PD1 inhibitor in combination with 5-azacytidine and low-dose DLI for the successful treatment of AML patients who relapsed after transplantation

Qian, Chongsheng; Ma, Xiao; Wang, Jin; Wang, Tingjing; Bai, Lian; Zhou, Haixia; Xu, Mingzhu; Sun, Aining; Wu, Depei; Liu, Song‐Bai; Xue, Sheng‐Li

doi:10.1038/s41409-020-01130-8

Cited by 6 publications

(4 citation statements)

References 9 publications

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“…Azacytidine/decitabine and DLI combination showed meaningful results in relapsed patients, but the e ciacy of prophylactic or preemptive treatment remains to be explored 35,36 . Phase I/II single-arm trials and retrospective studies have shown the feasibility and synergistic GVL effect of DLI combined with FLT3 inhibitors, antibodydrug, immune checkpoint inhibitors and venetoclax [37][38][39][40] . Research and clinical trials are urgently needed to explore the best combination and strategy of DLI both in the treatment and prevention of post-transplantation relapse.…”

Section: Discussionmentioning

confidence: 99%

Prophylactic versus Preemptive modified donor lymphocyte infusion for high-risk acute leukemia after allogeneic hematopoietic stem cell transplantation: a multicenter retrospective study

Yang,

Lai,

Yang

et al. 2023

Bone Marrow Transplant

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Donor lymphocyte infusion (DLI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been widely used in preventing post-transplant relapse. We performed an intent-to-treat analysis to compare the clinical outcomes and superiority of prophylactic modi ed DLI (pro-DLI) and preemptive modi ed DLI (pre-DLI) in patients with high-risk relapse features acute leukemia. Pro-DLI was performed in 95 patients, whereas the pre-DLI cohort included 219 patients. Thirty-eight patients in the pre-DLI cohort became MRD positive and received pre-DLI. Pro-DLI cohort had lower 3-year cumulative incidence of relapse (CIR, 25.3% versus 38.0%, P = 0.01) and nonsigni cant trend toward survival bene t (overall survival (OS), 65.2% versus 58.4%, P = 0.24; progression-free-survival (PFS), 63.4% versus 53.7%, P = 0.05). Multivariable analysis demonstrated a strong protective effect of pro-DLI on OS (hazard ratio (HR) = 0.62, P = 0.03), PFS (HR = 0.54, P = 0.003) and CIR (HR = 0.45, P = 0.001). Subgroup analysis of patients who received allo-HSCT at rst complete remission (CR1) indicated that pro-DLI achieved lower 3-year CIR, higher non-relapse mortality (NRM), and no bene t on survival. In patients who received HSCT beyond CR1, pro-DLI signi cantly decreased CIR without increasing NRM and improved survival. Pro-DLI can be recommended for patients with high-risk features who received allo-HSCT beyond CR1 while pre-DLI could be chosen by those who transplanted in CR1.

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Section: Discussionmentioning

confidence: 99%

Prophylactic versus Preemptive modified donor lymphocyte infusion for high-risk acute leukemia after allogeneic hematopoietic stem cell transplantation: a multicenter retrospective study

Yang,

Lai,

Yang

et al. 2023

Bone Marrow Transplant

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“…Some anecdotal cases have shown how the possible association between AZA, PD1 inhibitors, and DLI can represent an effective and safe strategy; PD1 inhibitors combined with HMAs and DLI may enhance the GVL activity of the hosts (donor chimerism) and infused donors’ lymphocytes ( 82 ). Second-generation ICI, targeting TIM or LAG3, or SIRP1a/CD47 directed therapies may give new life to this strategy.…”

Section: Hma-based Combinationsmentioning

confidence: 99%

Hypomethylating Agent-Based Combination Therapies to Treat Post-Hematopoietic Stem Cell Transplant Relapse of Acute Myeloid Leukemia

2022

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Allogeneic stem cell transplantation still represents the best curative option for most patients with acute myeloid leukemia, but relapse is still dramatically high. Due to their immunologic activity and safety profile, hypomethylating agents (HMAs) represent an interesting backbone for combination therapies. This review reports mechanism of action, safety, and efficacy data on combination strategies based on HMAs in the setting of post-allogeneic stem cell transplant relapse. Several studies highlighted how HMAs and donor lymphocyte infusion (DLI) combination may be advantageous. The combination strategy of HMA with venetoclax, possibly in association with DLI, is showing excellent results in terms of response rate, including molecular responses. Lenalidomide, despite its well-known high rates of severe graft-versus-host disease in post-transplant settings, is showing an acceptable safety profile in association with HMAs with a competitive response rate. Regarding FLT3 internal tandem duplication (ITD) mutant AML, tyrosine kinase inhibitors and particularly sorafenib have promising results as monotherapy and in combination with HMAs. Conversely, combination strategies with gemtuzumab ozogamicin or immune checkpoint inhibitors did not show competitive response rates and seem to be currently less attractive strategies. Associations with histone deacetylase inhibitors and isocitrate dehydrogenase 1 and 2 (IDH1/2) inhibitors represent new possible strategies that need to be better investigated.

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“…PD-L1 expression appears irrelevant to the response, implying that the efficacy of DAC plus DIL does not restrict to patients with low leukemic burden [217]. Qian et al [218] reported that 2 patients with relapsed AML post allogeneic SCT achieved durable CRs after combined treatment with anti-PD-1, AZA and low-dose DLI, and no severe immune-related AEs or graft versus host disease (GVHD) developed. The anti-PD-1/HMA/DLI combination possibly enhances the graft-vs-leukemia effect of the host's and infused donor's lymphocytes [218].…”

Section: Advances Of Epi-cell Therapy For Solid and Hematological Can...mentioning

confidence: 99%

“…Qian et al [218] reported that 2 patients with relapsed AML post allogeneic SCT achieved durable CRs after combined treatment with anti-PD-1, AZA and low-dose DLI, and no severe immune-related AEs or graft versus host disease (GVHD) developed. The anti-PD-1/HMA/DLI combination possibly enhances the graft-vs-leukemia effect of the host's and infused donor's lymphocytes [218]. By serial analysis of samples following transgenic T-cell receptor (TCR) T cell infusion, Nowicki et al [219] suggested that rapid loss of surface TCR expression is caused by epigenetic silencing through DNA methylation.…”

Section: Advances Of Epi-cell Therapy For Solid and Hematological Can...mentioning

confidence: 99%

Epi‐immunotherapy for cancers: rationales of epi‐drugs in combination with immunotherapy and advances in clinical trials

Liu

et al. 2022

Cancer Communications

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Over the last two decades, several epi‐drugs, immune checkpoint inhibitors (ICIs) and adoptive cell therapies have received clinical approval for use in certain types of cancer. However, monotherapy with epi‐drugs or ICIs has shown limited efficacy in most cancer patients. Epigenetic agents have been shown to regulate the crosstalk between the tumor and host immunity to alleviate immune evasion, suggesting that epi‐drugs can potentially synergize with immunotherapy. In this review, we discuss recent insights into the rationales of incorporating epigenetic therapy into immunotherapy, called epi‐immunotherapy, and focus on an update of current clinical trials in both hematological and solid malignancies. Furthermore, we outline the future challenges and strategies in the field of cancer epi‐immunotherapy.

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PD1 inhibitor in combination with 5-azacytidine and low-dose DLI for the successful treatment of AML patients who relapsed after transplantation

Cited by 6 publications

References 9 publications

Prophylactic versus Preemptive modified donor lymphocyte infusion for high-risk acute leukemia after allogeneic hematopoietic stem cell transplantation: a multicenter retrospective study

Prophylactic versus Preemptive modified donor lymphocyte infusion for high-risk acute leukemia after allogeneic hematopoietic stem cell transplantation: a multicenter retrospective study

Hypomethylating Agent-Based Combination Therapies to Treat Post-Hematopoietic Stem Cell Transplant Relapse of Acute Myeloid Leukemia

Epi‐immunotherapy for cancers: rationales of epi‐drugs in combination with immunotherapy and advances in clinical trials

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