Immune Thrombocytopenia Purpura
Transcript of Immune Thrombocytopenia Purpura
WHAT’S NEW IN ITP?
BUNDARIKA SUWANAWIBOON, MD.
DIVISION OF HEMATOLOGY
DEPARTMENT OF MEDICINE
FACULTY OF MEDICINE SIRIRAJ HOSPITAL
MAHIDOL UNIVERSITY
WHAT’S NEW IN ITP TREATMENT ?
Update on refractory ITP management
New Agent?No
New evidence?Yes
SECOND-LINE TREATMENT OF ADULT ITPTreatment Dose Time to initial
responseTime to peak
response• Rituximab 375 mg/m2/dose iv (4 weekly dose) 7-56 d 14-180 d
• Splenectomy 1-56 d 7-56 d
• Vincristine Up to 2 mg/dose iv (4-6 weekly doses) 7-14 d 7-42 d
• Vinblastine 0.1 mg/kg/dose iv (6 weekly doses) 7-14 d 7-42 d
• Danazol 400-800 mg po OD 14-90 d 28-180 d
• Azathioprine 2 mg/kg po OD 30-90 d 30-180 d
• Romiplostim 3-10 µg/kg weekly SC 5-14 d 14-60 d
• Eltrombopag 25-75 mg po OD 7-28 d 14-90 d
Rhodeghiero F et al. Blood.2009;113:2386-93, Provan D. Blood 2010;115:168-186
Thrombopoietin Receptor Agonists
Imbach P and Crowther M N Engl J Med. 2011;365:734-41
COMPARISON BETWEEN SPLENECTOMY, TPO-RA AND RITUXIMAB
Splenectomy Rituximab TPO-RAEfficacy High cure rate, Long-
term response 60%-70% at 5-10 y
Initial response 50%-60%, sustained response 20% at 3-5 y
Maintenance treatment response rate 60%-80%
Platelet count returns to baseline 2 wks after
d/c’d RxSafety Surgery related
morbidty, infectionInfusion-related side
effects, neutropenia, viral reactivation, serum
sickness
BM reticulin fibrosis, thrombosis, rebound
thrombocytopenia
Contraindication Unfit for surgery, Immunodeficiency,
secondary ITP
Active hepatitis B, allergy e.g. Serum sickness
Pregnancy, lactation
ASH 2011 recommendation
1B after failure of steroids
2C after failure of steroids 2C after failure of steroids
IS LONG-TERM ELTROMBOPAG USE SAFE AND EFFECTIVE?
Blood. 2013;121(3):537-545
Interim analysis of the ongoing open-label Eltrombopag eXTENded Dosing study Evaluate the safety and efficacy of eltrombopag in 299 pts treated up to 3 years Chronic ITP who completed a prior eltrombopag study (plt.< 30,000/µL and
insufficient response to ≥ 1 previous ITP treatment) Concomitant ITP treatment was allowed
EXTEND: STUDY DESIGN1. Eltrombopag initiated at 50 mg OD adjusted to keep plt. ≥ 50,000/µL
2. Reduce concomitant ITP medications, keep plt. ≥ 50,000/µL
3. Identify the minimal dose to maintain plt. ≥ 50,000/µL (25-75 mg OD or less frequently) ± minimal concomitant medication
4. Evaluate safety and efficacy of long-term dosing ± minimal concomitant medication
Blood. 2013;121(3):537-545
Study end points
■ Primary end points■ Safety and tolerability
parameters: AEs, lab test and ocular examination
■ Secondary end points■ Efficacy: proportion of pts
with plt ≥ 50,000/µL once, maximum duration of plt ≥ 50,000/µL, reduction in ITP medication, HRQoL, and WHO bleeding grades
Blood. 2013;121(3):537-545
Median platelets during EXTEND
Blood. 2013;121(3):537-545
Efficacy end points n = 299
Platelet count ≥ 50,000/µL at least once Splenectomized Nonsplenectomized Baseline plt. < 30,000/µL
85%80%88%80%
Median no. of cumulative wk with plt. ≥ 50,000/µL 44
Incidence (%) Remarks Thromboembolic
events5 VTE n = 12, ATE n = 9
Platelet prior to TEE 14,000-482,000/µL
Reoccurrence of thrombocytopenia
8
Bone marrow fibrosis
12 MF grade 0 n = 88, grade 1 n = 48, grade 2 n = 11
Hyperbilirubinemia
ALT increases
6
2
No pattern in the time to onset of HBLAsHBLA resolved despite continued Rx or after interruption of Rx
Cataracts 5 Headache 10 All grade 1 or 2
EXTEND: ADVERSE EVENTS
EXTEND STUDY: SUMMARY Long-term treatment with eltrombopag was generally safe.
No new or increased incidence of safety issues was identified
Treatment with eltrombopag for up to 3 years was effective in increasing and maintaining platelet counts
Blood. 2013;121(3):537-545
WHAT IS THE EFFICACY OF RITUXIMAB AS A SPLENECTOMY-SPARING OPTION IN PATIENTS PREVIOUSLY TREATED WITH STEROIDS ?
Multicenter, randomized, double-blinded, placebo-controlled trial Inclusion criteria: corticosteroid unresponsive primary ITP pts with
plt < 30,000/µL Primary outcome: rate of treatment failure within 78 weeks
Splenectomy or meeting criteria for splenectomy after week 12 Secondary outcome: response rate, relapse rate and duration of response
Lancet 2015;385:1653-1661
STUDY DESIGN1:1 randomization to receive rituximab or placebo in a double-blinded fashion
Treatment: 4 weekly infusion of rituximab 375 mg/m2 or placebo
Corticosteroid use with dose tapering to keep plt count >20,000/µL was allowed
Follow up visit q 6 wks during the study for 78 wks or for 12 wks after splenectomy
Lancet 2015;385:1653-1661
Rituximab (n=55)
Placebo (n=54)
Median age, yr 46 (27-61) 46 (28-60)
Female 40 (73%) 39 (72%)
Median plt, /x 109 cells/L 16 (6-27) 21 (9-29)
Median bleeding score 2 4
Treatment with corticosteroids 32 (58%) 24 (44%)
Median duration of ITP, weeks Newly diagnosed (0-3 mo) Persistent (3-12 mo) Chronic (>12 mo)
37 (8-288)18 (33%)13 (24%)24 (44%)
50 (14-211)12 (22%)16 (30%)26 (48%)
RESULTS (1)
Lancet 2015;385:1653-1661
Rituximab (n=55)
Placebo (n=54)
p value
Treatment failure Splenectomy
32 (58%)8 (15%)
37 (68%)14 (26%)
0.650.12
Overall response Loss of overall response Median duration of OR, wk
40 (73%)27 (68%)
36 (13-not reached)
36 (67%)28 (78%)7 (5-69)
0.150.010.01
Complete response Loss of complete response Median duration of CR,wk
28 (51%)14 (50%)
76 (32-not reached)
21 (39%)13 (62%)
49 (20-95)
0.120.190.19
Bleeding 21 (38%) 27 (50%) 0.08
Infection 22 (40%) 13 (24%) 0.09
RESULTS (2)
Lancet 2015;385:1653-1661
Time to treatment failure within 78 weeks
Lancet 2015;385:1653-1661
RITP STUDY: SUMMARY First double-blinded, placebo-controlled study to assess the long-term efficacy (78
weeks) of rituximab as second-line treatment in ITP
Rituximab does not significantly reduce the rate of long-term treatment failure compare with placebo
A small benefit of rituximab cannot be ruled out A longer duration of response and higher response rate was observed in the rituximab
group
TAKE HOME MESSAGE
Long-term data and results from large scale, randomized controlled studies of new agents/combination treatment is in needed in ITP
Balancing the risks and benefits of treatment on a case by case basis is necessary until more evidence is available
THANK YOU FOR YOUR ATTENTION
TITLE AND CONTENT LAYOUT WITH CHART
Category 1 Category 2 Category 3 Category 40
1
2
3
4
5
6
Series 1 Series 2 Series 3
TWO CONTENT LAYOUT WITH TABLE
First bullet point here Second bullet point here Third bullet point here
Group 1 Group 2
Class 1 82 95
Class 2 76 88
Class 3 84 90
TITLE AND CONTENT LAYOUT WITH SMARTART
Step 1 Title
Step 2 Title
Step 3 TitleStep 4 Title