Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia
Abstract
:1. Introduction
2. Cytotoxic Chemotherapy
Regimen | Agents | CR | TRM or 30 Day Mortality | Reference |
---|---|---|---|---|
HIDAC | Cytarabine 3 g/m2 every 12 h days 1–6 | 32%–47% | 12%–15% | [12,13] |
FLAG FLAG-IDA | Fludarabine 30 mg/m2 days 1–5 | 48%–55% | 10%–11% | [14,15] |
Cytarabine 2 g/m2 days 1–5 | ||||
G-CSF 5 mcg/kg day 0 until ANC recovery | ||||
Fludarabine 30 mg/m2 days 1–5 | 63% | 17% | [16] | |
Cytarabine 2 g/m2 days 1–5 | ||||
G-CSF 300 mcg day 0 until ANC recovery | ||||
Idarubicin 8 mg/m2 days 1–3 | ||||
FLA | Fludarabine 30 mg/m2 days 1–5 | 61% | 7% | [17] |
Cytarabine 2 g/m2 days 1–5 | ||||
CLAG CLAG-M | Cladribine 5 mg/m2 days 2–6 | 38%–50% | 0%–17% | [18,19,20] |
Cytarabine 2 g/m2 days 2–6 | ||||
G-CSF 300 mcg days 1–6 | ||||
Cladribine 5 mg/m2 days 1–5 | 50%–58% (53% after first course) | 0%–7% | [18,21] | |
Cytarabine 2 g/m2 days 1–5 | ||||
G-CSF 300 mcg days 0–5 | ||||
Mitoxantrone 10 mg/m2 days 1–3 | ||||
MEC | Mitoxantrone 6 mg/m2 days 1–6 | 59%–66% | 3%–6% | [22,23] |
Etoposide 80 mg/m2 days 1–6 | ||||
Cytarabine 1 g/m2 days 1–6 | ||||
Mitoxantrone 8 mg/m2 days 1–5 | 18%–24% | 7%–11% | [20,24,25] | |
Etoposide 100 mg/m2 days 1–5 | ||||
Cytarabine 1 mg/m2 days 1–5 | ||||
MEC/Decitabine | Decitabine 20 mg/m2 days 1–10 | 30% (CR + CRp + CRi = 50%) | 20% | [26] |
Mitoxantrone 8 mg/m2 days 16–20 | ||||
Etoposide 100 mg/m2 days 16–20 | ||||
Cytarabine 1 mg/m2 days 16–20 | ||||
EMA-86 | Mitoxantrone 12 mg/m2 days 1–3 | 60% | 11% | [27] |
Cytarabine 500 mg/m2 CI days 1–3 & 8–10 | ||||
Etoposide 200 mg/m2 CI days 8–10 | ||||
MAV | Mitoxantrone 10 mg/m2 days 4–8 | 58% | 11% | [28] |
Cytarabine 100 mg/m2 CI days 1–8 | ||||
Etoposide 100–120 mg/m2 days 4–8 | ||||
FLAD | Fludarabine 30 mg/m2 days 1–3 | 53% | 7.5% | [29] |
Cytarabine 2 g/m2 days 1–3 | ||||
Liposomal daunorubicin 100 mg/m2 days 1–3 | ||||
FLAM | Flavopiridol 50 mg/m2 days 1–3 | 28%–43% | 5%–28% | [30,31] |
Cytarabine 2 g/m2/72 h starting day 6 | ||||
Mitoxantrone 40 mg/m2 day 9 | ||||
Hybrid FLAM | Flavopiridol 30mg/m2 bolus, 60 mg/m2 over 4 h days 1–3 | 40% | 9% | [32] |
Cytarabine 2 g/m2/72 h starting day 6 | ||||
Mitoxantrone 40 mg/m2 day 9 | ||||
Clofarabine Cytarabine | Clofarabine 40 mg/m2 days 2–6 | 28%–51% | 6.2%–13% | [33] |
Cytarabine 1 g/m2 days 1–5 | ||||
Clofarabine 40 mg/m2 days 1–5; Cytarabine 1 g/m2 days 1–5 | [34,35] | |||
Clofarabine 22.5 mg/m2 days 1–5; Cytarabine 1 g/m2 days 1–5 | ||||
GCLAC | Clofarabine 25 mg/m2 days 1–5; Cytarabine 2 g/m2 days 1–5; G-CSF 5 mcg/kg day 0 until ANC recovery | 46%, (CR + CRp 61%) | 13% | [36,37] |
HAA | Homoharringtonine 4 mg/m2 days 1–3 | 76%–80% | 0% | [38] |
Cytarabine 150 mg/m2 days 1–7 | ||||
Aclarubicin 12 mg/m2 days 1–7 | ||||
CPX 351 | CPX 351 101 units/m2 days 1, 3, and 5 | 23%–37% (CR + CRi = 49%) | 7%–13% | [39] |
CPX 351 100 units/m2 days 1, 3, 5 (first induction) and days 1 and 3 (second induction and consolidation) | [40] |
Agent | Mechanism of Action | Ongoing Clinical Trial | Reference |
---|---|---|---|
Ruxolitinib | JAK1 and JAK2 inhibitor | NCT02257138, NCT00674479, NCT01251965 | [41,42] |
Rapamycin | mTOR inhibitor | NCT01184898, NCT01869114, NCT00634244, NCT02109744 | [43,44] |
Everolimus | mTOR inhibitor | NCT00819546 | [45] |
Tosedostat | Aminopeptidase activity inhibitor | NCT01636609 | [46,47] |
Vorinostat | Histone deacetylase inhibitor | NCT01130506, NCT01534260, NCT01550224, NCT01617226, NCT02083250 | [48,49,50] |
AG-120 | IDH1 inhibitor | NCT02074839 | NCT02074839 |
AG-221 | IDH2 inhibitor | NCT01915498 | [51] |
Elacytarabine | Elaidic acid ester of cytarabine | No active studies found | [52] |
Vosaroxin | Anticancer quinolone derivative | NCT01191801 | [53,54] |
Pravastatin | HMG-CoA reductase inhibitor | NCT00840177 | [55,56] |
Bortezomib | Proteasome inhibitor | NCT01174888, NCT01127009, NCT01736943, NCT01861314, NCT01534260, NCT01075425, NCT00410423 | [57] |
Lenalidomide | Immunomodulatory agent | NCT01681537, NCT01904643, NCT01629082, NCT01132586, NCT01246622, NCT01743859, NCT01016600, NCT00466895, NCT01615042 | [58] |
CPI-613 | Lipoate derivative | NCT01768897 | [59] |
ABT-199 | BCL-2 inhibitor | NCT01994837 | [60] |
Erismodegib | Hedgehog inhibitor | NCT02129101 | NCT02129101 |
PF-04449913 | Hedgehog inhibitor | NCT02038777 | NCT02038777 |
Agent | Mechanism of Action | Ongoing Clinical Trial | Reference |
---|---|---|---|
Gemtuzumab ozogamicin | Conjugated Antibody targeting CD33 | NCT01869803, NCT00766116, NCT02221310 | [61,62,63] |
SGN-CD33A | Conjugated Antibody targeting CD33 | NCT01902329 | [64,65] |
Lintuzumab | Unconjugated Antibody targeting CD33 | No active studies found | [66] |
CSL362 | Unconjugated Antibody targeting CD123 | No active studies found | [67,68] |
AMG330 | Bispecific T-cell Engaging Antibody targeting CD33 and CD3 | No active studies found | [69,70] |
MGD006 | Dual Affinity Re-Targeting Antibody targeting CD123 and CD3 | NCT02152956 | [71] |
CD16x33 BiKE | Bispecific Killer Cell Engager Antibody against CD16 and CD33 | No active studies found | [72] |
CART33 | Chimeric Antigen Receptor-Transduced T Cells targeting CD33 | NCT01864902 | [73] |
CART123 | Chimeric Antigen Receptor-Transduced T Cells targeting CD123 | NCT02159495 | [74,75] |
WT1 peptide vaccine | Vaccine targeting WT1 | NCT00965224 | [76,77] |
WT1-specific CD8(+) T-cell infusion | Adoptive Cell Transfer | NCT01640301 | [78,79,80] |
Haploidentical NK cell infusion | Adoptive Cell Transfer | NCT01947322, NCT01385423, NCT01370213, NCT00303667, NCT01621477, NCT00526292, NCT00789776, NCT02259348, NCT01795378, NCT01898793, NCT01386619 | [81] |
AlloHSCT | Adoptive Cell Transfer | More than 40 active clinical trials identified | [82,83,84,85] |
Donor lymphocyte infusion (post alloHCT) | Adoptive Cell Transfer | NCT01758367, NCT01390311, NCT00068718, NCT01523223, NCT01760655, NCT00534118, NCT00005799, NCT00448357 | [86,87,88,89] |
3. Targeted Agents
4. Immunotherapy
5. Low-Intensity Therapy
6. Discussion
7. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Ramos, N.R.; Mo, C.C.; Karp, J.E.; Hourigan, C.S. Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia. J. Clin. Med. 2015, 4, 665-695. https://doi.org/10.3390/jcm4040665
Ramos NR, Mo CC, Karp JE, Hourigan CS. Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia. Journal of Clinical Medicine. 2015; 4(4):665-695. https://doi.org/10.3390/jcm4040665
Chicago/Turabian StyleRamos, Nestor R., Clifton C. Mo, Judith E. Karp, and Christopher S. Hourigan. 2015. "Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia" Journal of Clinical Medicine 4, no. 4: 665-695. https://doi.org/10.3390/jcm4040665