Phase I Trial of Post Allogeneic Stem Cell Transplant Maintenance Lenalidomide in Patients with High Risk Acute Myeloid Leukemia or Myelodysplastic Syndrome

Background: Patients (pts) with High-risk Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) often proceed to allogeneic hematopoietic stem cell transplant (alloHSCT) due to poorer outcomes. This is the only chance of cure; however, relapse rates after alloHSCT remain high and range between 25-50%. Maintenance approaches post-HSCT, such as hypomethylating agents or tyrosine kinase inhibitors, have been used to decrease the relapse rate with mixed results. Lenalidomide is known to augment T/NK cell activity/proliferation which lead us to hypothesize that it will enhance the Graft-versus-Leukemia (GvL) effect without increasing the incidence of acute Graft-versus-Host (GvH).
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research

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Immunotherapy has revolutionized therapy in both solid and liquid malignancies. The ability to cure acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) with an allogeneic hematopoietic stem cell transplant (HSCT) is proof of concept for the application of immunotherapy in AML and MDS. However, outside of HSCT, only the anti-CD33 antibody drug conjugate gemtuzumab ozogamicin is currently approved as an antibody-targeted therapy for AML. Several avenues of immunotherapeutic drugs are currently in different stages of clinical development.
Source: Blood Reviews - Category: Hematology Authors: Tags: Review Source Type: research
This study may open up new potential therapeutic avenues for the treatment of patients with chronic infection, inflammatory diseases, and cancer.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - Category: Hematology Authors: Tags: 506. Hematopoiesis and Stem Cells: Microenvironment, Cell Adhesion, and Stromal Stem Cells Source Type: research
BACKGROUND: Recipients of allogeneic HSCT experience significant short- and long-term healthcare burdens with differing general patterns of late effects between graft sources. For example, recipients of peripheral blood stem cell (PBSC) grafts benefit from more rapid engraftment after transplant as compared to bone marrow (BM) or umbilical cord blood (UCB), but experience a greater risk of chronic graft-versus-host disease (cGVHD) at later time points after HSCT. Little data exist regarding healthcare burden beyond first year of allogeneic HSCT, limiting our understanding of the long-term impact for each graft source.METHO...
Source: Blood - Category: Hematology Authors: Tags: 904. Outcomes Research-Malignant Conditions: Outcomes in Myeloid Malignancies and Allogeneic Stem Cell Transplant Source Type: research
Conclusion: OS was nearly threefold higher in the pooled cohort than in patients not receiving ATIR101 after haplo-HSCT in the historic control group. These outcomes were achieved without the need for concomitant high-dose immunosuppressive therapy. Disease relapse was limited and NRM in the pooled cohort was half that of the historic control group. Administration of a single dose of ATIR101 after a T-cell-depleted haplo-HSCT was well tolerated. The rate of GVHD is lower in the pooled cohort than the historic control group, suggesting that ATIR101 does not increase GVHD beyond the levels reported with a T-cell-depleted CD3...
Source: Blood - Category: Hematology Authors: Tags: 711. Cell Collection and Processing I Source Type: research
ConclusionOur first-in-human clinical trial demonstrates promising efficacy of cCAR therapy in treating patients with relapsed/ refractory AML. cCAR is able to eradicate leukemia blasts and leukemia stem cells, exerting a profound tumor killing effect that is superior to single target CAR T cell therapies. cCAR is also shown to induce total myeloid ablation in bone marrow, suggesting that it may act as a safer alternative to avoid the severe toxicities caused by standard bone marrow ablation regimens without sacrificing the anti-tumor efficacy. This strategy will likely benefit patients who are unable to tolerate total bod...
Source: Blood - Category: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Immunotherapy Source Type: research
Conclusions:We have demonstrated the feasibility and safety of multiple injections of CYAD-01 without preconditioning chemotherapy. We evidenced promising anti-leukemic activity with 42% ORR in r/r AML with 5/7 pts having clinical benefit. Rates of G3/4 CRS were low and manageable. Updated safety, activity and correlative science data of the complete dose-escalation segment will be presented.DisclosuresSallman: Celgene: Research Funding, Speakers Bureau. Kerre: Celyad: Consultancy; BMS: Consultancy; Celgene: Consultancy, Research Funding. Davila: Celyad: Consultancy, Membership on an entity's Board of Directors or advisory...
Source: Blood - Category: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Immunotherapy Source Type: research
Dyskeratosis congenita (DC) belongs to the group of inherited bone marrow failure syndromes (IBMFS) and is characterized by premature telomere shortening caused by mutations in components of the telomerase or the shelterin complexes. The main cause of death in affected patients is hematopoietic failure, but there is also a 10-15% risk of malignant transformation into secondary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Critically short telomeres activate a DNA damage response with p53-mediated cell cycle inhibition, senescence and/or apoptosis, the latter mediated primarily by PUMA, a BCL-2 family mem...
Source: Blood - Category: Hematology Authors: Tags: 508. Bone Marrow Failure: Inherited Bone Marrow Failure: Germline Genetic Disorders Source Type: research
We report on updated feasibility and efficacy data.Methods: Pts aged 18-65 yrs with newly diagnosed AML (≥20% blasts by WHO criteria) and high risk MDS (≥10% blasts) were eligible if they had adequate performance status (ECOG ≤2) and organ function. Treatment included 1-2 induction cycles of (A) 1.5 g/m2 over 24 hours (days 1-4) and (I) 12 mg/m2 (days 1-3). Nivo 3 mg/kg was started on day 24±2 and continued every 2 weeks for up to a yr. For pts achieving complete response (CR) or CR with incomplete count recovery (CRi), up to 5 consolidation cycles of attenuated dose I+A was given. Eligible pts received all...
Source: Blood - Category: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Immunotherapy Source Type: research
ConclusionFF-10501-01, was well tolerated and demonstrated evidence of efficacy in a heavily pre-treated population of patients with AML and MDS. FF-10501-01 had predictable pharmacokinetics and pharmacodynamic testing verified its mechanism of action as an IMPDH inhibitor. FF-10501-01 in combination with other agents, is currently undergoing additional clinical testing.DisclosuresKurman: Fujifilm Pharmaceuticals USA, Inc.: Consultancy. DiNardo: Abbvie: Honoraria; Bayer: Honoraria; Medimmune: Honoraria; Agios: Consultancy; Karyopharm: Honoraria; Celgene: Honoraria. Pemmaraju: Affymetrix: Research Funding; SagerStrong Found...
Source: Blood - Category: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster I Source Type: research
Our group developed a 161533 trispecific killer engager (TriKE) molecule to target acute myeloid leukemia (AML) cells using Natural Killer (NK) cells. This molecule contains an anti-CD16 camelid nanobody to activate NK cells, an anti-CD33 single chain variable fragment (scFv) to engage cancer targets, and an IL-15 molecule that drives NK cell priming, expansion and survival. Using an earlier version of this molecule, we have shown that the CD33 TriKE is effective at activating NK cells against AML targets in vitro and in vivo. This preclinical data has lead to the establishment of a clinical trial in refractory AML patient...
Source: Blood - Category: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster I Source Type: research
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