[Abstract] Objective Liver function damage caused by Vanco has rarely been reported, but we found that liver function damage or even liver failure caused by Vanco is not rare and should be taken seriously. Methods Four cases of liver function damage caused by Vanco treatment for multiple myeloma were analyzed. All four patients had normal liver function before Vanco treatment, and all of them developed liver function damage during chemotherapy and were given liver protection. Conclusion: Vanco can cause liver function damage in the treatment of multiple myeloma.
[Keywords] Vanco, multiple myeloma, hepatic impairment
Vanco is a new targeted drug for multiple myeloma by inhibiting proteasome, and it has become the first-line treatment for multiple myeloma because of its good therapeutic effect. Its common side effects include thrombocytopenia, peripheral neuropathy, gastrointestinal reactions, and liver function damage is rarely mentioned, but we found that Vanco can cause liver function damage or even liver failure during treatment. The clinical data of four patients are reported as follows.
1 Data and methods
1.1 Case data
Four patients with relapsed refractory multiple myeloma were treated with Vanco in our department from August 2008 to May 2009, 3 males and 1 female, aged 46 to 60 years, κ light chain type 2 cases, non-secretory type 1 case, lgGλλ biclonal type 1 case, stage IIIb 3 cases, stage IIIA 1 case. The previous chemotherapy regimens used were: VAD, MP, M2, DECP ,CTD, etc.
1.2 Treatment method
Patient 1: Vanco 1.75mg/d d1, 4, 8, 11 Methylprednisolone 80mg/d d1, 4, 8, 11 Reactive arrest 100mg/d d1-21.
Patient 2: Vanco 1.75mg/d d1,4,8,11 Methylprednisolone 40-80mg/d d1,4,8,11 .
Patient 3: Vanco 2.3mg/d d1,4,8,11 Methylprednisolone 120mg/d d1,4,8,11 and Relidomide 10mg d1-14.
Patient 4: Vanco 1.75mg/d d1,4,8,11 methylprednisolone 80-120mg/d d1,4,8,11.
2. Results:
2.1 Changes in liver function indexes
ALT
(U/L)
AST
(U/L)
r-GT
(U/L)
TBIL
(umol/l)
DBIL
(umol/l)
IBIL (umol/l)
ALP
(U/l)
Pre-treatment Post-treatment
Pre-treatment Post-treatment
Pre-treatment Post-treatment
Pre-treatment Post-treatment
Pre-treatment Post-treatment
Before Treatment After Treatment
Before treatment After treatment
Patient 1
6.2 511.6
22 1434.6
15.8 233.1
7.7 42.6
0.8 30.2
6.9 6.9
48.8 177.9
Patients2
24.2 371.6
17.7 171.4
123.8 96.4
12 28.9
0.2 6.5
11.8 22.4
81.7 139.9
Patients3
42.1 93.4
25 36.8
60.8 57.2
25.4 16.5
5 2.3
20.4 14.2
85 64.5
Patients4
31.6 294.5
36.3 69.4
21.4 60.5
14 9.5
3.3 1.8
10.7 7.7
70.5 52.5
The patients all had normal liver function before chemotherapy and no previous history of liver disease such as viral hepatitis. The patients all had liver function damage during chemotherapy, mostly peaking after the third injection. One patient had a 70-fold increase in transaminases, had coagulation abnormalities and developed liver failure. The liver function index gradually returned to normal after discontinuation of Vanco in severe cases. The liver ultrasound did not show any significant abnormality.
2.2 Therapeutic effect
VGPR (very good partial remission) in 1 case, PR (partial remission) in 1 case, SD (stable disease) in 1 case, PD (disease progression) in 1 case
3. Discussion
Multiple myeloma is still incurable even when intensive treatment is given. Therefore, new drugs are needed to improve the prognosis. Vanco (bortezomib) is the first proteasome inhibitor that showed significant anti-myeloma activity. Overall survival at 1 year was divided into 80% versus 66% for single-agent versus dexamethasone, and the median progression-free time was prolonged in 78% of patients [1]. Further studies confirmed the synergistic effect of Vanco with conventional chemotherapy combination, further increasing the efficacy. In addition Vanco is well tolerated and most side effects are mild to moderate and manageable, the most common side effects being peripheral neuropathy, thrombocytopenia, and gastrointestinal reactions. To date there is limited information on hepatic impairment caused by Vanco, Rosiñol L [3] et al. reported a case of severe hepatitis in a patient with recurrent myeloma treated with Vanco, recognizing this rare potential side effect with the aim that interruption of Vanco treatment should be considered for suspected serious hepatic side effects. Three of the four patients we reported were relapsed refractory patients after multiple chemotherapy treatments. Three of them had received previous chemotherapy with Vancor without liver impairment, and one had liver impairment on the first dose of Vancor, suggesting that liver impairment was not directly related to the duration of Vancor use. There does not appear to be a direct relationship with cumulative dose either, as the most severe case of liver failure was the first use. The side effects of hepatic impairment were not more pronounced in patients with better (or worse) outcomes. In conclusion, hepatic impairment caused by Vanco may be related to increased metabolism of the drug from the liver to the liver, individual differences in sensitivity, and the reserve function of the liver.
The SUMMIT trial included patients with significantly elevated bilirubin or transaminases and found no significant effect of 8 cycles of Vanco on bilirubin, transaminases, and alkaline phosphatase. However, hepatic impairment due to Vanco has now been reported [2]. The evaluation of Vanco on liver function damage is ongoing. Because Vanco is mainly metabolized by cytochrome enzymes, significant hepatic impairment may affect the metabolism of Vanco. Recent data suggest that patients with mild hepatic impairment should be closely monitored while receiving Vanco and that patients with significant hepatic impairment, i.e., more than 2.5-3 times the upper limit of normal liver enzyme values, should not receive Vanco. Patients with mild to moderate liver function abnormalities (i.e., transaminases or bilirubin 2-3 times normal) can be safely treated with close monitoring and timely dose adjustments.