Don't Get Stuck on the Shoulder: Radiation Oncologists Should Get Into the CAR With T-Cell Therapies

Plastaras, John P.; Chong, Elise A.; Schuster, Stephen J.

doi:10.1016/j.ijrobp.2019.09.005

Cited by 4 publications

(4 citation statements)

References 12 publications

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“…7 Although the long-term durability of RT response for chemotherapy-refractory LBCL is moderate, in the bridging setting, RT can effectively address burdensome disease and may improve outcomes when coupled with cellular therapy. 6,[8][9][10] RT has been shown to enable presentation of tumor-associated antigens for the priming of antigen-specific T cells, facilitate homing of antigenspecific T cells, and augment effector function and proliferation of native and adoptively transferred T cells. 11 Preclinical data in a pancreatic adenocarcinoma model suggest that RT conditioning may promote susceptibility to CAR therapy and decrease antigennegative tumor relapse.…”

Section: Introductionmentioning

confidence: 99%

Bridging therapy prior to axicabtagene ciloleucel for relapsed/refractory large B-cell lymphoma

Pinnix¹,

Gunther²,

Dabaja³

et al. 2020

Blood Advances

178

143

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Abstract The impact of bridging therapy (BT) administered between leukapheresis and chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL) is unclear. We evaluated the influence of BT (systemic therapy [ST], radiation therapy [RT], or combined-modality therapy [CMT]) on outcomes of 148 LBCL patients who underwent leukapheresis for planned axicabtagene ciloleucel (axi-cel) infusion. The 55% (n = 81) of patients who received BT were more likely to have international prognostic index (IPI) score ≥3 (P ≤ .01), bulky disease (P = .01), and elevated lactate dehydrogenase (LDH; P ≤ .01). The 1-year progression-free (PFS) and overall survival (OS) rates were 40% and 65% in non-BT patients vs 21% and 48% in BT patients (P = .01 and .05, respectively). Twenty-four patients (16%) did not receive axi-cel, most commonly because of lymphoma progression (88%), despite 80% (n = 19) receiving BT. Among 124 patients who received axi-cel, 50% (n = 62) received BT with ST (n = 45), RT (n = 11), or CMT (n = 6); 1-year PFS and OS rates were not significantly different between BT and non-BT cohorts (P = .06 and .21, respectively). There was no difference in proportion of patients with IPI ≥3, limited-stage disease, or elevated LDH between ST, RT, and CMT groups. Compared with non-BT patients, 1-year PFS was inferior for ST-bridged patients (P = .01). RT-bridged patients had improved PFS compared with ST-bridged patients (P = .05). Despite the poor prognosis associated with requiring BT, RT can be an effective bridging strategy. Future studies are necessary to identify strategies that may improve access to CAR T-cell therapy and outcomes.

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Section: Introductionmentioning

confidence: 99%

Bridging therapy prior to axicabtagene ciloleucel for relapsed/refractory large B-cell lymphoma

Pinnix¹,

Gunther²,

Dabaja³

et al. 2020

Blood Advances

178

143

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“…To our knowledge, this is the first time that sTLI and TMI have been used as bridging therapies to CAR T cell infusion in a chemorefractory leukemic DLBCL. In general, RT appears particularly attractive as bridging therapy to CAR T cells, especially in patients with highly chemorefractory (10,(16)(17)(18) and high tumor burden (19). In one study, bridging RT was superior to bridging chemo-immunotherapy in terms of PFS (10), allowing all patients to receive CAR T cells (axicabtagene) versus 74 and 67% of patients who underwent other forms of bridging therapy.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Subtotal Lymphoid and Total Marrow Irradiation as Bridge Therapy to CD19-Directed CAR T Cells in a Chemorefractory DLBCL With Leukemic Involvement

et al. 2022

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CAR T cell therapy has transformed the salvage approach for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Maintaining disease control before CAR T cell infusion during product manufacturing (so-called bridging therapy) is an important step to optimizing outcome. Among possible bridging therapies, radiation therapy (RT) represents a valuable option, particularly when the disease is limited. Here, we report for the first time on a patient with chemorefractory-transformed DLBCL showing nodal, extranodal, and massive bone marrow (BM) lymphoma infiltration associated with leukemic involvement, a successful bridge therapy to CD19-directed CAR T cell therapy by subtotal lymphoid/total marrow irradiation plus thiothepa followed by reinfusion of CD34+ autologous hematopoietic stem cells. Such a novel bridging regimen allowed a significant reduction of nodal and BM tumor volume while improving blood cell count before CAR T cell infusion. The PET-CT scan and BM evaluation performed at 1, 3, and 6 months after treatment showed complete remission of the disease. A relapse occurred at almost 1 year in lymph nodes because of CD19 antigen escape while the BM remained free of disease. This extended radiotherapy approach may be an effective bridging therapy for chemorefractory DLBCL patients eligible for CAR T cells who present with a high tumor burden, including massive BM involvement associated with leukemic involvement. This preliminary evidence is worth confirming in additional patients.

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“…Once the CAR recognizes and binds to CD19+ cells [40], a series of signaling events are triggered, starting with the phosphorylation of ITAMs and culminating in the activation, expansion, and persistence of modified lymphocytes. Additionally, these lymphocytes acquire effector functions, secrete proinflammatory cytokines and chemokines, and release cytotoxic granules that exert a direct lytic effect over target cells [41].…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

“…remaining 12%, RFS at 65%, CRS in 22% of patients, neurological adverse effects in 12% of cases, cytopenias in 32% of individuals, and prevalence of 20% in terms of infections. Schuster et al[41] …”

mentioning

confidence: 99%

Car T Cells in Solid Tumors: Overcoming Obstacles

Rojas-Quintero,

Díaz,

Palmar

et al. 2024

IJMS

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Chimeric antigen receptor T cell (CAR T cell) therapy has emerged as a prominent adoptive cell therapy and a therapeutic approach of great interest in the fight against cancer. This approach has shown notorious efficacy in refractory hematological neoplasm, which has bolstered its exploration in the field of solid cancers. However, successfully managing solid tumors presents considerable intrinsic challenges, which include the necessity of guiding the modified cells toward the tumoral region, assuring their penetration and survival in adverse microenvironments, and addressing the complexity of identifying the specific antigens for each type of cancer. This review focuses on outlining the challenges faced by CAR T cell therapy when used in the treatment of solid tumors, as well as presenting optimizations and emergent approaches directed at improving its efficacy in this particular context. From precise localization to the modulation of the tumoral microenvironment and the adaptation of antigen recognition strategies, diverse pathways will be examined to overcome the current limitations and buttress the therapeutic potential of CAR T cells in the fight against solid tumors.

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Don't Get Stuck on the Shoulder: Radiation Oncologists Should Get Into the CAR With T-Cell Therapies

Cited by 4 publications

References 12 publications

Bridging therapy prior to axicabtagene ciloleucel for relapsed/refractory large B-cell lymphoma

Bridging therapy prior to axicabtagene ciloleucel for relapsed/refractory large B-cell lymphoma

Case Report: Subtotal Lymphoid and Total Marrow Irradiation as Bridge Therapy to CD19-Directed CAR T Cells in a Chemorefractory DLBCL With Leukemic Involvement

Car T Cells in Solid Tumors: Overcoming Obstacles

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