Table 3. Study characteristics and clinical outcome of rituximab-treated patients with mixed cryoglobulinemia (MC) reported in the literature.
| MC classification | Rituximab | Outcome CR/PR/NR(%) |
Renal Involvement (N.) |
Biopsy Proven (Y/N) |
Renal Outcome* CR/PR/NR (%) | Flare-related re-treament | Adverse Effects | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Author (Year) | Pts N. | Study | Follow-up (months) | Essential | HCV+ | Protocol | Main indication | ||||||
| Sansonno (2003) |
20 | PCS | 12 | - | 20 | 375mg/m2 x 4 weekly | MC-Overall Skin Vasculitis 16 Skin Ulcers 7 Neuropathy 12 |
80/0/20 75/12/12 42/29/29 50/40/10 |
1 | N | 0/0/100 | NR | 3 Mild |
| Zaja (2003) |
15 | PCS | 9-31 | 3 | 12 | 375mg/m2 x 4 weekly | Skin Vasculitis 12 Neuropathy 7 B-NHL 3 Skin Ulcers 5 |
75//8/17 86/14/0 33/64/0 100/0/0 |
2 | Y | 50/0/50 | NR | 1 retinal artery thrombosis and 2 panniculitis |
| De Vita (2007) |
28 | PCS | 3 to 60 | NA | NA | 375 mg/m 2 weekly for 4 weeks (21/28) or 1 g x 2 (7/28) administered on days 1 and 15. |
Skin Vasculitis19 skin ulcers8 neuropathy 15 |
68/NR/NR 63/NR/NR 86/NR/NR |
8 | Y | 37/NR/NR at month +6 | 9 | 3 first infusion reactions, 1 retinal artery thrombosis, 1panniculitis, 1severe infection, 1severe transient neutropenia, 1haemorrhagic alveolitis, 2transaminase elevations |
| Saadoun (2008) |
16 | PCS | mean 19.4 (SD 3.6) |
- | 16 | 375mg/m2 x 4 weekly+peg-IFN-α and RBV | MC-Overall Neuropathy 13 B-NHL 3 Skin Ulcers 2 |
32/31/6 77/15/8 67/33/0 100/0/0 |
7 | N | 57/0/43 | NR | 12 mild |
| Roccatello (2008) |
12 | PCS | 24 | 1 | 11 | 375mg/m2 x 4 weekly+2 monthly infusions | Skin Ulcer 3 bone marrow clonal restriction 3 |
100/0/0 100/0/0 |
7 | Y | 80/20/0 | NR | None |
| Sène (2009) |
22 | CS | - | - | 22 | 375mg/m2 x 4 weekly (18 patients) 1 g x 2 administered on days 1 and 15 (4 patients) |
Purpura 17 polyneuropathy 19 | NR | 10 | Y | NR | NR | 27.3% infusion relatedadversereactions. 4 severe flare of MC vasculitis 2 serum sickness syndrome |
| Cavallo (2009) |
13 | PCS | 12 | 1 | 12 | 375mg/m2 x 4 weekly+2 monthly infusions | Neuropathy | Asthenia 83/17/0 Pareshesia50/25/25 Burning feet 67/33/0 |
None | N/A | NR | NR | NR |
| Terrier (2009) |
32 | PCS | 24 | - | 32 | 375mg/m2 x 4 weekly+peg-IFN-α and RBV (20 patients) and 375mg/m2 x 4 weekly alone (12) |
Overall Overall |
80/15/5 58/9/33 |
NR | N | NR | 15% 33% |
serum sickness (n = 6), neutropenia (n = 2), varicella zoster virus infection (n = 1), and subcutaneous extravasation of rituximab (n = 1). |
| Saadoun (2010) |
39 | PCS | 6.8 (SD 4.7) | - | 39 | 375mg/m2 x 4 weekly+peg-IFN-α and RBV | Overall Purpura 29 polyneuropathy 28 arthralgia 15 |
73/23/4 83/0/17 50/0/50 |
21 | N | 80/NR/NR | RTX in 2 and peg-IFN-α and RBV in 1 | included serum sickness in 4, neutropenia and 2 Streptococcus pneumoniaepneumopathy, varicella-zoster virus infection, anderysipela (n =1) |
| Terrier (2010) |
23 | PCS | 22.2 (SD16.7) | 8 | 0 | 375mg/m2 x 4 weekly (18 patients) 1 g x 2 administered on days 1 and 15 (3 patients) R-CHOP (1) Fludarabin+Cylophosphamide (1) |
Skin Vasculits 19 Neuropathy 12 |
74//16/0 84/16/0 |
7 | N | 57/13/30 | 9 | Severe infections 6 (3 death), mild adverse events: 2, serum sickness-like syndrome 1 |
| Dammacco (2010) |
37 | RCT | 36 | - | 37 | 375mg/m2 x 4 weeklyfollowed by two 5-monthly infusions associated to peg-IFN-α and RBV |
HCV-related MC cryoglobulinemia with biopsy proven chronic hepatitis | 55/ 23/23 | 5 | N | 80/0/20 | NR | 3 mild infusions-related fever episode |
| Petrarca (2010) |
19 | PCS | 6 | - | 19 | 375mg/m2 x 4 weekly | Skin Vasculitis 17 Skin Ulcers 3 |
82/18/0 100/0/0 |
5 | Y | 67/33/0 | NR | None |
| Ferri (2011) |
87 | RCS | 6 | 5 | 80 | 375mg/m2 x 4 weekly (59 patients) 1 g x 2 administered on days 1 and 15 (18 patients) 375mg/m2 x 4 weekly+2 monthly infusions (10 patients) |
Skin Vasculits 24 Neuropathy 30 Nephropathy 38 B-NHL 6 Abdominal vasculits 1 |
62/8/29 50/30/20 50/30/20 50/45/5 100/0/0 |
29 | Not detailed | 62/31/7 | NR | Infusion-related reactions 4 Infections 4 Mild adverse events 8 |
| Gragnani (2011) |
21 | RCS | 6 | - | 21 | 375mg/m2 x 4 weekly | Purpura 19 Neuropathy 19 Skin Ulcers 3 |
68/0/32 58/0/42 67/0/33 |
5 | N | 60/0/40 | NR | NR |
| Sneller (2012) |
12 | RCT | 12 | - | 12 | 375mg/m2 x 4 weekly | MC-Overall Purpura 12 Neuropathy 9 Skin Ulcers 4 |
50/0/50 | 4 | N | NR | 3 | 1 sever Fever 7 mild adverse effects |
| Visentini (2011) |
27 | PCS | 12 | - | 27 | 250 mg/m2 x2 weekly | Overall at 3 months Purpura 24 Neuropathy 23 Skin Ulcers 9 |
11/59/30 65/30/5 40/45/15 67/23/10 |
13 | N | 40/30/30 | 8 | 1 serum sickness syndrome, 1 pneumonia, 1 anaphylaxis |
| De Vita (2012) |
28 | RCT | 24 | 3 | 25 | 1 g x 2 administered on days 1 and 15 (18 patients) | Neuropathy 16 Skin Ulcers 5 |
12/82/6 80/0/20 |
7 | Y | 29/29/42 | NR | 2 serious infections, 1arterial hypotension followed by angina pectoris |
| Stasi (2014) |
14 | PCS | 6 | - | 12 | 1 g x 2 administered on days 1 and 15 (18 patients) | Purpura 11 Neuropathy 7 Skin Ulcers 1 |
90/0/10 at 3 months 42/0/68 at 3 months 100/0/0 at 3 months |
2 | N | 50/0/50 at 3 months | NR | NR |
| Visentini (2015) |
52 (evaluable 48) |
PCS | 12 | - | 52 | 250 mg/m2, given twice at one-week interval |
Overall Skin ulcers 14 Neuropathy 47 Nephropathy 22 |
50/31/19 | 22** | N | NR | NR | 6 adverse (1 anaphylaxis) |
| Roccatello (2016) |
31 | PCS | 72.47 (30-148) |
4 | 26 | 375mg/m2 × 4 weekly +2 monthly infusions | Overall Skin ulcers 7 Nephropathy 16 Neuropathy 26 Paresthesia Burning feet Weakness |
65/32/3 100/0/0 85/5/10 74/16/10 89/5/6 |
16 | Y | 75/19/6 | 9 | Drug-related bradycardia N=2 Arterial pressure lowering until 100/60mmHg N=2 UTI N=2 |
*
calculated on those with renal involvement; PCS, prospective cohort study, RCT, randomized controlled trial; CS, cross-sectional, SD, standard deviation; Peg-IFN-α, pegylated interferon- α; RBV, ribavirin; MPGN, membranoproliferative glomerulonephritis; UTI, urinary tract infections; CR, complete response, PR, partial response, NR, no response; N/A, not applicable. **the rate of renal involvement is not detailed in the 48 evaluable patients.