Changing Landscape in the Treatment of Adult Acute Lymphoblastic Leukemia (ALL)
Abstract
:Simple Summary
Abstract
1. Introduction
2. Epidemiology, Clinical Presentation
3. Diagnostic, Genetic and Prognostic Factors
4. Measurable Residual Disease (MRD) Monitoring
5. First-Line Therapy of Acute Lymphoblastic Leukemia
6. CNS Prophylaxis
7. Antibody-Based Therapy
7.1. Monotherapy with Blinatumomab in Relapsed/Refractory ALL
7.2. Monotherapy with Inotuzumab Ozogamicin in Relapsed/Refractory ALL
7.3. Chemoimmunotherapy
7.4. Chemoimmunotherapy with Inotuzumab Ozogamicin in Relapsed/Refractory ALL
7.5. Chemoimmunotherapy with Blinatumomab in Newly Diagnosed B-Cell ALL
7.6. Chemoimmunotherapy with Rituximab
7.7. Chemoimmunotherapy with Ofatumumab
7.8. Chemoimmunotherapy with Epratuzumab
8. Therapy Opportunities for Older Adults
Regimen | Study Population | N | Median Age | CR/CRi Rate | CR Duration | MRD- Negativity | OS Rate | Reference |
---|---|---|---|---|---|---|---|---|
Inotuzumab + mini-HCVD ± blinatumomab | Patients aged ≥60 years | 64 | 68 | 98% | 76% (3-year) | 95% | 54% (3-year) | [37] |
Blinatumomab + POMP | Patients aged >60 years | 31 | 73 | 66% | DFS 56% (1-year) | 92% | 65% (1-year) | [38] |
9. Therapy of T-ALL
10. Therapy of Philadelphia Chromosome-Positive ALL
11. Chimeric Antigen Receptor (CAR) T Cell Therapy
12. Hematopoietic Stem Cell Transplantation
13. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Subgroup | Immunophenotype | Cytogenetic, Molecular Genetics |
---|---|---|
B-Lineage ALL | HLA-DR+, TdT+/−, CD19+, cyCD79a+, cyCD22+ | |
Pro-B-ALL | CD10- | t(v;11), KMT2A rearrangements |
c-common-ALL | CD10+ | t(9;22), BCR::ABL1; IKZF1 |
Premature B-ALL | cyIgM+ | t(1;19)TCF3::PBX1; t(9;22); BCR::ABL1 IKZF1 |
Mature B-ALL | TdT−, CD34−, sIg+ | t(8;14); MYC rearrangements |
T-lineage ALL | TdT+/−, cyCD3+, CD7+ | |
Pro-T-ALL | cCD3+, sCD3−, CD1a−, CD2+, CD5−, CD7+, CD34− | NOTCH1/FBXW7 mutations |
Pre-T/immature T-ALL | cCD3+, sCD3−, CD1a−, CD2+, CD5+, CD7+, CD34− | NOTCH1/FBXW7 mutations, HOXA, TLX3 |
Cortical T-ALL | cCD3+, sCD3+/−, CD1a+, CD2+, CD5+, CD7+, CD34− | NOTCH1/FBXW7 mutations, TLX1, NKX2.1./2.2, TLX3, TAL/LMO |
Early T-cell precursor ALL | cCD3+, sCD3−, CD1a−, CD2+, CD7+, HLA-DR, CD13, CD33, CD34, CD117 | NOTCH1/FBXW7 mutations, HOXA, MEF2C, BCL11B |
Mature T-ALL | cCD3+, sCD3+, CD1a−, CD2+, CD5+, CD7+, CD34− | NOTCH1/FBXW7 mutations, TAL/LMO |
Therapy | Target | Antibody Type |
---|---|---|
Blinatumomab | CD19 | BiTE |
Inotuzumab ozogamicin | CD22 | ADC |
Rituximab | CD20 | mAb |
Ofatumumab | CD20 | mAb |
Epratuzumab | CD22 | mAb |
Regimen | Indication | N | Median Age | CR/CRi Rate | CR Duration | MRD-Negativity | OS Rate | Reference |
---|---|---|---|---|---|---|---|---|
Inotuzumab + mini-HCVD ± blinatumomab | R/R ALL | 84 | 35 | 80% | 52% (2-year) | 80% | 39% (2-year) | [26] |
Inotuzumab + CVP | R/R CD22+ ALL | 48 | 43 | 61% | / | / | 10.9 months (median) | [27] |
Hyper-CVAD + blinatumomab | Newly diagnosed B-ALL | 27 | 38 | 100% | RFS 76 % | 96% | 89% (1-year) | [28] |
Hyper-CVAD + rituximab | CD20+, ALL | 209 | 40 | 92% | / | 91% | EFS (2-year) 65% | [29] |
Standard/ modified Hyper-CVAD + rituximab | B-ALL | 282 | 41 | 95% | 78% | 81% | 60% (3-year) | [30] |
Hyper-CVAD + rituximab | Newly diagnosed B-ALL | 31 | 46 | 86% | 67% (3-year) | / | 89% | [31] |
Hyper-CVAD + MTX + cytarabine+ ofatumumab | Newly diagnosed CD20+, B-ALL | 69 | 41 | 98% | / | 65% | 68% (4-year) | [32] |
Hyper-CVAD + ofatumumab | Newly diagnosed CD20+ B-ALL | 222 | 44 | 93% | / | 93% | 66% (4-year) | [33] |
Regimen | Study Population | N | Median Age | CR Rate | HSCT Rate | EFS | RFS | OS Rate | Reference |
---|---|---|---|---|---|---|---|---|---|
Imatinib + hyper-CVAD | Newly diagnosed Ph + ALL | 54 | 51 | 93% | 30% | 43% (5-year) | 43% (5-year) | 43% (5-year) | [49] |
Imatinib + intensive chemotherapy | Newly diagnosed Ph + ALL (age 15–65) | 266 | 42 | 92% | 72% | 33% (4-year) | 50% (4-year) | 38% (4-year) | [50] |
Imatinib + lower-intensity chemotherapy | 268 | 49 | 98% | 62% | 37.1% (5-year) | EFS 37% (5-year) | 46% (5-year) | [51] |
Regimen | Study Population | N | Median Age | CR Rate | HSCT Rate | EFS | RFS | OS Rate | Reference |
---|---|---|---|---|---|---|---|---|---|
Dasatinib + intensive chemotherapy | Ph + ALL | 72 | 55 | 96% | 17% | 27 months (median) | 44% (5-year) | 46% (5-year) | [52] |
Dasatinib + lower-intensity chemotherapy | Ph + ALL | 71 | 69 | 96% | 10% | 27% (5-year) | EFS 28% (5-year) | 36% (5-year) | [53] |
Dasatinib + lower-intensity chemotherapy | Ph + ALL | 60 | 42 | 100% | 42% | 48% (5-year) | 49% (3-year) | 58% (3-year) | [54] |
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Künz, T.; Hauswirth, A.W.; Hetzenauer, G.; Rudzki, J.; Nachbaur, D.; Steiner, N. Changing Landscape in the Treatment of Adult Acute Lymphoblastic Leukemia (ALL). Cancers 2022, 14, 4290. https://doi.org/10.3390/cancers14174290
Künz T, Hauswirth AW, Hetzenauer G, Rudzki J, Nachbaur D, Steiner N. Changing Landscape in the Treatment of Adult Acute Lymphoblastic Leukemia (ALL). Cancers. 2022; 14(17):4290. https://doi.org/10.3390/cancers14174290
Chicago/Turabian StyleKünz, Tina, Alexander W. Hauswirth, Gabriele Hetzenauer, Jakob Rudzki, David Nachbaur, and Normann Steiner. 2022. "Changing Landscape in the Treatment of Adult Acute Lymphoblastic Leukemia (ALL)" Cancers 14, no. 17: 4290. https://doi.org/10.3390/cancers14174290