Preliminary Data from a Phase 1 Study of JSP191, an Anti-CD117 Monoclonal Antibody, in Combination with Low Dose Irradiation and Fludarabine Conditioning Is Well-Tolerated, Facilitates Chimerism and Clearance of Minimal Residual Disease in Older Adults with MDS/AML Undergoing Allogeneic HCT

Muffly, Lori; Lee, Catherine J.; Gandhi, Arpita; Varma, Ankur; Scott, Bart L.; Kwon, Hye-Sook; Yanagiba, Chikako; Arulprakasam, Jeyakavitha; Reddy, Mamatha M.; Heller, Kevin N.; Shizuru, Judith A.; Pang, Wendy W.; Artz, Andrew S.

doi:10.1016/s2666-6367(22)00784-9

Cited by 3 publications

(3 citation statements)

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“…78,79 The adjunctive use of sorafenib, a FLT3 tyrosine kinase inhibitor, in combination with fractionated myeloablative conditioning, has been shown to be tolerable in patients allografted for FLT3-ITD-mutated AML. 80 In the non-myeloablative setting, the addition of the CD117-targeting monoclonal antibody JSP191 appears safe, resulting in high levels of donor stem cell engraftment, 81 while in patients with relapsed or refractory AML the ongoing SIERRA trial is examining the use of an I-labelled anti-CD45 monoclonal antibody in conjunction with a non-myeloablative fludarabine/low-dose TBI conditioning regimen. 82 Overall, these studies demonstrate the feasibility of delivering combination therapy within conditioning regimens but larger prospective trials with longer follow-up will be required to change current practice.…”

Section: Op Ti M Isi Ng T H E Con Dition I Ng R Egi M E N To Pr Ev E ...mentioning

confidence: 99%

Strategies to reduce relapse risk in patients undergoing allogeneic stem cell transplantation for acute myeloid leukaemia

Kinsella,

Maroto,

Loke

et al. 2024

Br J Haematol

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SummaryAllogeneic stem cell transplantation is a centrally important curative strategy in adults with acute myeloid leukaemia; however, relapse occurs in a significant proportion of patients and remains the leading cause of treatment failure. The prognosis for patients who relapse post‐transplant remains poor, and the development of new strategies with the ability to reduce disease recurrence without increasing transplant toxicity remains a priority. In this review, within the context of our understanding of disease biology and the graft‐versus‐leukaemia (GVL) effect, we will discuss established, evolving and novel approaches for increasing remission rates, decreasing measurable residual disease pretransplant, future methods to augment the GVL effect and the opportunities for post‐transplant maintenance. Future progress depends upon the development of innovative trials and networks, which will ensure the rapid assessment of emerging therapies in prospective clinical trials.

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Section: Op Ti M Isi Ng T H E Con Dition I Ng R Egi M E N To Pr Ev E ...mentioning

confidence: 99%

Strategies to reduce relapse risk in patients undergoing allogeneic stem cell transplantation for acute myeloid leukaemia

Kinsella,

Maroto,

Loke

et al. 2024

Br J Haematol

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“…JSP191 depletes both hematopoietic stem cells and leukemic cells and synergizes with total body irradiation and fludarabine facilitating engraftment. 100 The phase I study reporting the outcomes of 17 patients was presented at the Tandem meetings in 2022. The combination was safe without any infusion or serious adverse effects observed.…”

Section: Novel Approaches In Allogeneic Hematopoietic Cell Transplant...mentioning

confidence: 99%

New drugs before, during, and after hematopoietic stem cell transplantation for patients with acute myeloid leukemia

et al. 2023

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The treatment of acute myeloid leukemia (AML) has evolved over the past few years with the advent of next-generation sequencing. Targeted therapies alone or in combination with low-dose or high-intensity chemotherapy have improved the outcome of patients with AML treated in the frontline and relapsed/refractory settings. Despite these advances, allogeneic stem cell transplantation (allo-HCT) remains essential as consolidation therapy following frontline treatment in intermediate-and adverse-risk and relapsed/refractory disease. However, many patients relapse, with limited treatment options, hence the need for post-transplant strategies to mitigate relapse risk. Maintenance therapy following allo-HCT was developed for this specific purpose and can exploit either a direct anti-leukemia effect and/or enhance the bona fide graft-versus-leukemia effect without increasing the risk of graft-versus-host disease. In this paper, we summarize novel therapies for AML before, during, and after allo-HCT and review ongoing studies.

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“…Monoclonal antibodies (MABs) may be coupled with radioisotopes to deliver targeted radioimmunotherapy to leukocyte progenitor cells with targets including anti-CD45 and anti-CD117, among others. JSP191 is an anti-CD117 MAB that is being studied in combination with fludarabine and low-dose TBI for patients with MDS or AML with pre-transplant evidence of MRD (NCT04429191) [ 45 ]. High rates of MRD clearance were observed in the first 17 patients, which appear to persist beyond day 30, presented at the 2,022 Tandem meeting with full results awaited.…”

Section: Novel Conditioning Approachesmentioning

confidence: 99%

Test Then Erase? Current Status and Future Opportunities for Measurable Residual Disease Testing in Acute Myeloid Leukemia

Blackmon,

Hourigan

2023

Acta Haematol

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Background: Measurable residual disease (MRD) test positivity during and after treatment in patients with acute myeloid leukemia (AML) has been associated with higher rates of relapse and worse overall survival. Current approaches for MRD testing are not standardized leading to inconsistent results and poor prognostication of disease. Pertinent studies evaluating AML MRD testing at specific times points, with various therapeutics and testing methods are presented. Summary: AML is a set of diseases with different molecular and cytogenetic characteristics, and is often polyclonal with evolution over time. This genetic diversity poses a great challenge for a single AML MRD testing approach. The current ELN 2021 MRD guidelines recommend MRD testing by quantitative polymerase chain reaction (qPCR) in those with a validated molecular target or multiparameter flow cytometry (MFC) in all other cases. The benefit of MFC is the ability to use this method across disease subsets, at the relative expense of suboptimal sensitivity and specificity. AML MRD detection may be improved with molecular methods. Genetic characterization at AML diagnosis and relapse is now standard of care for appropriate therapeutic assignment, future initiatives will provide the evidence to support testing in remission to direct clinical interventions. Key Messages: The treatment options for patients with AML have expanded for specific molecular subsets such as FLT3 and IDH1/2 mutated AML, with development of novel agents for NPM1 mutated or KMT2A rearranged AML ongoing, but also due to effective venetoclax-combinations. Evidence regarding highly sensitive molecular MRD detection methods for specific molecular subgroups, in the context of these new treatment approaches, will likely shape the future of AML care.

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Preliminary Data from a Phase 1 Study of JSP191, an Anti-CD117 Monoclonal Antibody, in Combination with Low Dose Irradiation and Fludarabine Conditioning Is Well-Tolerated, Facilitates Chimerism and Clearance of Minimal Residual Disease in Older Adults with MDS/AML Undergoing Allogeneic HCT

Cited by 3 publications

References 0 publications

Strategies to reduce relapse risk in patients undergoing allogeneic stem cell transplantation for acute myeloid leukaemia

Strategies to reduce relapse risk in patients undergoing allogeneic stem cell transplantation for acute myeloid leukaemia

New drugs before, during, and after hematopoietic stem cell transplantation for patients with acute myeloid leukemia

Test Then Erase? Current Status and Future Opportunities for Measurable Residual Disease Testing in Acute Myeloid Leukemia

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