FDA Approval: Blinatumomab for Patients with B-cell Precursor Acute Lymphoblastic Leukemia in Morphologic Remission with Minimal Residual Disease

Jen, Emily Y.; Xu, Qing; Schetter, Aaron J.; Przepiorka, Donna; Shen, Yuan Li; Roscoe, Donna; Sridhara, Rajeshwari; Deisseroth, Albert; Philip, Reena; Farrell, Ann T.; Pazdur, Richard

doi:10.1158/1078-0432.ccr-18-2337

Cited by 110 publications

(88 citation statements)

References 16 publications

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“…In summary, our data further support the emerging role of positive pre‐MRD, except for low level one (MRD <0.01%), in risk stratification of ALL patients and indicate that MRD status is potentially a pivotal determinant of outcome in ALL patients undergoing haplo‐SCT. In addition, considering the superior survival of patients with negative pre‐MRD to those with a positive one, it is anticipated that transformation of positive pre‐MRD to a negative one with existing therapies, such as Inotuzumab, blinatumomab, and chimeric antigen receptor T cells, as well as the introduction of novel agents, will reduce the posttransplantation relapse rates and improve outcomes in this high risk patient population.…”

Section: Discussionmentioning

confidence: 99%

Minimal residual disease status determined by multiparametric flow cytometry pretransplantation predicts the outcome of patients with ALL receiving unmanipulated haploidentical allografts

Zhao

Liu

et al. 2019

American J Hematol

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This study evaluated the effects of pretransplantation minimal residual disease (pre-MRD) on outcomes of patients with acute lymphoblastic leukemia (ALL) who underwent unmanipulated haploidentical stem cell transplantation (haplo-SCT). A retrospective study including 543 patients with ALL was performed. MRD was determined using multiparametric flow cytometry. Both in the entire cohort of patients and in subgroup cases with T-ALL or B-ALL, patients with positive pre-MRD had a higher incidence of relapse (CIR) than those with negative pre-MRD in MSDT settings (P < 0.01 for all). Landmark analysis at 6 months showed that MRD positivity was significantly and independently associated with inferior rates of relapse (HR, 1.908; P = 0.007), leukemia-free survival (LFS) (HR, 1.559; P = 0.038), and OS (HR, 1.545; P = 0.049). The levels of pre-MRD according to a logarithmic scale were also associated with leukemia relapse, LFS, and OS, except that cases with MRD <0.01% experienced comparable CIR and LFS to those with negative pre-MRD. A risk score for CIR was developed using the variables pre-MRD, disease status, and immunophenotype of ALL. The CIR was 14%, 26%, and 59% for subjects with scores of 0, 1, and 2-3, respectively (P < 0.001). Three-year LFS was 75%, 64%, and 42%, respectively (P < 0.001). Multivariate analysis confirmed the association of the risk score with CIR and LFS.The results indicate that positive pre-MRD, except for low level one (MRD < 0.01%), is associated with poor outcomes in patients with ALL who underwent unmanipulated haplo-SCT.

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Section: Discussionmentioning

confidence: 99%

Minimal residual disease status determined by multiparametric flow cytometry pretransplantation predicts the outcome of patients with ALL receiving unmanipulated haploidentical allografts

Zhao

Liu

et al. 2019

American J Hematol

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“…Another molecule from the tetraspanin family is of interest as a criterion for MRD detection, that is, CD9 [38][39][40]. Its expression is evaluated both in 4-and 6-color FC protocols of the COG study group (M. Borowitz).…”

Section: Conclusion and Discussionmentioning

confidence: 99%

B-Cell Precursors: Immunophenotypic Features in the Detection of Minimal Residual Disease in Acute Leukemia

Чернышева¹,

Grivtsova²,

Popa³

et al. 2020

Normal and Malignant B-Cell

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Minimal residual disease (MRD) as a tool to monitor response to therapy is both a criterion for detailed risk stratification and an independent prognostic factor in childhood acute lymphoblastic leukemia (ALL). Immunological assays particularly flow cytometry (FC) are priority methods in MRD monitoring. Multicolor flow cytometry makes it possible to most fully characterize the immunophenotype of tumor B lymphoblasts and reveal leukemia-associated immunophenotypes not only according to the CD58 and CD38 antigens but also as an additional criterion of aberrancy. This allows you to identify and select individual criteria for further monitoring of minimal residual disease for each patient with ALL. The aim of this chapter is to compare immunophenotyping features of normal B-cell precursors and B-lymphoblasts in acute leukemia and to show possibilities of use of a leukemiaassociated immunophenotype in monitoring of the MRD.

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“…The FDA approval of blinatumomab, a CD19 bispecific T‐cell engager (BiTE), represented the first CD19‐directed approved immunotherapy, after it was found to induce 80% minimum residual disease (MRD)‐negative remission rates and extend median survival to 7.7 months in a pretreated adult population, with responses also seen in children supporting an indication in pediatrics, and further showing superiority in achieving molecular remissions in MRD‐positive patients . This expanded options significantly for patients, allowing for subsequent lines of therapy, such as HSCT, after which progression‐free survival (PFS) was 65% in a heavily pretreated population .…”

Section: Background: B‐cell Development and Antibody‐based Targeting mentioning

confidence: 99%

Updates on CAR T‐cell therapy in B‐cell malignancies

Jacoby

Shahani

Shah

2019

Immunological Reviews

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By increasing disease‐free survival and offering the potential for long‐term cure, chimeric antigen receptor (CAR) T‐cell therapy has dramatically expanded therapeutic options among those with high‐risk B‐cell malignancies. As CAR T‐cell utilization evolves however, novel challenges are generated. These include determining how to optimally integrate CAR T cells into standard of care and overcoming mechanisms of resistance to CAR T‐cell therapy, such as evolutionary stress induced on cancer cells leading to immunophenotypic changes that allow leukemia to evade this targeted therapy. Compounding these challenges are the limited ability to determine differences between various CAR T‐cell constructs, understanding the generalizability of trial outcomes from multiple sites utilizing unique CAR manufacturing strategies, and comparing distinct criteria for toxicity grading while defining optimal management. Additionally, as understanding of CAR behavior in humans has developed, strategies have appropriately evolved to proactively mitigate toxicities. These challenges offer complimentary insights and guide next steps to enhance the efficacy of this novel therapeutic modality. With a focus on B‐cell malignancies as the paradigm for effective CAR T‐cell therapy, this review describes advances in the field as well as current challenges and future directions.

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FDA Approval: Blinatumomab for Patients with B-cell Precursor Acute Lymphoblastic Leukemia in Morphologic Remission with Minimal Residual Disease

Cited by 110 publications

References 16 publications

Minimal residual disease status determined by multiparametric flow cytometry pretransplantation predicts the outcome of patients with ALL receiving unmanipulated haploidentical allografts

Minimal residual disease status determined by multiparametric flow cytometry pretransplantation predicts the outcome of patients with ALL receiving unmanipulated haploidentical allografts

B-Cell Precursors: Immunophenotypic Features in the Detection of Minimal Residual Disease in Acute Leukemia

Updates on CAR T‐cell therapy in B‐cell malignancies

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