Development of New Drugs for Autoimmune Hemolytic Anemia
Abstract
1. Introduction
2. Classification
3. Treatment of Warm Autoimmune Hemolytic Anemia
3.1. Corticosteroids
3.2. Rituximab
3.3. Subsequent Therapies
4. Treatment of Cold Agglutinin Disease
5. Novel Agents
5.1. B-Cell-Directed Therapies
5.1.1. PI3K Inhibition
Medication | Type of AIHA | Type of Study | Concurrent Disease | Regimen | Efficacy/Response Rate | Reference |
---|---|---|---|---|---|---|
Idelalisib | Mixed | Case report | CLL | 175 mg bid, rituximab, steroids | Hemoglobin increment 3.6 g/dL | [68] |
Warm | Retrospective, N = 19 | CLL | 150 mg bid ± rituximab | ORR 95%, 71% discontinued steroids | [69] | |
Parsaclisib | Warm/cold/mixed | Open-label, phase 2 | N/A | 1 mg daily, 2.5 mg daily | CR 33%, PR 66.7% | [73] |
Ibrutinib | N/A | Retrospective, N = 21 | CLL | 420 mg daily | Hemoglobin increment 2 g/dL | [75] |
Warm | Case report | MCL | 560 mg daily | Hemoglobin increment 4.1 g/dL | [76] | |
Mixed | Pilot study, N = 2 | N/A | 280 mg daily and 420 mg daily | CR 100% | [77] | |
Cold | Retrospective, N = 10 | CLL/SLL, WM | N/A | CR 90%, PR 10% | [78] | |
Sirolimus | Mixed | Case report | Post allo-SCT | 3 mg/m2 on day 1 followed by 1 mg/m2 daily | CR | [79] |
Mixed and warm | Case series, N = 4 | Solid organ transplant | N/A | Response rate 100% | [80] | |
N/A | Retrospective, N = 14 | N/A | 1–3 mg daily | ORR 85.7%, CR 57.1% | [81] | |
N/A | Prospective, N = 2 | N/A | 2–2.5 mg/m2 daily | CR 50%, PR 50% | [82] |
5.1.2. BTK Inhibition
5.1.3. mTOR Inhibition
5.2. Phagocytosis Inhibition
5.2.1. Syk Inhibition
5.2.2. FcRn Inhibition
5.3. Plasma Cell-Directed Therapy
5.3.1. Proteasome Inhibition
5.3.2. CD38 Monoclonal Antibody
Medication | Type of AIHA | Type of Study | Concurrent Disease | Regimen | Efficacy/Response Rate | Reference |
---|---|---|---|---|---|---|
Bortezomib | Mixed | Case report | Post allo-SCT | 1.3 mg/m2 day 1, 4, 8, 11 | Transfusion independent | [162] |
N/A | Case report | Post solid organ transplant | 1.3 mg/m2 day 1 | Transfusion independent | [163] | |
N/A | Case report | Post allo-SCT | 1.3 mg/m2 day 1, 8, 15, 22 | Transfusion independent | [164] | |
N/A | Case report | Post allo-SCT | 1.3 mg/m2 day 1, 4, 8, 11 for 2 cycles | Transfusion independent | [165] | |
Warm | Case report | Post solid organ transplant | 1.3 mg/m2 day 1, 4, 8, 11 monthly | Transfusion independent | [166] | |
Mixed | Case report | Post solid organ transplant | 1.3 mg/m2 D 1, 4, 8, 11 | CR | [167] | |
N/A | Case report | SLE | 1.3 mg/m2 D 1, 4, 8, cyclophosphamide, steroids | CR | [172] | |
Warm | Retrospective, N = 7 | N/A | 1.3 mg/m2 D 1, 8, 15, 22, rituximab, steroids | ORR 85.71% | [171] | |
Warm | Retrospective, N = 7 | N/A | 1.3 mg/m2 D 1, 4, 8, 11, rituximab | CR 71.4% | [173] | |
Warm | Retrospective, N = 8 | N/A | 1.3 mg/m2 D 1, 4, 8, 11, steroids | ORR 75% | [168] | |
Warm | Case report | N/A | 1.3 mg/m2 D 1, rituximab | PR | [174] | |
Warm | Case series, N = 2 | N/A | 1.3 mg/m2 D 1, 4, 8, 11, dexamethasone | PR 2/2 | [169] | |
Warm | Case series, N = 4 | N/A | 1.3 mg/m2 D 1, 4, 8, 11, dexamethasone | CR 1/4, PR 2/4 | [169] | |
Cold | Open-label, phase 2 | 42.9% B-LPD | 1.3 mg/m2 D 1, 4, 8, 11 | ORR 31.6% | [54] | |
Daratumumab | N/A | Case report | Post allo-SCT | 16 mg/kg weekly in 4 doses | CR | [182] |
N/A | Retrospective, N = 3 | Post allo-SCT | N/A | CR 67% | [183] | |
N/A | Retrospective, N = 3 | Post allo-SCT | N/A | CR 67% PR 33% | [184] | |
N/A | Case report | Post allo-SCT | 16 mg/kg weekly in 6 doses | CR | [185] | |
Warm | Case report | N/A | 16 mg/kg weekly | CR | [186] | |
Warm | Retrospective, N = 4 | 50% post allo-SCT | 16 mg/kg weekly | ORR 100%, CR 50% | [188] | |
Cold | Case report | N/A | 16 mg/kg weekly | Response | [187] |
5.4. Complement Inhibition
6. Conclusions
Author Contributions
Funding
Informed Consent Statement
Conflicts of Interest
References
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Xiao, Z.; Murakhovskaya, I. Development of New Drugs for Autoimmune Hemolytic Anemia. Pharmaceutics 2022, 14, 1035. https://doi.org/10.3390/pharmaceutics14051035
Xiao Z, Murakhovskaya I. Development of New Drugs for Autoimmune Hemolytic Anemia. Pharmaceutics. 2022; 14(5):1035. https://doi.org/10.3390/pharmaceutics14051035
Chicago/Turabian StyleXiao, Zhengrui, and Irina Murakhovskaya. 2022. "Development of New Drugs for Autoimmune Hemolytic Anemia" Pharmaceutics 14, no. 5: 1035. https://doi.org/10.3390/pharmaceutics14051035
APA StyleXiao, Z., & Murakhovskaya, I. (2022). Development of New Drugs for Autoimmune Hemolytic Anemia. Pharmaceutics, 14(5), 1035. https://doi.org/10.3390/pharmaceutics14051035