3-Year Follow-up Analysis of ZUMA-5: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory (R/R) Indolent Non-Hodgkin Lymphoma (iNHL)

Neelapu, Sattva S.; Chávez, Julio C.; Sehgal, Alison R.; Epperla, Narendranath; Ulrickson, Matthew L.; Bachy, E.; Munshi, Pashna N.; Casulo, Carla; Maloney, David G.; Vos, Sven de; Reshef, Ran; Leslie, Lori A.; Oluwole, Olalekan O.; Yakoub‐Agha, Ibrahim; Khanal, Rashmi; Rosenblatt, Joseph D.; Yan, Jiali; Song, Qinghua; Peng, Weixin; Lui, Christine; Wulff, Jacob; Shen, Rhine R.; Poddar, Soumya; Miao, Harry; Beygi, Sara; Jacobson, Caron A.

doi:10.1182/blood-2022-156120

Cited by 17 publications

(16 citation statements)

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“…Updated findings from the phase 2 ZUMA-5 trial of axicabtagene ciloleucel in patients with r/r indolent non-Hodgkin lymphoma (median follow-up of 40.5 months) demonstrated efficacy comparable with that observed in ELARA, 26 despite fewer patients who were heavily pretreated enrolled in ZUMA-5 than in ELARA (3 vs 4 median lines of prior therapy). 6 , 27 These findings are consistent with the homogeneous treatment effect seen in ELARA regardless of the number of prior lines of therapy, and demonstrates that patient outcomes were still superior to the current non–CAR T-cell therapy SOC.…”

Section: Discussionmentioning

confidence: 92%

“… 11 , 28 , 29 , 30 , 31 , 32 , 33 , 34 Although difficulties with cross-trial comparisons and variation in follow-up duration between the studies limit definitive conclusions, the safety profile of tisagenlecleucel continues to compare favorably with that of axicabtagene ciloleucel. 26 Notably, both ZUMA-5 and the TRANSCEND-FL phase 2 trial allowed the use of bridging therapy at the discretion of the physician. In total, 4% of patients received bridging in ZUMA-5, and 38% to 41% received bridging in TRANSCEND-FL (compared with 45% in ELARA).…”

Section: Discussionmentioning

confidence: 99%

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Durable response after tisagenlecleucel in adults with relapsed/refractory follicular lymphoma: ELARA trial update

Dreyling,

Fowler,

Dickinson

et al. 2024

Blood

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Tisagenlecleucel is approved for adults with relapsed/refractory (r/r) follicular lymphoma (FL) in the ≥3rd-line setting. The primary analysis (median follow-up: 17 months) of the Phase II ELARA trial (ClinicalTrials.gov identifier: NCT03568461) reported high response rates and excellent safety profile in extensively pretreated patients with r/r FL. Here we report longer-term efficacy, safety, pharmacokinetic, and exploratory biomarker analyses after a median follow-up of 29 months. As of March 29, 2022, 97 patients with r/r FL (grades 1-3A) after ≥2 lines of therapy or who relapsed after autologous stem cell transplant received tisagenlecleucel infusion (0.6-6×108 CAR+ viable T cells). Bridging chemotherapy was allowed. Baseline clinical factors, tumor microenvironment (TME), blood soluble factors, and circulating blood cells were correlated with clinical response. Cellular kinetics were assessed by quantitative polymerase chain reaction. Median progression-free survival (PFS), duration of response (DOR), and overall survival (OS) were not reached after 29 months median follow-up (IQR, 22.2-37.7). Estimated 24-month PFS, DOR, and OS rates in all patients were 57.4% (95% CI, 46.2-67), 66.4% (95% CI, 54.3-76), and 87.7% (95% CI, 78.3-93.2). Complete response rate and overall response rate were 68.1% (95% CI, 57.7-77.3) and 86.2% (95% CI, 77.5-92.4), respectively. No new safety signals or treatment-related deaths were reported. Low levels of tumor-infiltrating LAG3+CD3+ exhausted T-cells and higher baseline levels of naïve CD8+ T-cells were associated with improved outcomes. Tisagenlecleucel continued to demonstrate highly durable efficacy and a favorable safety profile in this extended follow-up of 29 months in patients with r/r FL enrolled in ELARA.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Durable response after tisagenlecleucel in adults with relapsed/refractory follicular lymphoma: ELARA trial update

Dreyling,

Fowler,

Dickinson

et al. 2024

Blood

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“…Among 124 treated patients, 36-month PFS and OS rates were 54.4% and 75%, respectively. Grade ≥ 3 cytokine release syndrome (CRS) occurred in 6% of the patients, and grade ≥ 3 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 15% [ 28 , 29 ]. A propensity score matching comparison between patients with R/R FL treated in the ZUMA-5 setting and patients treated with SOC therapies strongly favored axi-cel both in terms of PFS (HR 0.28, 95% CI: 0.17–0.45) and OS (HR 0.52, 95% CI: 0.28–0.95) [ 30 ].…”

Section: Upcoming Settingsmentioning

confidence: 99%

“…Patients experiencing progression of the disease within 24 months from first-line therapy (POD24) are still at increased risk of treatment failure after CAR-T cells and represent one of the major unmet clinical needs in the FL setting [ 29 , 31 ]. Indeed, the currently recruiting ZUMA-22 trial aims to compare axi-cel with SOC in the setting of high-risk R/R FL, i.e., patients failing at least one line of therapy if they experienced POD24 or otherwise after at least two lines [ 34 ].…”

Section: Upcoming Settingsmentioning

confidence: 99%

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Chimeric Antigen Receptor-T Cell Therapy for Lymphoma: New Settings and Future Directions

Benevolo Savelli,

Clerico,

Botto

et al. 2023

Cancers

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In the last decade, anti-CD19 CAR-T cell therapy has led to a treatment paradigm shift for B-cell non-Hodgkin lymphomas, first with the approval for relapsed/refractory (R/R) large B-cell lymphomas and subsequently for R/R mantle cell and follicular lymphoma. Many efforts are continuously being made to extend the therapeutic setting in the lymphoma field. Several reports are supporting the safety and efficacy of CAR-T cells in patients with central nervous system disease involvement. Anti-CD30 CAR-T cells for the treatment of Hodgkin lymphoma are in development and early studies looking for the optimal target for T-cell malignancies are ongoing. Anti-CD19/CD20 and CD19/CD22 dual targeting CAR-T cells are under investigation in order to increase anti-lymphoma activity and overcome tumor immune escape. Allogeneic CAR product engineering is on the way, representing a rapidly accessible ‘off-the-shelf’ and potentially more fit product. In the present manuscript, we will focus on recent advances in CAR-T cell therapy for lymphomas, including new settings and future perspectives in the field, reviewing data reported in literature in the last decade up to October 2023.

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Efficacy and safety of bendamustine‐containing bridging therapy in R/R LBCL patients receiving CD19 CAR T‐cells

Iacoboni,

Sánchez‐Salinas,

Rejeski

et al. 2024

HemaSphere

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Bridging therapy (BT) after leukapheresis is required in most relapsed/refractory (R/R) large B‐cell lymphoma (LBCL) patients receiving chimeric antigen receptor (CAR) T cells. Bendamustine‐containing regimens are a potential BT option. We aimed to assess if this agent had a negative impact on CAR‐T outcomes when it was administered as BT. We included R/R LBCL patients from six centers who received systemic BT after leukapheresis from February 2019 to September 2022; patients who only received steroids or had pre‐apheresis bendamustine exposure were excluded. Patients were divided into two BT groups, with and without bendamustine. Separate safety and efficacy analyses were carried out for axi‐cel and tisa‐cel. Of 243 patients who received BT, bendamustine (benda) was included in 62 (26%). There was a higher rate of BT progressors in the non‐benda group (62% vs. 45%, p = 0.02). Concerning CAR‐T efficacy, complete responses were comparable for benda versus non‐benda BT cohorts with axi‐cel (70% vs. 53%, p = 0.12) and tisa‐cel (44% vs. 36%, p = 0.70). Also, 12‐month progression‐free and overall survival were not significantly different between BT groups with axi‐cel (56% vs. 43% and 71% vs. 63%) and tisa‐cel (25% vs. 26% and 52% vs. 48%); there were no differences when BT response was considered. CAR T‐cell expansion for each construct was similar between BT groups. Regarding safety, CRS G ≥3 (6% vs. 6%, p = 0.79), ICANS G ≥3 (15% vs. 17%, p = 0.68), severe infections, and neutropenia post‐infusion were comparable among BT regimens. BT with bendamustine‐containing regimens is safe for patients requiring disease control during CAR T‐cell manufacturing.

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3-Year Follow-up Analysis of ZUMA-5: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory (R/R) Indolent Non-Hodgkin Lymphoma (iNHL)

Cited by 17 publications

References 0 publications

Durable response after tisagenlecleucel in adults with relapsed/refractory follicular lymphoma: ELARA trial update

Durable response after tisagenlecleucel in adults with relapsed/refractory follicular lymphoma: ELARA trial update

Chimeric Antigen Receptor-T Cell Therapy for Lymphoma: New Settings and Future Directions

Efficacy and safety of bendamustine‐containing bridging therapy in R/R LBCL patients receiving CD19 CAR T‐cells

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