Use of cardiac radiation therapy as bridging therapy to CAR‐T for relapsed pediatric B‐cell acute lymphoblastic leukemia

Márquez, César; Montiel-Esparza, Raúl; Hui, Caressa; Schultz, Liora; Davis, Kara L.; Hoppe, Richard T.; Donaldson, Sarah S.; Ramakrishna, Sneha; Hiniker, Susan M.

doi:10.1002/pbc.28870

Cited by 8 publications

(6 citation statements)

References 24 publications

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“…This combination warrants prospective study to gain a better understanding of the optimal timepoint for incorporation of immune checkpoint inhibition in relation to CAR Tcell infusion and an appropriate duration of therapy with the checkpoint inhibitor. Other bridging strategies, such as radiation therapy (utilized by one patient in our series to eradicate disease pre-CAR), may have a unique role in debulking EMD pre-and/or post-CAR T-cells, but reports are limited 47,52 , and further study is needed. 53 In addition to the limitations of heterogeneity across patients and CAR T-cell constructs, restricting the generalizability of our results, our heavily pretreated cohort may be skewed for a higher incidence of non-CNS EMD.…”

Section: Discussionmentioning

confidence: 99%

Characterization of extramedullary disease in B-ALL and response to CAR T-cell therapy

et al. 2022

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Chimeric antigen receptor (CAR) T-cells effectively eradicate medullary B-cell acute lymphoblastic leukemia (B-ALL) and can traffic to and clear central nervous system (CNS) involvement. CAR T-cell activity in non¬contral nervous system (CNS) extramedullary disease (EMD) has not been well-characterized. We systematically evaluated CAR T-cell kinetics, associated toxicities, and efficacy in B-ALL non-CNS EMD. We conducted a retrospective review of B-ALL patients with non-CNS EMD who were screened for/enrolled on one of three CAR trials at our institution (CD19, CD22, CD19/22). Non-CNS EMD was identified by histology or radiographic imaging at extramedullary sites excluding the cerebrospinal fluid and CNS parenchyma. Of approximately 180 patients with relapsed/refractory B-ALL screened across multiple early phase trials over an 8-year period, 38 (21.1%) presented with isolated non-CNS EMD (n=5) or combined medullary/non-CNS EMD (n=33) on FDG PET-CT imaging. A subset receiving CAR T-cells (18 infusions) obtained FDG PET-CT scans pre- and post-infusion to monitor response. At best response, 72.2% (13 of 18) of patients demonstrated a medullary MRD-negative complete remission and complete (CR, n=7) or partial (PR, n=6) non-CNS EMD response. Non-CNS EMD responses to CAR T-cells were delayed (n=3) and residual non-CNS EMD was substantial; rarely, discrepant responses (marrow without EMD response) were observed (n=2). Unique CAR-associated toxicities at non-CNS EMD sites were seen in select patients. CAR T-cells are active in B-ALL non-CNS EMD. Still, non-CNS EMD response to CAR T-cells may be delayed and sub-optimal, particularly with multifocal disease. Serial FDG PET-CT scans are necessary for identifying and monitoring non-CNS EMD.

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Section: Discussionmentioning

confidence: 99%

Characterization of extramedullary disease in B-ALL and response to CAR T-cell therapy

et al. 2022

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“…There are limited data on the use of bridging radiotherapy prior to CAR T infusion for leukemia, although one prior case report demonstrated its utility in controlling bulky extramedullary cardiac and gastric disease [4] while another provided local control to ocular disease [5]. However, there is a growing body of retrospective studies on the use of bridging therapy for R/R large B-cell lymphoma, with favorable toxicity profiles and oncologic outcomes [14][15][16].…”

Section: Discussionmentioning

confidence: 99%

“…Bridging therapy can include systemic therapies such as steroids, chemotherapy, targeted agents (blinatumomab, inotuzumab), or radiation therapy. There is limited evidence for bridging radiation being used in leukemia, with available literature limited to cases of cardiac and orbital involvement in pediatric B-cell acute lymphoblastic leukemia (B-ALL) [ 4 , 5 ]. Here, we present a patient with multiply relapsed B-ALL with extramedullary recurrence in the testicle that was subsequently treated with orchiectomy and prophylactic bridging radiotherapy to the contralateral testicle and scrotum, which helps enable an effective administration of CAR T therapy with excellent response.…”

Section: Introductionmentioning

confidence: 99%

Adjuvant Scrotal Radiation Therapy As Bridging Therapy to Chimeric Antigen Receptor T-Cell Following Extramedullary Relapse in B-Cell Acute Lymphoblastic Leukemia

Ladbury¹,

Salhotra²,

Dandapani³

2021

Cureus

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Chimeric antigen T-cell (CAR T) therapy is a promising emerging treatment option for patients with relapsed/refractory acute lymphoma. The role of bridging radiotherapy prior to CAR T infusion is an area of increasing interest with a sizable body of literature regarding its use in non-Hodgkin lymphoma, but reports of its use in leukemia are limited. Furthermore, available literature on bridging radiotherapy is limited to the treatment of bulky, often symptomatic disease, as opposed to its role in treating high-risk regions and sanctuary sites. Here, we present an adult male with multiply relapsed B-cell acute lymphoblastic leukemia (B-ALL) who presented with bone marrow relapse and extramedullary relapse in the right testicle. He was successfully treated with right orchiectomy followed by adjuvant bridging radiotherapy to the left testicle and scrotum, followed by CAR T infusion. Under this treatment paradigm, he tolerated the CAR T infusion with minimal toxicity and was without evidence of disease 100 days post-infusion, with normal testosterone levels. This is the first reported case of bridging radiation being used in the adjuvant setting in a patient with hematologic malignancy. This case adds to the growing body of literature that bridging radiation is well-tolerated and can potentially decrease the risk of relapse in high-risk areas following CAR T infusion.

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“…In one study, the median survival times following relapse were 11 months for EMR but only 2 months for BMR [ 29 ]. This is due in part to advances in the early diagnosis and combination treatment of r/r ALL, including in those who experience relapse following allogeneic HSCT [ 28 , 45 , 56 , 88 , 89 , 90 ]. Factors associated with increased risk of EMR include chronic GVHD and a longer duration from stem cell transplantation relapse than that associated with BMR [ 29 ].…”

Section: Prognosis Following Emr Of Allmentioning

confidence: 99%

Cardiac Relapse of Acute Lymphoblastic Leukemia Following Hematopoietic Stem Cell Transplantation: A Case Report and Review of Literature

Sheikh

Ragoonanan

Franklin

et al. 2021

Cancers

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Isolated extramedullary relapse of acute lymphoblastic leukemia (ALL) occurs in soft tissues and various organs outside the testis and central nervous system. Treatments such as hematopoietic stem cell transplantation and more novel modalities such as immunotherapy have eradicated ALL at extramedullary sites. In some instances, survival times for relapsed ALL at these sites are longer than those for relapsed disease involving only the bone marrow. Isolated relapse of ALL in the myocardium is rare, especially in children, making diagnosis and treatment of it difficult. More recent treatment options such as chimeric antigen receptor T-cell therapy carry a high risk of cytokine release syndrome and associated risk of worsening cardiac function. Herein we present the case of an 11-year-old boy who presented with relapsed symptomatic B-cell ALL in the myocardium following allogeneic hematopoietic stem cell transplantation. This is an unusual presentation of relapsed ALL and this case demonstrates the associated challenges in its diagnosis and treatment. The case report is followed by a literature review of the advances in treatment of pediatric leukemia and their application to extramedullary relapse of this disease in particular.

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Use of cardiac radiation therapy as bridging therapy to CAR‐T for relapsed pediatric B‐cell acute lymphoblastic leukemia

Cited by 8 publications

References 24 publications

Characterization of extramedullary disease in B-ALL and response to CAR T-cell therapy

Characterization of extramedullary disease in B-ALL and response to CAR T-cell therapy

Adjuvant Scrotal Radiation Therapy As Bridging Therapy to Chimeric Antigen Receptor T-Cell Following Extramedullary Relapse in B-Cell Acute Lymphoblastic Leukemia

Cardiac Relapse of Acute Lymphoblastic Leukemia Following Hematopoietic Stem Cell Transplantation: A Case Report and Review of Literature

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