Therapeutic combination strategies developed using autophagy modulators in hematopoietic diseases
| Disease . | Therapy . | Effects of autophagy induction . | Combination strategy . | Effect of combination . | Clinical trial . | Clinical trial reference . |
|---|---|---|---|---|---|---|
| AML | Cytarabine | Cytoprotection/chemoresistance | Bafilomycin A1 | Enhanced cytotoxicity | No | |
| Chloroquine | ||||||
| Mitoxantrone + Etoposide | Unknown | Hydroxychloroquine | Unknown | Phase 1 | NCT02631252 | |
| Statins | Cytoprotection | Bafilomycin A1 | Enhanced cytotoxicity | No | ||
| Recombinant human arginase | Unknown | 3-Methyladenine | Enhanced cytotoxicity | No | ||
| Chloroquine | ||||||
| CML | Imatinib | Unknown | Chloroquine | Enhanced cytotoxicity | No | |
| Hydroxychloroquine | Unknown | Phase 2 | NCT01227135 | |||
| T-ALL | Recombinant human arginase | Unknown | 3-Methyladenine | Enhanced cytotoxicity | No | |
| Chloroquine | ||||||
| Dexamethasone | Chemoresistance | Chloroquine | Overcome resistance | No | ||
| 3-Methyladenine | ||||||
| B-cell disorders | Chlorambucil-coupled anti-CD20 antibody | Unknown | Hydroxychloroquine | Enhanced cytotoxicity | No | |
| Bortezomib | Unknown | 3-Methyladenine | Enhanced cytotoxicity | No | ||
| Chloroquine | ||||||
| Multiple myeloma | Bortezomib | Cytoprotection/chemoresistance | Metformin | Enhanced cytotoxicity | No | |
| Hydroxychloroquine | Phase 1/2 | NCT00568880 | ||||
| Cyclophosphamide/dexamethasone/sirolimus | Unknown | Hydroxychloroquine | Enhanced cytotoxicity | Phase 1 | NCT01689987 |
| Disease . | Therapy . | Effects of autophagy induction . | Combination strategy . | Effect of combination . | Clinical trial . | Clinical trial reference . |
|---|---|---|---|---|---|---|
| AML | Cytarabine | Cytoprotection/chemoresistance | Bafilomycin A1 | Enhanced cytotoxicity | No | |
| Chloroquine | ||||||
| Mitoxantrone + Etoposide | Unknown | Hydroxychloroquine | Unknown | Phase 1 | NCT02631252 | |
| Statins | Cytoprotection | Bafilomycin A1 | Enhanced cytotoxicity | No | ||
| Recombinant human arginase | Unknown | 3-Methyladenine | Enhanced cytotoxicity | No | ||
| Chloroquine | ||||||
| CML | Imatinib | Unknown | Chloroquine | Enhanced cytotoxicity | No | |
| Hydroxychloroquine | Unknown | Phase 2 | NCT01227135 | |||
| T-ALL | Recombinant human arginase | Unknown | 3-Methyladenine | Enhanced cytotoxicity | No | |
| Chloroquine | ||||||
| Dexamethasone | Chemoresistance | Chloroquine | Overcome resistance | No | ||
| 3-Methyladenine | ||||||
| B-cell disorders | Chlorambucil-coupled anti-CD20 antibody | Unknown | Hydroxychloroquine | Enhanced cytotoxicity | No | |
| Bortezomib | Unknown | 3-Methyladenine | Enhanced cytotoxicity | No | ||
| Chloroquine | ||||||
| Multiple myeloma | Bortezomib | Cytoprotection/chemoresistance | Metformin | Enhanced cytotoxicity | No | |
| Hydroxychloroquine | Phase 1/2 | NCT00568880 | ||||
| Cyclophosphamide/dexamethasone/sirolimus | Unknown | Hydroxychloroquine | Enhanced cytotoxicity | Phase 1 | NCT01689987 |
The table represents different therapeutic strategies combining front-line therapies and autophagy inhibitors that have been used in various hematopoietic disorders. Some of them are currently being tested in the clinical trials referenced in this table.