Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc
Journal website https://www.thejh.org

Short Communication

Volume 13, Number 5, October 2024, pages 207-215

Siltuximab in Idiopathic Multicentric Castleman Disease: Real-World Experience

Figure

Figure 1.
Figure 1. Kaplan-Meier curve of overall survival. CI: confidence interval; NA: not available.

Tables

Table 1. Baseline Characteristics and Details of Treatment
 
VariableCohortP-valuea
Overall (N = 48)Greece (n = 28)Romania (n = 20)
aPearson’s Chi-squared test; Wilcoxon rank sum exact test; Fisher’s exact test. CHOP: cyclophosphamide, doxorubicin, vincristine, prednisolone; CFA: complete Freund’s adjuvant; CVP: cyclophosphamide, vincristine, prednisolone; DEXA: dexamethasone; DOXO: doxorubicin; HHV-8: human herpesvirus-8; HIV: human immunodeficiency virus; R: rituximab; R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone; R-CVP: rituximab, cyclophosphamide, vincristine, prednisolone; SD: standard deviation.
Sex, n/N (%)0.082
  Male33/48 (68.8)22/28 (78.6)11/20 (55.0)
  Female15/48 (31.3)6/28 (21.4)9/20 (45.0)
Age (years), mean (SD)65 (19.0)74 (18.0)54 (14.0)< 0.001
Fever, n/N (%)< 0.001
  Yes19/48 (39.6)17/28 (60.7)2/20 (10.0)
  No27/48 (56.3)9/28 (32.1)18/20 (90.0)
  Unknown2/48 (4.2)0/20 (0.0)2/28 (7.1)
Night sweats, n/N (%)0.47
  Yes19/48 (39.6)12/28 (42.9)7/20 (35.0)
  No27/48 (56.3)14/28 (50.0)13/20 (65.0)
  Unknown2/48 (4.2)0/20 (0.0)2/28 (7.1)
Weight loss, n/N (%)0.27
  Yes30/48 (62.5)19/28 (67.9)11/20 (55.0)
  No16/48 (33.3)7/28 (25.0)9/20 (45.0)
  Unknown2/48 (4.2)2/28 (7.1)0/20 (0.0)
Asthenia, n/N (%)0.67
  Yes33/48 (68.8)19/28 (68.9)14/20 (70.0)
  No13/48 (27.1)7/28 (25.0)6/20 (30.0)
  Unknown2/48 (4.2)2/28 (7.1)0/20 (0.0)
Threatened end organ function: bowel ischemia due to bowel obstruction from enlarged node, n/N (%)0.15
  Yes2/48 (4.2)0/28 (0.0)2/20 (10.0)
  No44/48 (91.7)26/28 (92.9)18/20 (90.0)
  Unknown2/48 (4.2)2/28 (7.1)0/20 (0.0)
Threatened end organ function: renal failure/impairment due to ureteral obstruction by enlarged node, n/N (%)0.63
  Yes3/48 (6.2)2/28 (7.1)1/20 (5.0)
  No43/48 (89.6)24/28 (85.7)19/20 (95.0)
  Unknown2/48 (4.2)2/28 (7.1)0/20 (0.0)
Threatened end organ function: liver impairment, n/N (%)0.50
  Yes7/48 (14.6)3/28 (10.7)4/20 (20.0)
  No39/48 (81.5)23/28 (82.1)16/20 (80.0)
  Unknown2/48 (4.2)2/28 (7.1)0/20 (0.0)
Single mass, n/N (%)0.42
  Yes2/48 (4.2)0/20 (0.0)2/28 (7.1)
  No44/48 (91.7)20/20 (100.0)24/28 (85.7)
  Unknown2/48 (4.2)0/20 (0.0)2/28 (7.1)
Two or more masses, n/N (%)0.17
  Yes40/48 (83.3)21/28 (75.0)19/20 (95.0)
  No6/48 (12.5)5/28 (17.9)1/20 (5.0)
  Unknown2/48 (4.2)2/28 (7.1)0/20 (0.0)
Splenomegaly, n/N (%)29/48 (60.4)9/20 (45.0)20/28 (71.4)0.065
Method for splenomegaly assessment n/N, (%)< 0.001
  Clinician6/48 (12.5)0/28 (0.0)6/20 (30.0)
  Radiology2/48 (4.2)0/28 (0.0)2/20 (10.0)
  Clinician and radiology37/48 (77.1)26/28 (92.9)11/20 (55.0)
  Unknown3/48 (6.2)2/28 (7.1)1/20 (5.0)
Pleural or peritoneal serous effusion (irrespective of cell content), n/N (%)17/48 (35.4)12/28 (42.8)5/20 (25.0)0.20
Anemia, n/N (%)27/48 (56.3)21/28 (75.0)6/20 (30.0)0.002
Lymphopenia, n/N (%)12/48 (25.0)8/28 (28.6)4/20 (20.0)0.50
Transformation to aggressive lymphoma, n/N (%)0.073
  Yes4/48 (8.3)4/28 (14.3)0/20 (0.0)
  No43/48 (89.6)24/28 (85.7)19/20 (95.0)
  Unknown1/48 (2.1)0/28 (0.0)1/20 (5.0)
Malignancies, n/N (%)7/48 (14.6)5/28 (17.9)2/20 (10.0)0.68
Autoimmune diseases, n/N (%)5/48 (10.4)3/28 (10.7)2/20 (10.0)> 0.99
Cardiovascular diseases, n/N (%)21/48 (43.8)14/28 (50.0)7/20 (35.0)0.30
Diabetes, n/N (%)8/48 (16.7)7/28 (25.0)1/20 (5.0)0.12
HHV-8 infections, n/N (%)1/48 (2.1)1/28 (3.6)0/20 (0.0)> 0.99
HIV infections, n/N (%)2/48 (4.2)1/28 (3.6)1/20 (5.0)> 0.99
Hepatomegaly, n/N (%)0.27
  Yes24/48 (50.0)14/28 (50.0)10/20 (50.0)
  No22/48 (45.8)14/28 (50.0)8/20 (40.0)
  Unknown2/48 (4.2)0/28 (0.0)2/20 (10.0)
Gastric manifestation, n/N (%)4/48 (8.3)4/28 (14.3)0/20 (0.0)0.13
Thyroid manifestation, n/N (%)3/48 (6.2)3/28 (10.7)0/20 (0.0)0.26
Pancreas manifestation, n/N (%)1/48 (2.1)0/28 (0.0)1/20 (5.0)0.42
Hepatic manifestation, n/N (%)5/48 (10.4)2/28 (7.1)3/20 (15.0)0.64
Renal manifestation, n/N (%)4/48 (8.3)2/28 (7.1)2/20 (10.0)> 0.99
Pulmonary manifestation, n/N (%)16/48 (33)12/28 (42.9)4/20 (20.0)0.10
Radiation therapy, n/N (%)0.046
  Yes3/48 (6.2)1/28 (3.6)2/20 (10.0)
  No37/48 (77.1)25/28 (89.3)12/20 (60.0)
  Unknown8/48 (16.7)2/28 (7.1)6/20 (30.0)
Previous therapeutic strategies, n/N (%)0.030
  CFA-DEXA1/48 (2.1)0/28 (0.0)1/20 (5.0)
  CHOP1/48 (2.1)1/28 (3.6)0/20 (0.0)
  Corticosteroids4/48 (8.3)3/28 (10.7)1/20 (5.0)
  CVP1/48 (2.1)1/28 (3.6)0/20 (0.0)
  CVP, R-CHOP1/48 (2.1)1/28 (3.6)0/20 (0.0)
  CVP/Etoposide3/48 (6.2)0/28 (0.0)3/20 (15.0)
  Melphalan-Vc-methylprednisolone1/48 (2.1)1/28 (3.6)0/20 (0.0)
  None3/48 (6.2)3/28 (10.7)0/20 (0.0)
  R-CFA-DOXO-PREDNISON1/48 (2.1)0/28 (0.0)1/20 (5.0)
  R-CHOP11/48 (22.9)8/28 (28.6)3/20 (15.0)
  R-CHOP/etoposide1/48 (2.1)0/28 (0.0)1/20 (5.0)
  R-CVP5/48 (10.4)4/28 (14.3)1/20 (5.0)
  R-CVP + R maintenance1/48 (2.1)1/28 (3.6)0/20 (0.0)
  R-CVP/etoposide2/48 (4.2)0/28 (0.0)2/20 (10.0)
  Rituximab1/48 (2.1)1/28 (3.6)0/20 (0.0)
  Siltuximab10/48 (20.8)3/28 (10.7)7/20 (35.0)
  Tocilizumab1/48 (2.1)1/28 (3.6)0/20 (0.0)
Number of prior lines of treatment before siltuximab, n/N (%)0.006
  03/48 (6.2)3/28 (10.7)0/20 (0.0)
  136/48 (75.0)16/28 (57.1)20/20 (100.0)
  26/48 (12.5)6/28 (21.4)0/20 (0.0)
  32/48 (4.2)2/28 (7.1)0/20 (0.0)
  Unknown1/48 (2.1)1/28 (3.6)0/20 (0.0)
Number of siltuximab cycles, n/N (%)0.10
  01/48 (2.1)1/28 (3.6)0/20 (0.0)
  17/48 (14.6)5/28 (17.9)2/20 (10.0)
  22/48 (4.2)2/28 (7.1)0/20 (0.0)
  41/48 (2.1)1/28 (3.6)0/20 (0.0)
  611/48 (22.9)4/28 (14.3)0/20 (0.0)
  74/48 (8.3)1/28 (3.6)3/20 (15.0)
  88/48 (16.7)6/28 (21.4)2/20 (10.0)
  91/48 (2.1)0/28 (0.0)1/20 (5.0)
  101/48 (2.1)0/28 (0.0)1/20 (5.0)
  122/48 (4.2)2/28 (7.1)0/20 (0.0)
  141/48 (2.1)1/28 (3.6)0/20 (0.0)
  161/48 (2.1)0/28 (0.0)1/20 (5.0)
  171/48 (2.1)0/28 (0.0)1/20 (5.0)
  181/48 (2.1)0/28 (0.0)1/20 (5.0)
  241/48 (2.1)1/28 (3.6)0/20 (0.0)
  331/48 (2.1)0/28 (0.0)1/20 (5.0)
  481/48 (2.1)1/28 (3.6)0/20 (0.0)
  Unknown3/48 (6.2)3/28 (10.7)0/20 (0.0)

 

Table 2. Patient Outcomes
 
VariableNCohortP-valuea
Overall (N = 48)Greece (n = 28)Romania (n = 20)
aFisher’s exact test. bResponse data were unknown for 10 patients. AE: adverse event.
Best response, n/N (%)38b0.17
  Complete response21/38 (55.3)10/19 (52.6)11/19 (57.9)
  Partial response6/38 (15.8)3/19 (15.8)3/19 (15.8)
  No response or stable disease6/38 (15.8)4/19 (21.1)2/19 (10.5)
  Progressive disease5/38 (13.2)2/19 (10.5)3/19 (15.8)
Disease status at last known follow-up, n/N (%)480.031
  Disease progression19/48 (39.6)14/28 (50.0)5/20 (25.0)
  Progression free23/48 (47.9)9/28 (32.1)14/20 (70.0)
  Unknown6/48 (12.5)5/28 (17.9)1/20 (5.0)
Survival status at last known follow-up, n/N (%)480.003
  Alive28/48 (58.3)11/28 (39.3)17/20 (85.0)
  Dead19/48 (39.6)16/28 (57.1)3/20 (15.0)
  Unknown1/48 (2.1)1/28 (3.6)0/20 (0.0)
Primary cause of death, n/N (%)480.029
  Death from AE3/48 (6.2)3/28 (10.7)0/20 (0.0)
  Death from malignant disease under study6/48 (12.5)5/28 (17.9)1/20 (5.0)
  Death from other causes10/48 (20.8)8/28 (28.6)2/20 (10.0)
  Alive29/48 (60.4)12/28 (42.9)17/20 (85.0)

 

Table 3. Adverse Events in the Overall Study Population (N = 48)
 
Adverse eventn (%)
ALT: alanine aminotransferase; AST: aspartate aminotransferase.
Raised ALT, AST or bilirubin level5 (10.4)
Anxiety5 (10.4)
Allergic reactions3 (6.3)
Nausea/diarrhea3 (6.3)
Anemia2 (4.2)
Thrombocytopenia2 (4.2)
Hypertension2 (4.2)
Bleeding1 (2.1)
Atrial fibrillation1 (2.1)