High Rates of Transplantation in the Phase III Sierra Trial Utilizing Anti-CD45 (Iodine) 131I-Apamistamab (Iomab-B) Conditioning with Successful Engraftment and Tolerability in Relapsed Refractory (R/R) Acute Myeloid Leukemia (AML) Patients after Lack of Response to Conventional Care and Targeted Therapies

Gyurkocza, Boglarka; Nath, Rajneesh; Seropian, Stuart; Choe, Hannah; Litzow, Mark R.; Koshy, Nebu; Stiff, Patrick J.; Abboud, Camille N.; Tomlinson, Benjamin; Abhyankar, Sunil; Hari, Parameswaran; Chen, George L.; Al-Kadhimi, Zaid; Sabloff, Mitchell; Orozco, Johnnie J.; Foran, James M.; Kebriaei, Partow; Jamieson, Katarzyna; Magalhaes-Silverman, Margarida; Besien, Koen van; Schuster, Michael W.; Law, Arjun; Levy, Moshe; Lazarus, Hillard M.; Giralt, Sergío; Berger, Mark S.; Spross, Jennifer; Desai, Avinash; Reddy, Vijay; Pagel, John M.

doi:10.1016/s2666-6367(22)00201-9

Cited by 5 publications

(7 citation statements)

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“… 89 Other conditioning regimens recently developed for allo-HCT of active or refractory AML include targeted radiation therapy using anti-CD45 monoclonal antibody ( Table 2 and Table 3 ). 90 Novel therapies for use in AML during and after allo-HCT are secribed below. Those for which results have been published are summarized in Table 2 .…”

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

confidence: 99%

“…The SIERRA trial (Study for Iomab-B in Elderly Relapsed or Refractory AML) investigated using Iomab-B, a 131 I-labeled anti-CD45 monoclonal antibody, as conditioning prior to allo-HCT. 90 , 102 Patients were randomized to receive Iomab-B followed by fludarabine and low-dose total body irradiation, or conventional care. The median age of the participants was 65 years.…”

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

confidence: 99%

“…These data show that the Iomab-B-based conditioning regimen is safe and associated with acceptable engraftment kinetics. 90 , 102 …”

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

confidence: 99%

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

confidence: 99%

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

confidence: 99%

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

et al. 2023

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“…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. The phase 3 SIERRA trial (Study of Iomab-B in Elderly Relapsed or Refractory AML) investigating the use of Iomab-B, an 131 I-labeled anti-CD45 MAB in patients who have lack of response to standard-of-care regimens and targeted therapy [46] demonstrated that 74.6% (44/59) of evaluable patients on the Iomab-B arm achieved initial CR/ CRp compared to only 6.3% (4/64) evaluable on the conventional care arm. Durable CR rates at 6 months were 22% versus 0% (95% CI: 12.29, 34.73; p < 0.0001) [47].…”

Section: Current Practices Of Mrd In Amlmentioning

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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“…1,[5][6][7] Furthermore, with an expanded donor pool, advances in transplantation-specific conditioning regimens, and novel peritransplant strategies, allo-HCT is now being offered to a wider group of patients including those of an advanced age, and in some instances, also considered in those not achieving CR. 1,[8][9][10] Given the potentially curative nature of allo-HCT for acute leukemia, it is important to determine the proportion of patients with newly diagnosed or relapsed disease proceeding to transplant and to ascertain barriers to transplantation in the current era. In this prospective observational study, all newly diagnosed or relapsed adult patients with acute leukemia were enrolled at the time of induction or reinduction therapy and followed throughout their treatment journey to determine the rate of allo-HCT in patients for whom transplant was initially recommended.…”

Section: Introductionmentioning

confidence: 99%

Prospective analysis to determine barriers to allogeneic hematopoietic cell transplantation in patients with acute leukemia

Nath,

Lee,

Elko

et al. 2023

American J Hematol

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Allogeneic hematopoietic cell transplantation (allo‐HCT) is a potentially curative treatment for patients with acute leukemia. Despite this, studies have shown that only a minority of patients ultimately proceed to allo‐HCT. The primary objective of this prospective, observational study was to identify the rate of allo‐HCT in patients for whom it was recommended, and reasons why patients deemed appropriate and eligible for HCT did not subsequently undergo transplant. Between April 2016 and April 2021, adult patients with newly diagnosed or relapsed/refractory acute leukemia were enrolled at the time of induction/reinduction therapy. Initial transplantation workup and allo‐HCT recommendations were made during the early phase of induction/reinduction. Of the 307 enrolled patients, allo‐HCT was recommended to 85% (n = 259), of whom 66% (n = 170) underwent transplant. Donor sources comprised 54% human leukocyte antigen (HLA)‐matched unrelated donors, 20% HLA‐matched sibling donors and HLA‐mismatched graft sources with 15% umbilical cord blood units, 8% HLA‐mismatched unrelated donors, and 4% HLA‐haploidentical donors. The most common reason for transplant disqualification in the 89 patients in whom it was initially recommended was persistent/relapsed disease (70%), followed by early patient death (10%). In this prospective study, we report a high allo‐HCT rate, which may be due to early transplant referral and workup. The main allo‐HCT barrier was disease control, followed by early patient death. With the increasing availability of HLA‐mismatched graft sources, the lack of donor availability was not a transplant barrier. Further development of novel transplant strategies for patients not achieving remission and improvements in induction regimens could result in increased allo‐HCT utilization.

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Cited by 5 publications

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

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

Prospective analysis to determine barriers to allogeneic hematopoietic cell transplantation in patients with acute leukemia

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