Selected studies of posttransplant maintenance therapy
| Lead Author . | Year Journal . | Disease . | Therapy . | Study information . | Main clinical outcome . | Secondary clinical outcome . | Subgroup analysis . | Main clinical outcome in subgroup . | Toxicity . | Miscellaneous . |
|---|---|---|---|---|---|---|---|---|---|---|
| Targeted therapy | ||||||||||
| Levis4 | 2024 JCO | FLT3-ITD AML | Gilteritinib 120 mg × 2 y | RCT glt vs placebo, n = 356 | RFS HR 0.68, P = 0.052 | MRD+ before or after HCT | RFS HR 0.5, P = 0.0065 favoring MRD+ (no benefit in MRD−) | |||
| Brissot8 | 2015 Haematologica | ALL Ph+ | TKI pretransplant and/or posttransplant | Retrospective n = 473 ALL Ph+ CR1 who underwent alloSCT n = 157 TKI after transplant | Posttransplant TKI maintenance showed benefits in leukemia-free survival (HR = 0.44; P = 0.002), overall survival (HR = 0.42; P = 0.004), and a lower relapse incidence (HR = 0.40; P = 0.01). | |||||
| Guan69 | 2024 Cancer | ALL Ph+ | Imatinib Dasatinib | Retrospective, n = 91 imatinib, n = 50 dasatinib | 5 y imat vs dasat CIR 16% vs 12% NRM 5% vs 9.8% OS 86% vs 78% | Mild GVHD higher in dasatinib | Neutropenia GI bleed in dasatinib | |||
| Fathi5 | 2023 Clin Cancer Res | IDH1 AML | Ivosidenib × 12 cycles – RP2D 500 mg daily | Phase 1, n = 18 (16 got ivo) | 2 y CIR 19% 2 y NRM 0% 2 y PFS 81% 2 y OS 88% | 6 m aGVHD 6% g2-4 | QTc prolongation in n = 2 | N = 8 stopped maintenance | ||
| Fatchi6 | 2022 Blood Adv | IDH2 AML | Enasidenib | Phase 1, n = 23 | 2 y CIR 16% 2 y PFS 69% 2 y OS 74% | 6 m aGVHD 16% g2-4, 12 m cGVHD 42% mod/sev | Neutropenia, anemia | N = 8 stopped maintenance | ||
| Cheng70 | 2024 Transplant Immunol | ALL | Ruxolitinib 5-10 mg BID | Observational, n = 8 | Relapse in 25% at 14 m f/u | aGVHD: 25% gr1-2, 0 gr3-4, 12% cGVHD | ||||
| Maintenance chemotherapy | ||||||||||
| Garcia13 | 2024 Blood Adv | MDS/AML | Aza 36 m/m2 D1-5 + ven 400 mg D1-14 × 8 42 d cycles or 12 28 d cycles | Phase 1, n = 27 96% MRD+ | mOS NR at 25 m f/u | n = 22 who got ven/aza | 2 y OS 67%, PFS 59%, NRM 0%, CIR 41% | Leukopenia, neutropenia, thrombocytopenia | ||
| Fan71 | 2023 BMT | ALL | Decitabine | Retrospective, n = 65 decitabine, n = 76 control | 3 y CIR 19.6% decitabine vs 36% control, HR 0.49 | T-ALL 3 y CIR 11.7 vs. 35.9% favoring decitabine Ph- B-ALL 3 yCIR 19 vs 42% favoring decitabine | ||||
| Kent12 | 2023 BMT | AML | Ven × 1 y after HCT | Prospective, n = 49 | 1 y OS 70% | 1 y RFS 67% | Cytopenias, GI | 88% completed full year, 67% had dose interruptions | ||
| Pasvolsky10 | 2024 Clin Lympoma Myeloma Leuk | AML FLT3-neg/MDS | Aza | Retrospective matched control, n = 93 Aza, n = 257, control | 3 y CIR 29% vs 33% P = 0.09 | High risk AML/MDS | HR 0.4 CIR, P = 0.009 favoring Aza; PFS HR 0.2, P = 0.004; and AML HR 0.4, P = 0.04 | |||
| Pharmacological immunotherapy | ||||||||||
| Metheny14 | 2024 Blood Adv | ALL Ph+ | Inotuzumab – 0.6 mg/m2 identified as MTD | Phase 1, high risk of recurrence, n = 19 | 1 y nonrelapse mortality 5.6% | PFS 89% and OS 94% at 1 y with 18 m f/u | Thrombocytopenia, no VOD | |||
| Adoptive cell immunotherapy | ||||||||||
| Chapuis66 | 2019 Nat Med | AML | Wilms' Tumor Antigen 1-specific TCR transduced Epstein-Bar virus-specific donor CD8 T cells (TTCR-C4) | Phase 1 prophylactic infusion n = 12 | 3 y RFS 100%, compared to control group 54% (P = 0.002) | 1 patient developed grade 3 acute GVHD. No differences in the incidences of chronic GVHD compared to comparative control group (55% vs 61%) | ||||
| Lulla67 | 2021 Blood | AML/MDS | Donor-derived mLST | Phase 1 Adjuvant arm n = 17 (n = 12, prophylactic infusion for the patients who never relapsed after HSCT, n = 5 relapsed after HSCT but in CR after salvage therapy) | 11/17 never relapsed after mLST infusion. Median LFS not reached. | 2-year OS 77% | No grade 2 or above GVHD, or no extensive chronic GVHD | |||
| Lead Author . | Year Journal . | Disease . | Therapy . | Study information . | Main clinical outcome . | Secondary clinical outcome . | Subgroup analysis . | Main clinical outcome in subgroup . | Toxicity . | Miscellaneous . |
|---|---|---|---|---|---|---|---|---|---|---|
| Targeted therapy | ||||||||||
| Levis4 | 2024 JCO | FLT3-ITD AML | Gilteritinib 120 mg × 2 y | RCT glt vs placebo, n = 356 | RFS HR 0.68, P = 0.052 | MRD+ before or after HCT | RFS HR 0.5, P = 0.0065 favoring MRD+ (no benefit in MRD−) | |||
| Brissot8 | 2015 Haematologica | ALL Ph+ | TKI pretransplant and/or posttransplant | Retrospective n = 473 ALL Ph+ CR1 who underwent alloSCT n = 157 TKI after transplant | Posttransplant TKI maintenance showed benefits in leukemia-free survival (HR = 0.44; P = 0.002), overall survival (HR = 0.42; P = 0.004), and a lower relapse incidence (HR = 0.40; P = 0.01). | |||||
| Guan69 | 2024 Cancer | ALL Ph+ | Imatinib Dasatinib | Retrospective, n = 91 imatinib, n = 50 dasatinib | 5 y imat vs dasat CIR 16% vs 12% NRM 5% vs 9.8% OS 86% vs 78% | Mild GVHD higher in dasatinib | Neutropenia GI bleed in dasatinib | |||
| Fathi5 | 2023 Clin Cancer Res | IDH1 AML | Ivosidenib × 12 cycles – RP2D 500 mg daily | Phase 1, n = 18 (16 got ivo) | 2 y CIR 19% 2 y NRM 0% 2 y PFS 81% 2 y OS 88% | 6 m aGVHD 6% g2-4 | QTc prolongation in n = 2 | N = 8 stopped maintenance | ||
| Fatchi6 | 2022 Blood Adv | IDH2 AML | Enasidenib | Phase 1, n = 23 | 2 y CIR 16% 2 y PFS 69% 2 y OS 74% | 6 m aGVHD 16% g2-4, 12 m cGVHD 42% mod/sev | Neutropenia, anemia | N = 8 stopped maintenance | ||
| Cheng70 | 2024 Transplant Immunol | ALL | Ruxolitinib 5-10 mg BID | Observational, n = 8 | Relapse in 25% at 14 m f/u | aGVHD: 25% gr1-2, 0 gr3-4, 12% cGVHD | ||||
| Maintenance chemotherapy | ||||||||||
| Garcia13 | 2024 Blood Adv | MDS/AML | Aza 36 m/m2 D1-5 + ven 400 mg D1-14 × 8 42 d cycles or 12 28 d cycles | Phase 1, n = 27 96% MRD+ | mOS NR at 25 m f/u | n = 22 who got ven/aza | 2 y OS 67%, PFS 59%, NRM 0%, CIR 41% | Leukopenia, neutropenia, thrombocytopenia | ||
| Fan71 | 2023 BMT | ALL | Decitabine | Retrospective, n = 65 decitabine, n = 76 control | 3 y CIR 19.6% decitabine vs 36% control, HR 0.49 | T-ALL 3 y CIR 11.7 vs. 35.9% favoring decitabine Ph- B-ALL 3 yCIR 19 vs 42% favoring decitabine | ||||
| Kent12 | 2023 BMT | AML | Ven × 1 y after HCT | Prospective, n = 49 | 1 y OS 70% | 1 y RFS 67% | Cytopenias, GI | 88% completed full year, 67% had dose interruptions | ||
| Pasvolsky10 | 2024 Clin Lympoma Myeloma Leuk | AML FLT3-neg/MDS | Aza | Retrospective matched control, n = 93 Aza, n = 257, control | 3 y CIR 29% vs 33% P = 0.09 | High risk AML/MDS | HR 0.4 CIR, P = 0.009 favoring Aza; PFS HR 0.2, P = 0.004; and AML HR 0.4, P = 0.04 | |||
| Pharmacological immunotherapy | ||||||||||
| Metheny14 | 2024 Blood Adv | ALL Ph+ | Inotuzumab – 0.6 mg/m2 identified as MTD | Phase 1, high risk of recurrence, n = 19 | 1 y nonrelapse mortality 5.6% | PFS 89% and OS 94% at 1 y with 18 m f/u | Thrombocytopenia, no VOD | |||
| Adoptive cell immunotherapy | ||||||||||
| Chapuis66 | 2019 Nat Med | AML | Wilms' Tumor Antigen 1-specific TCR transduced Epstein-Bar virus-specific donor CD8 T cells (TTCR-C4) | Phase 1 prophylactic infusion n = 12 | 3 y RFS 100%, compared to control group 54% (P = 0.002) | 1 patient developed grade 3 acute GVHD. No differences in the incidences of chronic GVHD compared to comparative control group (55% vs 61%) | ||||
| Lulla67 | 2021 Blood | AML/MDS | Donor-derived mLST | Phase 1 Adjuvant arm n = 17 (n = 12, prophylactic infusion for the patients who never relapsed after HSCT, n = 5 relapsed after HSCT but in CR after salvage therapy) | 11/17 never relapsed after mLST infusion. Median LFS not reached. | 2-year OS 77% | No grade 2 or above GVHD, or no extensive chronic GVHD | |||
Aza, azacitinide; cGVHD, chronic GVHD; CR1, first complete remission; GI, gastrointestinal; LFS, leukemia-free survival; mLST, multiple leukemia antigen–specific T cells; mOS, median overall survival; MTD, maximum tolerated dose; NR, not reached; R2PD, recommended phase 2 dose; T-ALL, T-cell acute lymphoblastic leukemia.