IDELALISIB PLUS AN ANTI-CD20 ANTIBODY IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) WHO ARE HBV CORE ANTIBODY POSITIVE: SIMILAR PATTERNS OF LIVER TEST ABNORMALITIES
(Abstract release date: 05/19/16)
EHA Library. Robak T. 06/09/16; 132612; E1063
Prof. Tadeusz Robak
Contributions
Contributions
Abstract
Abstract: E1063
Type: Eposter Presentation
Background
Increased hepatitis B virus (HBV) reactivation risk has been reported in patients (pts) undergoing treatment with anti-CD20 therapies, including rituximab (R) and ofatumumab (O).1 Reactivation can also occur after HBV surface antigen (HBsAg) loss, especially in immuno-compromised pts.2,3 A high rate of reactivation has been reported in such pts receiving an anti-CD20 antibody + chemotherapy.4 The incidence of transaminase elevation in CLL pts who are core antibody positive (anti-HBc+)/ HBsAg-/HBV PCR- and receiving anti-CD20 + kinase inhibitors including idelalisib (IDELA) has not been reported.
Aims
The objective of this analysis was to characterize the patterns of changes in liver tests in pts with CLL and anti-HBc+/ HBsAg-/HBV PCR- and receiving IDELA + anti-CD20.
Methods
The patterns of changes in liver tests were analyzed among 477 pts with relapsed/refractory (R/R) CLL treated with IDELA + R vs placebo + R (NCT01539512) or IDELA + O vs O (NCT01659021). Pts with anti-HBc+/HBsAg- were enrolled only if they were HBV PCR- by quantitative PCR (qPCR). Pts who were anti-HBc+/HBsAg- at screening were monitored for potential HBV reactivation (manifested as detectable HBV DNA by qPCR).
Results
During the study period beginning May 2012, 283 pts received IDELA + anti-CD20 therapy (110 IDELA + R; 173 IDELA + O) and 194 pts received anti-CD20 monotherapy (108 R; 86 O). Of 477 pts analyzed, 390 pts were anti-HBc-/HBsAg- (86 IDELA + R; 152 IDELA + O; 79 R; 73 O); 85 pts were anti-HBc+/HBsAg-/HBV PCR- (24 IDELA + R; 21 IDELA + O; 28 R; 12 O); 2 pts had missing data (1 R; 1 O). Of the 85 pts who were anti-HBc+, 3 had a prior history of HBV infection and 41 (22/45 on IDELA+anti-CD20 and 19/40 on anti-CD20) had received IV immunoglobulin (IVIG) before screening for treatment of hypogammaglobulinemia; 5 pts on IDELA+anti-CD20 and 3 on anti-CD20 received anti-HBV prophylaxis on-study. In the subgroup analysis, no significant difference in liver test abnormalities was detected between anti-HBc+/HBsAg- and anti-HBc-/HBsAg- subgroups in pts receiving IDELA + anti-CD20 or anti-CD20 monotherapy (table).
Conclusion
Prior exposure to Hep B does not appear to be a risk factor associated with liver test abnormalities in pts treated with IDELA+anti-CD20. References1. Mitka M. JAMA. 2013;310(16):16642. Hoofnagle JH. Hepatology. 2009;49(5 Suppl):S156-653. Mikulska M, et al. Clin Microbiol Infect. 2014;20:O694-7014. Seto WK, et al. J Clin Oncol. 2014;32(33):3736-43
Session topic: E-poster
Keyword(s): CD20, Chronic lymphocytic leukemia, Clinical trial
Type: Eposter Presentation
Background
Increased hepatitis B virus (HBV) reactivation risk has been reported in patients (pts) undergoing treatment with anti-CD20 therapies, including rituximab (R) and ofatumumab (O).1 Reactivation can also occur after HBV surface antigen (HBsAg) loss, especially in immuno-compromised pts.2,3 A high rate of reactivation has been reported in such pts receiving an anti-CD20 antibody + chemotherapy.4 The incidence of transaminase elevation in CLL pts who are core antibody positive (anti-HBc+)/ HBsAg-/HBV PCR- and receiving anti-CD20 + kinase inhibitors including idelalisib (IDELA) has not been reported.
Aims
The objective of this analysis was to characterize the patterns of changes in liver tests in pts with CLL and anti-HBc+/ HBsAg-/HBV PCR- and receiving IDELA + anti-CD20.
Methods
The patterns of changes in liver tests were analyzed among 477 pts with relapsed/refractory (R/R) CLL treated with IDELA + R vs placebo + R (NCT01539512) or IDELA + O vs O (NCT01659021). Pts with anti-HBc+/HBsAg- were enrolled only if they were HBV PCR- by quantitative PCR (qPCR). Pts who were anti-HBc+/HBsAg- at screening were monitored for potential HBV reactivation (manifested as detectable HBV DNA by qPCR).
Results
During the study period beginning May 2012, 283 pts received IDELA + anti-CD20 therapy (110 IDELA + R; 173 IDELA + O) and 194 pts received anti-CD20 monotherapy (108 R; 86 O). Of 477 pts analyzed, 390 pts were anti-HBc-/HBsAg- (86 IDELA + R; 152 IDELA + O; 79 R; 73 O); 85 pts were anti-HBc+/HBsAg-/HBV PCR- (24 IDELA + R; 21 IDELA + O; 28 R; 12 O); 2 pts had missing data (1 R; 1 O). Of the 85 pts who were anti-HBc+, 3 had a prior history of HBV infection and 41 (22/45 on IDELA+anti-CD20 and 19/40 on anti-CD20) had received IV immunoglobulin (IVIG) before screening for treatment of hypogammaglobulinemia; 5 pts on IDELA+anti-CD20 and 3 on anti-CD20 received anti-HBV prophylaxis on-study. In the subgroup analysis, no significant difference in liver test abnormalities was detected between anti-HBc+/HBsAg- and anti-HBc-/HBsAg- subgroups in pts receiving IDELA + anti-CD20 or anti-CD20 monotherapy (table).
| IDELA+anti-CD20 | anti-CD20 | |||
| anti-HBc+ (n=45) | anti-HBc- (n=238) | anti-HBc+ (n=40) | anti-HBc- (n=152) | |
| Grade ≥3 ALT/AST↑, n (%) | 7 (15.6) | 25 (10.5) | 1 (2.5) | 1 (0.7) |
| P value | 0.449 | 0.379 | ||
| Med Time to Onset, wks | 6.9 | 8.1 | - | - |
| Grade ≥3 total bilirubin↑, n (%) | 1 (2.2) | 3 (1.3) | 0 (0) | 1 (0.7) |
| Grade ≥3 GGT↑, n (%) | 1 (2.2) | 13 (5.5) | 3 (7.5) | 1 (0.7) |
| Drug discontinuation due to hepatic-related TEAE, n (%) | 0 (0) | 8 (3.4) | 0 (0) | 0 (0) |
Conclusion
Prior exposure to Hep B does not appear to be a risk factor associated with liver test abnormalities in pts treated with IDELA+anti-CD20. References1. Mitka M. JAMA. 2013;310(16):16642. Hoofnagle JH. Hepatology. 2009;49(5 Suppl):S156-653. Mikulska M, et al. Clin Microbiol Infect. 2014;20:O694-7014. Seto WK, et al. J Clin Oncol. 2014;32(33):3736-43
Session topic: E-poster
Keyword(s): CD20, Chronic lymphocytic leukemia, Clinical trial
Abstract: E1063
Type: Eposter Presentation
Background
Increased hepatitis B virus (HBV) reactivation risk has been reported in patients (pts) undergoing treatment with anti-CD20 therapies, including rituximab (R) and ofatumumab (O).1 Reactivation can also occur after HBV surface antigen (HBsAg) loss, especially in immuno-compromised pts.2,3 A high rate of reactivation has been reported in such pts receiving an anti-CD20 antibody + chemotherapy.4 The incidence of transaminase elevation in CLL pts who are core antibody positive (anti-HBc+)/ HBsAg-/HBV PCR- and receiving anti-CD20 + kinase inhibitors including idelalisib (IDELA) has not been reported.
Aims
The objective of this analysis was to characterize the patterns of changes in liver tests in pts with CLL and anti-HBc+/ HBsAg-/HBV PCR- and receiving IDELA + anti-CD20.
Methods
The patterns of changes in liver tests were analyzed among 477 pts with relapsed/refractory (R/R) CLL treated with IDELA + R vs placebo + R (NCT01539512) or IDELA + O vs O (NCT01659021). Pts with anti-HBc+/HBsAg- were enrolled only if they were HBV PCR- by quantitative PCR (qPCR). Pts who were anti-HBc+/HBsAg- at screening were monitored for potential HBV reactivation (manifested as detectable HBV DNA by qPCR).
Results
During the study period beginning May 2012, 283 pts received IDELA + anti-CD20 therapy (110 IDELA + R; 173 IDELA + O) and 194 pts received anti-CD20 monotherapy (108 R; 86 O). Of 477 pts analyzed, 390 pts were anti-HBc-/HBsAg- (86 IDELA + R; 152 IDELA + O; 79 R; 73 O); 85 pts were anti-HBc+/HBsAg-/HBV PCR- (24 IDELA + R; 21 IDELA + O; 28 R; 12 O); 2 pts had missing data (1 R; 1 O). Of the 85 pts who were anti-HBc+, 3 had a prior history of HBV infection and 41 (22/45 on IDELA+anti-CD20 and 19/40 on anti-CD20) had received IV immunoglobulin (IVIG) before screening for treatment of hypogammaglobulinemia; 5 pts on IDELA+anti-CD20 and 3 on anti-CD20 received anti-HBV prophylaxis on-study. In the subgroup analysis, no significant difference in liver test abnormalities was detected between anti-HBc+/HBsAg- and anti-HBc-/HBsAg- subgroups in pts receiving IDELA + anti-CD20 or anti-CD20 monotherapy (table).
Conclusion
Prior exposure to Hep B does not appear to be a risk factor associated with liver test abnormalities in pts treated with IDELA+anti-CD20. References1. Mitka M. JAMA. 2013;310(16):16642. Hoofnagle JH. Hepatology. 2009;49(5 Suppl):S156-653. Mikulska M, et al. Clin Microbiol Infect. 2014;20:O694-7014. Seto WK, et al. J Clin Oncol. 2014;32(33):3736-43
Session topic: E-poster
Keyword(s): CD20, Chronic lymphocytic leukemia, Clinical trial
Type: Eposter Presentation
Background
Increased hepatitis B virus (HBV) reactivation risk has been reported in patients (pts) undergoing treatment with anti-CD20 therapies, including rituximab (R) and ofatumumab (O).1 Reactivation can also occur after HBV surface antigen (HBsAg) loss, especially in immuno-compromised pts.2,3 A high rate of reactivation has been reported in such pts receiving an anti-CD20 antibody + chemotherapy.4 The incidence of transaminase elevation in CLL pts who are core antibody positive (anti-HBc+)/ HBsAg-/HBV PCR- and receiving anti-CD20 + kinase inhibitors including idelalisib (IDELA) has not been reported.
Aims
The objective of this analysis was to characterize the patterns of changes in liver tests in pts with CLL and anti-HBc+/ HBsAg-/HBV PCR- and receiving IDELA + anti-CD20.
Methods
The patterns of changes in liver tests were analyzed among 477 pts with relapsed/refractory (R/R) CLL treated with IDELA + R vs placebo + R (NCT01539512) or IDELA + O vs O (NCT01659021). Pts with anti-HBc+/HBsAg- were enrolled only if they were HBV PCR- by quantitative PCR (qPCR). Pts who were anti-HBc+/HBsAg- at screening were monitored for potential HBV reactivation (manifested as detectable HBV DNA by qPCR).
Results
During the study period beginning May 2012, 283 pts received IDELA + anti-CD20 therapy (110 IDELA + R; 173 IDELA + O) and 194 pts received anti-CD20 monotherapy (108 R; 86 O). Of 477 pts analyzed, 390 pts were anti-HBc-/HBsAg- (86 IDELA + R; 152 IDELA + O; 79 R; 73 O); 85 pts were anti-HBc+/HBsAg-/HBV PCR- (24 IDELA + R; 21 IDELA + O; 28 R; 12 O); 2 pts had missing data (1 R; 1 O). Of the 85 pts who were anti-HBc+, 3 had a prior history of HBV infection and 41 (22/45 on IDELA+anti-CD20 and 19/40 on anti-CD20) had received IV immunoglobulin (IVIG) before screening for treatment of hypogammaglobulinemia; 5 pts on IDELA+anti-CD20 and 3 on anti-CD20 received anti-HBV prophylaxis on-study. In the subgroup analysis, no significant difference in liver test abnormalities was detected between anti-HBc+/HBsAg- and anti-HBc-/HBsAg- subgroups in pts receiving IDELA + anti-CD20 or anti-CD20 monotherapy (table).
| IDELA+anti-CD20 | anti-CD20 | |||
| anti-HBc+ (n=45) | anti-HBc- (n=238) | anti-HBc+ (n=40) | anti-HBc- (n=152) | |
| Grade ≥3 ALT/AST↑, n (%) | 7 (15.6) | 25 (10.5) | 1 (2.5) | 1 (0.7) |
| P value | 0.449 | 0.379 | ||
| Med Time to Onset, wks | 6.9 | 8.1 | - | - |
| Grade ≥3 total bilirubin↑, n (%) | 1 (2.2) | 3 (1.3) | 0 (0) | 1 (0.7) |
| Grade ≥3 GGT↑, n (%) | 1 (2.2) | 13 (5.5) | 3 (7.5) | 1 (0.7) |
| Drug discontinuation due to hepatic-related TEAE, n (%) | 0 (0) | 8 (3.4) | 0 (0) | 0 (0) |
Conclusion
Prior exposure to Hep B does not appear to be a risk factor associated with liver test abnormalities in pts treated with IDELA+anti-CD20. References1. Mitka M. JAMA. 2013;310(16):16642. Hoofnagle JH. Hepatology. 2009;49(5 Suppl):S156-653. Mikulska M, et al. Clin Microbiol Infect. 2014;20:O694-7014. Seto WK, et al. J Clin Oncol. 2014;32(33):3736-43
Session topic: E-poster
Keyword(s): CD20, Chronic lymphocytic leukemia, Clinical trial
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