneveld P, San Miguel J, Cavo M, Rajkumar SV, Moreau P (2015) Revised international staging system for multiple myeloma: a report from International Myeloma Working Group. J Clin Oncol 33:2863–2869CrossRefPubMedPubMedCentral
7.
go back to reference Kastritis E, Terpos E, Roussou M, Gavriatopoulou M, Migkou M, Eleutherakis-Papaiakovou E, Fotiou D, Ziogas D, Panagiotidis I, Kafantari E, Giannouli S, Zomas A, Konstantopoulos K, Dimopoulos MA (2017) Evaluation of the Revised International Staging System in an independent cohort of unselected patients with multiple myeloma. Haematologica 102:593–599CrossRefPubMedPubMedCentral Kastritis E, Terpos E, Roussou M, Gavriatopoulou M, Migkou M, Eleutherakis-Papaiakovou E, Fotiou D, Ziogas D, Panagiotidis I, Kafantari E, Giannouli S, Zomas A, Konstantopoulos K, Dimopoulos MA (2017) Evaluation of the Revised International Staging System in an independent cohort of unselected patients with multiple myeloma. Haematologica 102:593–599CrossRefPubMedPubMedCentral
8.
go back to reference Greipp PR, San Miguel J, Durie BG et al (2005) International staging system for multiple myeloma. J Clin Oncol 23:3412–3420CrossRefPubMed Greipp PR, San Miguel J, Durie BG et al (2005) International staging system for multiple myeloma. J Clin Oncol 23:3412–3420CrossRefPubMed
9.
go back to reference Crawford SW, Fisher L (1992) Predictive value of pulmonary function tests before marrow transplantation. Chest 101:1257–1264CrossRefPubMed Crawford SW, Fisher L (1992) Predictive value of pulmonary function tests before marrow transplantation. Chest 101:1257–1264CrossRefPubMed
10.
go back to reference Mohammadi M, Cao Y, Glimelius I, Bottai M, Eloranta S, Smedby KE (2015) The impact of comorbid disease history on all-cause and cancer-specific mortality in myeloid leukemia and myeloma—a Swedish population-based study. BMC Cancer 15:850CrossRefPubMedPubMedCentral Mohammadi M, Cao Y, Glimelius I, Bottai M, Eloranta S, Smedby KE (2015) The impact of comorbid disease history on all-cause and cancer-specific mortality in myeloid leukemia and myeloma—a Swedish population-based study. BMC Cancer 15:850CrossRefPubMedPubMedCentral
11.
go back to reference 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 13:541–551CrossRefPubMed 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 13:541–551CrossRefPubMed
12.
go back to reference Miller MR, Crapo R, Hankinson J et al (2005) General considerations for lung function testing. Eur Respir J 26:153–161CrossRefPubMed Miller MR, Crapo R, Hankinson J et al (2005) General considerations for lung function testing. Eur Respir J 26:153–161CrossRefPubMed
13.
go back to reference Graham BL, Brusasco V, Burgos F et al (2017) ERS/ATS standards for single-breath carbon monoxide uptake in the lung. Eur Respir J 2017:49 Graham BL, Brusasco V, Burgos F et al (2017) ERS/ATS standards for single-breath carbon monoxide uptake in the lung. Eur Respir J 2017:49
14.
go back to reference Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten C, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J, ATS/ERS Task Force (2005) Standardisation of spirometry. Eur Respir J 26:319–338CrossRefPubMed Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten C, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J, ATS/ERS Task Force (2005) Standardisation of spirometry. Eur Respir J 26:319–338CrossRefPubMed
15.
go back to reference Wanger J, Clausen JL, Coates A, Pedersen OF, Brusasco V, Burgos F, Casaburi R, Crapo R, Enright P, van der Grinten CPM, Gustafsson P, Hankinson J, Jensen R, Johnson D, MacIntyre N, McKay R, Miller MR, Navajas D, Pellegrino R, Viegi G (2005) Standardisation of the measurement of lung volumes. Eur Respir J 26:511–522CrossRefPubMed Wanger J, Clausen JL, Coates A, Pedersen OF, Brusasco V, Burgos F, Casaburi R, Crapo R, Enright P, van der Grinten CPM, Gustafsson P, Hankinson J, Jensen R, Johnson D, MacIntyre N, McKay R, Miller MR, Navajas D, Pellegrino R, Viegi G (2005) Standardisation of the measurement of lung volumes. Eur Respir J 26:511–522CrossRefPubMed
16.
go back to reference Macintyre N, Crapo RO, Viegi G, Johnson DC, van der Grinten C, Brusasco V, Burgos F, Casaburi R, Coates A, Enright P, Gustafsson P, Hankinson J, Jensen R, McKay R, Miller MR, Navajas D, Pedersen OF, Pellegrino R, Wanger J (2005) Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J 26:720–735CrossRefPubMed Macintyre N, Crapo RO, Viegi G, Johnson DC, van der Grinten C, Brusasco V, Burgos F, Casaburi R, Coates A, Enright P, Gustafsson P, Hankinson J, Jensen R, McKay R, Miller MR, Navajas D, Pedersen OF, Pellegrino R, Wanger J (2005) Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J 26:720–735CrossRefPubMed
17.
go back to reference Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, Coates A, van der Grinten C, Gustafsson P, Hankinson J, Jensen R, Johnson DC, MacIntyre N, McKay R, Miller MR, Navajas D, Pedersen OF, Wanger J (2005) Interpretative strategies for lung function tests. Eur Respir J 26:948–968CrossRefPubMed Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, Coates A, van der Grinten C, Gustafsson P, Hankinson J, Jensen R, Johnson DC, MacIntyre N, McKay R, Miller MR, Navajas D, Pedersen OF, Wanger J (2005) Interpretative strategies for lung function tests. Eur Respir J 26:948–968CrossRefPubMed
18.
go back to reference Crapo RO, Forster RE 2nd (1989) Carbon monoxide diffusing capacity. Clin Chest Med 10:187–198PubMed Crapo RO, Forster RE 2nd (1989) Carbon monoxide diffusing capacity. Clin Chest Med 10:187–198PubMed
19.
go back to reference Cooper BG (2011) Republished review: an update on contraindications for lung function testing. Postgrad Med J 87:724–733CrossRefPubMed Cooper BG (2011) Republished review: an update on contraindications for lung function testing. Postgrad Med J 87:724–733CrossRefPubMed
20.
go back to reference Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, Chen R, Decramer M, Fabbri LM, Frith P, Halpin DMG, López Varela MV, Nishimura M, Roche N, Rodriguez-Roisin R, Sin DD, Singh D, Stockley R, Vestbo J, Wedzicha JA, Agusti A (2017) Global strategy for the diagnosis, management and prevention of chronic obstructive lung disease 2017 report: GOLD executive summary. Respirology 22:575–601CrossRefPubMed Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, Chen R, Decramer M, Fabbri LM, Frith P, Halpin DMG, López Varela MV, Nishimura M, Roche N, Rodriguez-Roisin R, Sin DD, Singh D, Stockley R, Vestbo J, Wedzicha JA, Agusti A (2017) Global strategy for the diagnosis, management and prevention of chronic obstructive lung disease 2017 report: GOLD executive summary. Respirology 22:575–601CrossRefPubMed
23.
go back to reference Moreau P, San Miguel J, Sonneveld P, Mateos MV, Zamagni E, Avet-Loiseau H, Hajek R, Dimopoulos MA, Ludwig H, Einsele H, Zweegman S, Facon T, Cavo M, Terpos E, Goldschmidt H, Attal M, Buske C, on behalf of the ESMO Guidelines Committee (2017) Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 28:iv52–iv61CrossRefPubMed Moreau P, San Miguel J, Sonneveld P, Mateos MV, Zamagni E, Avet-Loiseau H, Hajek R, Dimopoulos MA, Ludwig H, Einsele H, Zweegman S, Facon T, Cavo M, Terpos E, Goldschmidt H, Attal M, Buske C, on behalf of the ESMO Guidelines Committee (2017) Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 28:iv52–iv61CrossRefPubMed
24.
go back to reference Forum of International Respiratory Societies (2017) The global impact of respiratory disease – second edition. Sheffield, European Respiratory Society. Available from: https://www.firsnet.org Forum of International Respiratory Societies (2017) The global impact of respiratory disease – second edition. Sheffield, European Respiratory Society. Available from: https://​www.​firsnet.​org
25.
go back to reference Martinez CH, Mannino DM, Jaimes FA, Curtis JL, Han MLK, Hansel NN, Diaz AA (2015) Undiagnosed obstructive lung disease in the United States. Associated factors and long-term mortality. Ann Am Thorac Soc 12:1788–1795CrossRefPubMedPubMedCentral Martinez CH, Mannino DM, Jaimes FA, Curtis JL, Han MLK, Hansel NN, Diaz AA (2015) Undiagnosed obstructive lung disease in the United States. Associated factors and long-term mortality. Ann Am Thorac Soc 12:1788–1795CrossRefPubMedPubMedCentral
26.
go back to reference Kannel WB, Lew EA, Hubert HB, Castelli WP (1980) The value of measuring vital capacity for prognostic purposes. Trans Assoc Life Insur Med Dir Am 64:66–83PubMed Kannel WB, Lew EA, Hubert HB, Castelli WP (1980) The value of measuring vital capacity for prognostic purposes. Trans Assoc Life Insur Med Dir Am 64:66–83PubMed
27.
go back to reference Coultas DB, Zumwalt RE, Black WC, Sobonya RE (1994) The epidemiology of interstitial lung diseases. Am J Respir Crit Care Med 150:967–972CrossRefPubMed Coultas DB, Zumwalt RE, Black WC, Sobonya RE (1994) The epidemiology of interstitial lung diseases. Am J Respir Crit Care Med 150:967–972CrossRefPubMed
28.
go back to reference Augustson BM, Begum G, Dunn JA, Barth NJ, Davies F, Morgan G, Behrens J, Smith A, Child JA, Drayson MT (2005) Early mortality after diagnosis of multiple myeloma: analysis of patients entered onto the United Kingdom Medical Research Council trials between 1980 and 2002—Medical Research Council Adult Leukaemia Working Party. J Clin Oncol 23:9219–9226CrossRefPubMed Augustson BM, Begum G, Dunn JA, Barth NJ, Davies F, Morgan G, Behrens J, Smith A, Child JA, Drayson MT (2005) Early mortality after diagnosis of multiple myeloma: analysis of patients entered onto the United Kingdom Medical Research Council trials between 1980 and 2002—Medical Research Council Adult Leukaemia Working Party. J Clin Oncol 23:9219–9226CrossRefPubMed
29.
go back to reference Zagouri F, Roussou M, Kastritis E, Koureas A, Tsokou E, Migkou M, Gavriatopoulou M, Nikitas N, Gkotzamanidou M, Terpos E, Dimopoulos MA (2011) Lenalidomide-associated pneumonitis in patients with plasma cell dyscrasias. Am J Hematol 86:882–884CrossRefPubMed Zagouri F, Roussou M, Kastritis E, Koureas A, Tsokou E, Migkou M, Gavriatopoulou M, Nikitas N, Gkotzamanidou M, Terpos E, Dimopoulos MA (2011) Lenalidomide-associated pneumonitis in patients with plasma cell dyscrasias. Am J Hematol 86:882–884CrossRefPubMed
30.
go back to reference Engelhardt M, Domm AS, 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 102:910–921CrossRefPubMedPubMedCentral Engelhardt M, Domm AS, 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 102:910–921CrossRefPubMedPubMedCentral
31.
go back to reference Tockman MS, Comstock GW (1989) Respiratory risk factors and mortality: longitudinal studies in Washington County, Maryland. Am Rev Respir Dis 140:S56–S63CrossRefPubMed Tockman MS, Comstock GW (1989) Respiratory risk factors and mortality: longitudinal studies in Washington County, Maryland. Am Rev Respir Dis 140:S56–S63CrossRefPubMed
32.
go back to reference Neas LM, Schwartz J (1998) Pulmonary function levels as predictors of mortality in a national sample of US adults. Am J Epidemiol 147:1011–1018CrossRefPubMed Neas LM, Schwartz J (1998) Pulmonary function levels as predictors of mortality in a national sample of US adults. Am J Epidemiol 147:1011–1018CrossRefPubMed
33.
go back to reference Kannel WB, Hubert H, Lew EA (1983) Vital capacity as a predictor of cardiovascular disease: the Framingham study. Am Heart J 105:311–315CrossRefPubMed Kannel WB, Hubert H, Lew EA (1983) Vital capacity as a predictor of cardiovascular disease: the Framingham study. Am Heart J 105:311–315CrossRefPubMed
Metadata
Title
Pulmonary function abnormalities are common in patients with multiple myeloma and are independently associated with worse outcome
Authors
Georgia Trakada
Efstathios Kastritis
Maria Gavriatopoulou
Lemonia Velentza
Despina Fotiou
Dimitrios C. Ziogas
Ioannis Panagiotidis
Evangelos Eleutherakis-Papaiakovou
Maria Roussou
Magdalini Migkou
Nikolaos Kanellias
Ioannis Ntanasis-Stathopoulos
Anastasios Kallianos
Evangelos Terpos
Meletios A. Dimopoulos
Publication date
01-06-2019
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 6/2019
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-019-03641-x

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