New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes
Abstract
:1. Introduction
2. Immune System Dysfunction in AML/MDS
3. Immune System Regulators
3.1. CD47
3.2. Immune Checkpoint Regulators
3.2.1. CTLA-4
3.2.2. PD-1/PD-L1
3.2.3. TIM-3
3.3. TLR-2
4. Other Molecular Targets on the AML/MDS Cell Membrane
4.1. CD33
4.2. CD123
4.3. CD45
4.4. CD70
5. Target Immunotherapies in AML
5.1. Targeting CD47
5.2. Immune Checkpoint Inhibitors
5.3. Targeting CD33
5.4. Targeting CD123
5.5. Targeting CD45
5.6. Targeting CD70
6. Target Immunotherapies in MDS
6.1. Targeting CD47
6.2. Immune Checkpoint Inhibitors
6.3. Targeting TLR-2
6.4. Targeting CD33
6.5. Targeting CD123
7. Conclusions and Perspectives
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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NCT Code | Trial | Target | Study Population | Efficacy Results | Ref. |
---|---|---|---|---|---|
NCT03248479 | Ongoing phase Ib, magrolimab + AZA | CD47 | untreated AML unfit for induction chemotherapy. | ORR 69%: 50% CR or CRi, 13% PR and 31% SD | [18] |
NCT02678338 | Phase I, magrolimab | CD47 | R/R AML | N/A | [19] |
NCT04755244 | Ongoing phase I/II, evorpacept + venetoclax + AZA | CD47 | R/R AML ineligible for standard induction chemotherapy | N/A | N/A |
NCT01822509 | Phase I/Ib, ipilimumab | CTLA-4 | R/R AML after allogeneic HSCT | Durable response (>1 year): 4/22 | [20] |
NCT02397720 | Ongoing phase II, nivolumab + AZA | PD-1 | R/R AML | ORR: 33% mOS: 10.6 months | [21] |
NCT02530463 | Ongoing phase II, ipilimumab + nivolumab + AZA vs. nivolumab + AZA vs. AZA | PD-1 | R/R AML | Ipilimumab + nivolumab + AZA arm: mOS 7.6 months; Nivolumab + AZA arm: mOS 5.9 months; AZA control arm: mOS 4.4 months | [22] |
NCT03066648 | Phase Ib, sabatolimab +/− PDR001 + HMA | TIM-3 | AML | ND AML unsuitable for induction chemotherapy: ORR 41.2%, CR 8%, CRi 3%, PR 3% | [23] |
NCT02785900 | Phase III, vadastuximab talirine + AZA/decitabine vs. placebo | CD33 | Older ND AML | Terminated (due to poor safety) | [24,25] |
NCT02575963 | Phase II, 225 Ac-lintuzumab | CD33 | AML | 69% remission | [26] |
NCT02520427 | Ongoing phase I, AMG330 | CD33 | R/R AML | CR/CRi 11.4% | [27] |
NCT03647800 | Phase IB, APVO436 | CD123 | R/R AML | N/A | [28] |
NCT02730312 | Ongoing phase I, vibecotamab | CD123 | R/R AML | CR/CRi: 23% | [29] |
NCT03386513 | Ongoing phase I/II, IMGN632 | CD123 | R/R AML | CR: 1/12, CRi: 3/12 | [30] |
NCT03113643 | Ongoing phase I, tagraxofusp + AZA vs. AZA/venetoclax | CD123 | AML | N/A | [31] |
NCT02152956 | Ongoing phase I/II, flotetuzumab | CD123 | R/R AML | ORR 13.6%, CR 11.7% | [32] |
NCT00008177 | Phase I, iomab-B + FLU + 2 Gy TBI | CD45 | Over 50 years AML | N/A | [33] |
NCT02665065 | Ongoing phase III, iomab-B + FLU + low-dose TBI | CD45 | R/R AML | N/A | [33] |
NCT01300572 | Phase I, 90Y-BC8 + FLU/TBI | CD45 | AML ineligible for allogeneic HSCT | OS at 1.8 years: 53% | [34] |
NCT03030612 | Phase I/II, cusatuzumab monotherapy followed by cusatuzumab + AZA | CD70 | Untreated older AML | CR/CRi: 83% | [35] |
NCT Code | Trial | Target | Study Population | Efficacy Results | Ref. |
---|---|---|---|---|---|
NCT03248479 | Ongoing phase Ib, magrolimab + AZA | CD47 | treatment-naïve MDS from intermediate to very high | ORR 91%: CR 42%, mCR 24%; PR 3% | [36] |
NCT04313881 | Ongoing phase III, magrolimab + AZA vs. AZA + placebo | CD47 | Treatment-naïve HR-MDS | NA | N/A |
NCT04417517 | Ongoing phase I/II, evorpacept + AZA | CD47 | R/R or ND HR-MDS | mCR: 3/10; cytogenic response: 2/10 SD: 2/10 | [37] |
NCT02530463 | Ongoing phase II, ipilimumab and/or nivolumab +/− AZA | CTLA-4 | HMA-failure MDS or untreated MDS | HMA-failure arm: ORR 36%, CR 9%, CRi 9%, mOS 11.4 months; frontline arm: ORR 67%, CR 33%, mOS 12% | [38] |
NCT03094637 | Ongoing phase II, pembrolizumab + AZA | PD-1 | HMA-failure or untreated INT1 or HR-MDS | HMA-failure arm: ORR 25%; frontline arm: ORR 76%, CR 18%, mCR 29% | [39] |
NCT03066648 | Ongoing phase Ib, sabatolimab + HMA | TIM-3 | High risk and very high risk MDS | ORR 56.9%, mDOR: 16.1 months | [40] |
NCT02363491 | Ongoing phase I/II, tomaralimab | TLR-2 | HMA-failure and transfusion-dependent LR-MDS patients | ORR: 50% | [41] |
NCT03337451 | Ongoing phase I/II, tomaralimab | TLR-2 | HMA-failure and transfusion-dependent LR-MDS patients | ORR: 50% | [42] |
NCT03214666 | Phase I/II, GTB-3550 | CD33 | HR-MDS | N/A | [43] |
NCT03647800 | Ongoing Ib, APVO436 | CD123 | R/R MDS after HMA-failure | mCR: 50% | [28] |
NCT03113643 | Ongoing phase Ib, tagraxofusp + AZA | CD123 | MDS | CR 50%, mCR: 25% | [44] |
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Gallazzi, M.; Ucciero, M.A.M.; Faraci, D.G.; Mahmoud, A.M.; Al Essa, W.; Gaidano, G.; Mouhssine, S.; Crisà, E. New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes. Int. J. Mol. Sci. 2022, 23, 7542. https://doi.org/10.3390/ijms23147542
Gallazzi M, Ucciero MAM, Faraci DG, Mahmoud AM, Al Essa W, Gaidano G, Mouhssine S, Crisà E. New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes. International Journal of Molecular Sciences. 2022; 23(14):7542. https://doi.org/10.3390/ijms23147542
Chicago/Turabian StyleGallazzi, Marco, Maghalie Anais Marie Ucciero, Danilo Giuseppe Faraci, Abdurraouf Mokhtar Mahmoud, Wael Al Essa, Gianluca Gaidano, Samir Mouhssine, and Elena Crisà. 2022. "New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes" International Journal of Molecular Sciences 23, no. 14: 7542. https://doi.org/10.3390/ijms23147542