Prophylactic or Preemptive Low-Dose Azacitidine and Donor Lymphocyte Infusion to Prevent Disease Relapse following Allogeneic Transplantation in Patients with High-Risk Acute Myelogenous Leukemia or Myelodysplastic Syndrome

Guillaume, Thierry; Thépot, Sylvain; Péterlin, Pierre; Céballos, Patrice; Bourgeois, Amandine Le; Garnier, Alice; Orvain, Corentin; Giltat, Aurélien; François, Sylvie; Bris, Yannick Le; Fronteau, Clémentine; Planche, Lucie; Chevallier, Patrice

doi:10.1016/j.jtct.2021.06.029

Cited by 26 publications

(16 citation statements)

References 38 publications

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“…Meanwhile, the 2-year CI of grade I-III aGVHD was 31.5% (36). In another retrospective study analyzing 77 high-risk AML/MDS patients based on unfavorable genomic or clinical status at transplantation (AML, n = 54; MDS, n = 23), prophylactic or pre-emptive azacitidine combined with DLI achieved a 2-year CI of relapse of 22%, and the CIs of grade II-IV acute GVHD and cGVHD were 27.4 and 45%, respectively (77).…”

Section: New Drugs and DLI Hypomethylating Agentsmentioning

confidence: 98%

“…In the trial conducted by Jedlickova et al testing prophylactic DLI for high-risk AML after allo-HCT, only ~30% of patients received prophylactic DLI as planned in the protocol (37), while in another phase II trial on prophylactic azacytidine + DLI for high-risk AML/MDS after allo-HCT, 56.7% of patients received at least one DLI (36). In the retrospective study conducted by Guillaume et al evaluating the efficacy of prophylactic/preemptive azacytidine + DLI on high-risk AML/MDS after allo-HCT, 79% of patients received at least one DLI (77). For therapeutic DLI, inadequate organ function, active severe acute/chronic GVHD, and severe infections are regarded as contraindications (24).…”

Section: Feasibility and Side Effects Of DLImentioning

confidence: 99%

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Optimization of Donor Lymphocyte Infusion for AML Relapse After Allo-HCT in the Era of New Drugs and Cell Engineering

Yang

Yuan

et al. 2022

Front. Oncol.

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Donor lymphocyte infusion (DLI) is a key strategy for the treatment of AML relapse after allogeneic hematopoietic cell transplantation (allo-HCT) and has been used for either prophylactic, pre-emptive, or therapeutic purposes. However, the prognosis of these patients remains dismal even after DLI infusion (2-year overall survival, ~25%), and the efficacy is achieved at the cost of toxicities such as graft-versus-host (GVH) disease. Attempts to optimize DLI efficacy and safety, such as dose/timing modification and the use of cytoreduction, before DLI have been performed previously. Recently, a great number of novel targeted and immunomodulatory agents have emerged. Some of them, such as hypomethylating agents, FLT3 and Bcl-2 inhibitors, have been used in combination with DLI, aiming to enhance the graft-versus-leukemia effect. Moreover, manipulation of the DLI graft through cell selection (e.g., donor NK cells) or cell engineering (donor CAR-T cells) has shown potentially superior anti-tumor effects but less GVH effect than conventional DLI in clinical trials. This review summarizes the recent advances on the use of DLI for the prophylaxis/treatment of AML relapse and discusses future strategies which may further improve the treatment efficacy.

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Section: New Drugs and DLI Hypomethylating Agentsmentioning

confidence: 98%

Section: Feasibility and Side Effects Of DLImentioning

confidence: 99%

Optimization of Donor Lymphocyte Infusion for AML Relapse After Allo-HCT in the Era of New Drugs and Cell Engineering

Yang

Yuan

et al. 2022

Front. Oncol.

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“…These results suggest that these patients may need a more intensive therapy to achieve negative MRD results. Several novel drugs, such as hypomethylating agents [ 28 ] and Bcl‐2 inhibitors [ 29 ] have been used in combination with DLI in some pilot studies, and an enhanced GvL effect was observed [ 30 ]. However, this warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

Optimized therapeutic strategy for patients with refractory or relapsed acute myeloid leukemia: long‐term clinical outcomes and health‐related quality of life assessment

Yan

Wang

Sun

et al. 2022

Cancer Communications

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Background Patients with refractory or relapsed acute myeloid leukemia (AML) have poor survival, necessitating the exploration of optimized therapeutic strategy. Here, we aimed to investigate clinical outcomes and health‐related quality of life (HR‐QoL) after total therapy, which included allogeneic hematopoietic stem cell transplantation (allo‐HSCT), and prophylactic donor lymphocyte infusion (DLI) in the early phase after transplantation, followed by multiple measurable residual disease (MRD) and graft‐versus‐host disease (GvHD)‐guided DLIs. Methods Consecutive patients who had refractory or relapsed AML and had received non‐T‐cell‐depleted allo‐HSCT at Peking University Institute of Hematology were included in the study. If the patients achieved complete remission at 30 days after transplantation and had no evidence of relapse, severe infection, organ failure, and active GvHD at the time of planned DLI, prophylactic DLI was administered at 30 days after transplantation for human leukocyte antigen (HLA)‐matched related HSCT or at 45‐60 days after transplantation for haploidentical or unrelated HSCT. Subsequently, multiple DLIs were administered based on MRD results and whether they developed GvHD after transplantation. Results A total of 105 patients were eligible. Eighty‐seven patients received prophylactic DLI (group B), while 18 did not receive prophylactic DLI (group A). Among 105 patients, the cumulative incidence of grade 2‐4 acute GvHD and chronic GvHD was 40.6% (95% confidence interval [CI] = 30.6%‐50.6%) and 73.3% (95% CI = 67.4%‐79.2%), respectively. The cumulative incidence of relapse (CIR), transplant‐related mortality (TRM), and leukemia‐free survival (LFS) at 5 years after transplantation were 31.5% (95% CI = 21.9%‐41.1%), 22.1% (95% CI = 11.3%‐32.9%), and 46.4% (95% CI = 36.8%‐56.0%), respectively. In group B, the CIR, TRM, and LFS at 5 years after transplantation were 27.6% (95% CI = 17.6%‐37.6%), 21.6% (95% CI = 11.2%‐32.0%), and 50.8% (95% CI = 40.0%‐61.6%), respectively. At the end of follow‐up, 48 patients survived, and more than 90% of survivors had satisfactory recoveries of HR‐QoL. Conclusions Our study indicated that total therapy is not only associated with decreased CIR, comparable TRM, and better long‐term LFS, but also with satisfactory HR‐QoL for refractory or relapsed AML, compared with those of standard of care therapy reported previously. Therefore, total therapy may be an optimized therapeutic strategy for refractory or relapsed AML.

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“…Reduced-intensity conditioning HSCT resulted in a significantly improved event-free survival in comparison with azacytidine [36 ▪▪ ]. Although haploidentical transplant is increasing steadily, providing more patients with available donors, after the demonstration some years ago of maintenance with cc486, the prevention of relapse is proposed by continuous therapy with DLI and low-dose HMAs [37].…”

Section: Discussionmentioning

confidence: 99%

Advances in myelodysplastic syndrome

Santini

2021

Current Opinion in Oncology

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Purpose of reviewIn this review, the focus is on the most recent improvements in diagnosis, prognostication and therapy of myelodysplastic syndromes (MDS) and on their relevance for clinical management. Recent findingsAnalytical methods to refine cytogenetic and molecular assessment of MDS have been proposed, improving prognostic stratification obtained from integration of clinical and genomic data. Novel agents with very different mode of action, as single drugs or added to HMA backbone, show promising clinical results in LR-MDS and HR-MDS. Luspatercept has obtained approval given the fact that in transfusion-dependent erythropoietic-stimulating agent resistant/relapsed LR-MDS induced nearly 50% of transfusion independence. Another investigational agent showing efficacy and possibly disease modifying activity in the same setting is the telomerase inhibitor imetelstat. Results from phase II study with azacytidine and pevonedistat indicate the concrete possibility to enhance durable responses compared with azacitidine single drug. In the same direction are the preliminary results of other agents with different mode of action: magrolimab, venetoclax, sabatolimab, as well as the targeted therapy with enasidenib and ivosidenib. New posttransplant maintenance strategies may concur to prolong response.

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Prophylactic or Preemptive Low-Dose Azacitidine and Donor Lymphocyte Infusion to Prevent Disease Relapse following Allogeneic Transplantation in Patients with High-Risk Acute Myelogenous Leukemia or Myelodysplastic Syndrome

Cited by 26 publications

References 38 publications

Optimization of Donor Lymphocyte Infusion for AML Relapse After Allo-HCT in the Era of New Drugs and Cell Engineering

Optimization of Donor Lymphocyte Infusion for AML Relapse After Allo-HCT in the Era of New Drugs and Cell Engineering

Optimized therapeutic strategy for patients with refractory or relapsed acute myeloid leukemia: long‐term clinical outcomes and health‐related quality of life assessment

Advances in myelodysplastic syndrome

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