Tisagenlecleucel in relapsed/refractory diffuse large B-cell lymphoma patients without measurable disease at infusion

Bishop, Michael; Maziarz, Richard T.; Waller, Edmund K.; Jäger, Ulrich; Westin, Jason R.; McGuirk, Joseph P.; Fleury, Isabelle; Holte, Harald; Borchmann, Peter; Corral, Christopher del; Tiwari, Ranjan; Anak, Özlem; Awasthi, Rakesh; Pacaud, Lida; Romanov, Vadim; Schuster, Stephen J.

doi:10.1182/bloodadvances.2019000151

Cited by 71 publications

(49 citation statements)

References 11 publications

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“…All patients sustained CR at 3 months, with 5 of 7 patients remaining progression free .1 year. 23 Additional investigation is required to determine if axi-cel therapy remains effective among patients without PET-CT-detectable disease after BT.…”

Section: Discussionmentioning

confidence: 99%

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

Pinnix¹,

Gunther²,

Dabaja³

et al. 2020

Blood Advances

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163

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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: Discussionmentioning

confidence: 99%

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

Pinnix¹,

Gunther²,

Dabaja³

et al. 2020

Blood Advances

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163

143

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“…In the JULIET study, seven patients experienced CR with bridging therapy, and no measurable disease was observed at the time of tisa-cel infusion (67,68). All seven patients remained in CR at 3 months and had toxicity grades and rates similar to those in the general study.…”

Section: Special Scenarios: Cns Disease Unmeasurable Disease and Sumentioning

confidence: 93%

CAR T-Cell Therapy for B-Cell non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia: Clinical Trials and Real-World Experiences

Vitale

Strati

2020

Front. Oncol.

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Chimeric antigen receptor-modified (CAR) T cells targeting CD19 have revolutionized the treatment of relapsed or refractory aggressive B-cell lymphomas, and their use has increased the cure rate for these cancers from 10 to 40%. Two second-generation anti-CD19 CAR T-cell products, axicabtagene ciloleucel and tisagenlecleucel, have been approved for use in patients, and the approval of a third product, lisocabtagene maraleucel, is expected in 2020. The commercial availability of the first two products has facilitated the development of real-world experience in treating relapsed or refractory aggressive B-cell lymphomas, shed light on anti-CD19 CAR T-cell products' feasibility in trial-ineligible patients, and raised the need for strategies to mitigate the adverse effects associated with anti-CD19 CAR T-cell therapy, such as cytokine release syndrome, neurotoxicity, and cytopenia. In addition, promising clinical data supporting the use of anti-CD19 CAR T-cell therapy in patients with indolent B-cell lymphomas or chronic lymphocytic leukemia have recently become available, breaking the paradigm that these conditions are not curable. Multiple clinical CAR T-cell therapy-based trials are ongoing. These include studies comparing CAR T-cell therapy to autologous stem cell transplantation or investigating their use at earlier stages of disease, novel combinations, and novel constructs. Here we provide a thorough review on the use of the anti-CD19 CAR T-cell products axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel in patients with indolent or aggressive B-cell lymphoma or with chronic lymphocytic leukemia, and present novel CAR T cell-based approaches currently under investigation in these disease settings.

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“…Additional research is needed to better evaluate how expansion is impacted when patients achieve a complete response prior to CAR T-cell therapy. 5 Finally, there is the question of whether bridging therapy can decrease toxicity, specifically grade 3 or higher cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. These toxicities are difficult and expensive to manage as well as potentially fatal.…”

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confidence: 99%

Navigating the narrow bridge to CAR T-cell therapy

Yang

Plastaras

2020

Blood Advances

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When the pivotal phase 2 ZUMA-1 trial was first published in the New England Journal of Medicine in 2017, chimeric antigen receptor (CAR) T-cell therapy was widely regarded as a major breakthrough for patients with refractory diffuse large B-cell lymphoma. These patients, who historically would have had dismal outcomes, had an objective response rate of 82% and an 18-month overall survival of 52%. 1 The results of ZUMA-1 were subsequently bolstered by the JULIET study, in which patients had an equally impressive 12-month relapse-free survival of 65%. 2 Of course, the patients on the ZUMA-1 and JULIET trials were carefully selected, as is the case in most clinical trials, and likely consisted of a less-sick cohort. In particular, the ZUMA-1 trial notably did not allow for any bridging therapy. In reality, patients who are candidates for CAR T-cell therapy often have progressive symptomatic disease that requires some form of treatment to support them during the period between leukapheresis and CAR T-cell infusion.

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Tisagenlecleucel in relapsed/refractory diffuse large B-cell lymphoma patients without measurable disease at infusion

Cited by 71 publications

References 11 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

CAR T-Cell Therapy for B-Cell non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia: Clinical Trials and Real-World Experiences

Navigating the narrow bridge to CAR T-cell therapy

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