Abstract
Multiple myeloma (MM) is a heterogeneous disease. Evaluation of prognostic factors and risk stratification at diagnosis is necessary to compare outcome. Attempts have been made to apply a comorbidity score in the clinical sitting, but a standardized general approach is still lacking.
We hypothesized that a comprehensive examination of every associated disease in a large cohort of patients could better highlight the prognostic impact of comorbidity in MM.
All consecutive patients diagnosed in our institution, from 1993 to 2013, with symptomatic MM according to IMWG criteria were included in our population-based MM registry. Patients with plasma cell leukemia or with palliative management were excluded. Clinical variables analyzed were: age, sex, Durie-Salmon, International Scoring System (ISS), percentage of plasma cell in bone marrow by morphology (PC), serum creatinine (Cr) and estimated glomerular filtration rate according with Modification of Diet in Renal Disease (eGFR-MDRD). The following comorbodities were analysed: hypertension (HTA), diabetes (DM), obesity (OB) (body mass index > 30 Kg/m2), hyperlipaemia (HL), prior malignancy (PM), hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), peptic ulcer (PU), thromboembolism (TE), renal transplant (RT), splenectomy (S), cutaneous disease (CD), amyloidosis (AM), heart disease (HD) (arrhythmia, congestive heart failure, coronary artery disease, other), lung disease (LD) (chronic obstructive pulmonary disease, asthma, other), liver disease (HE) (cirrhosis, non-alcoholic fatty liver disease, other), neurological disorder (ND), psychiatric disorder (PD) and rheumatologic disorder (RD). Kaplan-Meier method was used to estimate OS curves. Cox regression was used to determine the prognostic impact of each comorbidity in a univariate and multivariate model.
311 patients were eligible. Median age was 66 years (12-91), 148 men (47.6 %) and 163 women. Percentage of comorbidities was: HTA 45; OB 32.5; DM 20.4; HD 20.4; LD 15.2; PU 10; HL 9.7; ND 8; PM 7.8; PD 6.5; HBV 3.9; HE 3.9; TE 3.6; RD 3,5; AM 2.3; HCV 1.9; CD 1.6; S 1; RT 0.6; HIV 0.3. 63 patients (20.4 %) showed no comorbidities. Univariate analysis (table 1) demonstrated that AM (P=0.022), HCV (0.038), HIV (0.022), PD (0.015) and ND (0.05) were significantly associated with shorter OS. The variables associated with mortality in the multivariate analysis were age (p=0.002), ISS (III vs I: p=0.01), PC (p=0.05) and Cr (p=0.02). Results will be validated in another MM series and presented during the meeting.
| Comorbidity . | Definition . | N (%) . | Median OS . | HR (95% CI) . | P-value . |
|---|---|---|---|---|---|
| Hypertension | -No -Yes | 170 139 (45) | 31 34 | 1,009 (0,764-1,332) | 0,951 |
| Diabetes | -No -Yes | 246 63 (20,4) | 32 42 | 1,111 (0,794-1,554) | 0,540 |
| Obesity | -No -Yes | 164 79 (32,5) | 49 36 | 1,226 (0,861-1,745) | 0,258 |
| Hyperlipaemia | -No -Yes | 279 30 (9,7) | 32 47 | 0,723 (0,427-1,223) | 0,227 |
| Prior malignancy | -No -Yes | 285 24 (7,8) | 34 29 | 1,172 (0,712-1,928) | 0,533 |
| HBV | -No -Yes | 297 12 (3,9) | 32 NR | 0,365 (0,117-1,142) | 0,083 |
| HCV | -No -Yes | 303 6 (1,9) | 33 7 | 2,575 (1.053-6,294) | 0.038 |
| HIV | -No -Yes | 308 1 (0,3) | 33 1 | 10,290 (1,402-75,542) | 0,022 |
| Peptic ulcer | -No -Yes | 278 31 (10) | 32 40 | 0,971 (0,623-1,512) | 0,895 |
| Thromboembolism | -No -Yes | 298 11 (3,6) | 33 33 | 1,777 (0,936-3,372) | 0,079 |
| Renal transplant | -No -Yes | 307 2 (0,6) | 33 5 | 2,075 (0,288-14,934) | 0,468 |
| Splenectomy | -No -Yes | 306 3 (1) | 33 29 | 1,559 0,386-6,302) | 0,533 |
| Cutaneous disease | -No -Yes | 304 5 (1,6) | 33 67 | 0,598 (0,148-2,410) | 0,470 |
| Amyloidosis | -No -Yes | 303 7 (2,3) | 34 13 | 2,428 (1,139-5,176) | 0,022 |
| Heart disease | -No -Yes -Arrhythmia -CHF -CAD -Other | 247 63 (20,4) 20 21 17 5 | 33 32 32 42 29 25 | 1,245 (0,898-1,727) | 0,189 |
| Lung disease | -No -Yes -COPD -Astma -Other | 262 47 (15,2) 27 146 | 32 33 31 52 33 | 1,075 (0,740-1,562) | 0,702 |
| Liver disease | -No -Yes -Cirrhosis -NAFLD -Other | 297 12 (3,9) 2 6 4 | 33 10 1 8 16 | 1,341 (0,709-2,536) | 0,367 |
| Neurological disorder | -No -Yes | 286 25 (8) | 34 24 | 1,610 (0,989-2,621) | 0,056 |
| Psychiatric disorder | -No -Yes | 289 20 (6,5) | 33 15 | 1,894 (1,130-3,176) | 0,015 |
| Rheumatologic disorder | -No -Yes | 300 11 (3,5) | 33 88 | 0,702 (0,311-1,584) | 0,394 |
| Comorbidity . | Definition . | N (%) . | Median OS . | HR (95% CI) . | P-value . |
|---|---|---|---|---|---|
| Hypertension | -No -Yes | 170 139 (45) | 31 34 | 1,009 (0,764-1,332) | 0,951 |
| Diabetes | -No -Yes | 246 63 (20,4) | 32 42 | 1,111 (0,794-1,554) | 0,540 |
| Obesity | -No -Yes | 164 79 (32,5) | 49 36 | 1,226 (0,861-1,745) | 0,258 |
| Hyperlipaemia | -No -Yes | 279 30 (9,7) | 32 47 | 0,723 (0,427-1,223) | 0,227 |
| Prior malignancy | -No -Yes | 285 24 (7,8) | 34 29 | 1,172 (0,712-1,928) | 0,533 |
| HBV | -No -Yes | 297 12 (3,9) | 32 NR | 0,365 (0,117-1,142) | 0,083 |
| HCV | -No -Yes | 303 6 (1,9) | 33 7 | 2,575 (1.053-6,294) | 0.038 |
| HIV | -No -Yes | 308 1 (0,3) | 33 1 | 10,290 (1,402-75,542) | 0,022 |
| Peptic ulcer | -No -Yes | 278 31 (10) | 32 40 | 0,971 (0,623-1,512) | 0,895 |
| Thromboembolism | -No -Yes | 298 11 (3,6) | 33 33 | 1,777 (0,936-3,372) | 0,079 |
| Renal transplant | -No -Yes | 307 2 (0,6) | 33 5 | 2,075 (0,288-14,934) | 0,468 |
| Splenectomy | -No -Yes | 306 3 (1) | 33 29 | 1,559 0,386-6,302) | 0,533 |
| Cutaneous disease | -No -Yes | 304 5 (1,6) | 33 67 | 0,598 (0,148-2,410) | 0,470 |
| Amyloidosis | -No -Yes | 303 7 (2,3) | 34 13 | 2,428 (1,139-5,176) | 0,022 |
| Heart disease | -No -Yes -Arrhythmia -CHF -CAD -Other | 247 63 (20,4) 20 21 17 5 | 33 32 32 42 29 25 | 1,245 (0,898-1,727) | 0,189 |
| Lung disease | -No -Yes -COPD -Astma -Other | 262 47 (15,2) 27 146 | 32 33 31 52 33 | 1,075 (0,740-1,562) | 0,702 |
| Liver disease | -No -Yes -Cirrhosis -NAFLD -Other | 297 12 (3,9) 2 6 4 | 33 10 1 8 16 | 1,341 (0,709-2,536) | 0,367 |
| Neurological disorder | -No -Yes | 286 25 (8) | 34 24 | 1,610 (0,989-2,621) | 0,056 |
| Psychiatric disorder | -No -Yes | 289 20 (6,5) | 33 15 | 1,894 (1,130-3,176) | 0,015 |
| Rheumatologic disorder | -No -Yes | 300 11 (3,5) | 33 88 | 0,702 (0,311-1,584) | 0,394 |
The overall prognosis of MM depends on a variety of host and disease-related characteristics. We confirm age, ISS, PC and Cr as robust and independent prognostic factors. Adjusting for these factors, no isolated comorbidity reach statistical significance; however, comorbidity seems to have a role in MM prognosis. More studies are warranted to define the prognostic impact of comorbidities in MM.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
