Extramedullary relapse and discordant CD19 expression between bone marrow and extramedullary sites in relapsed acute lymphoblastic leukemia after blinatumomab treatment

Demosthenous, Christos; Lalayanni, Chrysavgi; Iskas, Michalis; Douka, Vassiliki; Pastelli, Nikoleta; Anagnostopoulos, Achilles

doi:10.1016/j.currproblcancer.2018.04.006

Cited by 21 publications

(18 citation statements)

References 14 publications

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“…Extramedullary disease relapse, particularly in immune privileged sites and including but not limited to CNS disease, has been reported following blinatumomab treatment. 38,39 In some cases, these relapses occurred in the absence of morphologic disease and even in the setting of bone marrow MRD negativity, 38,39 raising concerns about the potential for an increase in nonmarrow relapse following single-agent blinatumomab treatment. This highlights the need for a combination approach, using therapies with nonoverlapping distributions, to mitigate this potential mechanism of resistance.…”

Section: Mechanisms Of Resistance To Blinatumomabmentioning

confidence: 99%

Taking a “BiTE out of ALL”: blinatumomab approval for MRD-positive ALL

Curran

Stock

2019

Blood

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Blinatumomab, a bispecific T-cell engager (BiTE) associated with improved survival in relapsed or refractory acute lymphoblastic leukemia (ALL), was recently approved for treatment of minimal residual disease (MRD). MRD is an important predictor of survival in ALL, and recent studies suggest that achievement of MRD-negativity with blinatumomab improves outcomes in patients with ALL. However, further research is needed to determine how to optimally incorporate blinatumomab, and other novel therapies, into current therapies for ALL.

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Section: Mechanisms Of Resistance To Blinatumomabmentioning

confidence: 99%

Taking a “BiTE out of ALL”: blinatumomab approval for MRD-positive ALL

Curran

Stock

2019

Blood

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“…EM relapse following blinatumomab treatment has been described in a limited number of reports (Table 3). [14][15][16][17][18] Aldoss et al found EM relapse in 21 (32%) of 65 patients in a retrospective analysis, which included 13 of 32 (41%) patients refractory to treatment and 8 of 20 (40%) patients who responded but eventually relapsed to blinatumomab. Sites of relapse included the kidney, central nervous system (CNS), lymph node, muscle, chest wall, and nasopharynx.…”

Section: Discussionmentioning

confidence: 99%

“…13 Several case reports have described unusual relapse patterns following blinatumomab to uncommon sites including the lungs, lymph nodes, kidney, and spleen. [14][15][16] Only one study has presented a detailed analysis of EM relapse, treatment failure, and resistance patterns after blinatumomab treatment at a single institution. Aldoss et al 15 reported EM relapse in 40% of their patients who subsequently relapsed after blinatumomab.…”

Section: Introductionmentioning

confidence: 99%

Characterization of relapse patterns in patients with acute lymphoblastic leukemia treated with blinatumomab

Lau

Saunders

Goodman

2020

J Oncol Pharm Pract

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Introduction Blinatumomab is a CD19/CD3 bispecific T-cell engager (BiTE) antibody that simultaneously binds CD19 on the surface of B-cells and CD3 on the surface of T-cells, resulting in tumor cell lysis. It is approved for the treatment of patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and in patients with minimal residual disease after intensive induction chemotherapy. Relapse patterns after treatment with blinatumomab have not been well characterized. Methods We reviewed patients treated with blinatumomab with relapsed, refractory or minimal residual disease-positive B-ALL from 1 December 2014 to 31 December 2018 at a single academic medical center. Patient demographics, blast percentage prior to blinatumomab initiation, prior lines of therapy, blinatumomab treatment duration, sites of relapse, progression free survival, and overall survival were collected. Results A total of 20 patients were identified. Four (20%) patients developed extramedullary relapse following blinatumomab. The median time from treatment initiation to extramedullary relapse was 179 days (range 47–241). Sites of extramedullary relapse included the pancreas, adrenal gland, kidneys, liver, parotid gland, and brain. Conclusion Extramedullary relapse occurs frequently following treatment of B-ALL with blinatumomab. Further studies aimed at preventing extramedullary relapse following blinatumomab treatment are warranted.

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“…In the era of novel biologic, immune and cellular therapies, the natural course of EMR after allo-HCT is expected to change dramatically. A few case reports have suggested hints of these expectations with blinatumomab reported to induce discordant CD19 expression between bone marrow and extramedullary sites [23]. Another report showed a GVL effect of blinatumomab in relapsed ALL patients after allo-HCT [24].…”

Section: Discussionmentioning

confidence: 99%

Isolated Extramedullary Relapse as a Poor Predictor of Survival after Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia

Sakellari

Gavriilaki

Batsis

et al. 2019

Biology of Blood and Marrow Transplantation

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Limited and conflicting data exist on outcomes of patients with extramedullary relapses (EMRs) after allogeneic hematopoietic cell transplantation (allo-HCT) for acute leukemias. We retrospectively reviewed charts of consecutive allo-HCT recipients who underwent transplantation in our center with the indication of acute leukemia (July 1990 to July 2018). Incidences of isolated EMR (iEMR) and bone marrow relapse (BMR) were calculated using cumulative incidence (CI) analysis, with each and treatment-related mortality considered a competing risk. We studied 554 allo-HCT recipients for 1.8 years (range, .04 to 27.75). Ten-year CI of 10.5% for iEMR was associated only with advanced disease phase at transplantation, whereas 10-year CI of 34.8% for BMR was independently associated with pretransplant disease phase, lines of treatment, and fungal infections. Most iEMR and BMR patients (75% and 81%, respectively) received systemic treatment combined with local radiation for iEMR (26%) and donor lymphocyte infusions (16% and 28%, respectively) when feasible. Extensive chronic graft-versus-host disease (GVHD) was recorded in 47% of iEMR and 48% of BMR patients. Outcomes were poor both in iEMR (10year overall survival [OS], 18.3%) and BMR (10-year OS, 19.1%). Independent predictors of OS were disease phase, type of donor, acute and chronic GVHD, fungal infections, iEMR, and BMR. In a large population with long-term follow-up, incidence of iEMR was relatively high, developed at the late post-transplant period, and was associated only with disease phase at transplantation. Furthermore, iEMR and BMR conferred similarly poor outcomes despite systemic treatment or extensive chronic GVHD.

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Extramedullary relapse and discordant CD19 expression between bone marrow and extramedullary sites in relapsed acute lymphoblastic leukemia after blinatumomab treatment

Cited by 21 publications

References 14 publications

Taking a “BiTE out of ALL”: blinatumomab approval for MRD-positive ALL

Taking a “BiTE out of ALL”: blinatumomab approval for MRD-positive ALL

Characterization of relapse patterns in patients with acute lymphoblastic leukemia treated with blinatumomab

Isolated Extramedullary Relapse as a Poor Predictor of Survival after Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia

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