ZUMA-7: A phase 3 randomized trial of axicabtagene ciloleucel (Axi-Cel) versus standard-of-care (SOC) therapy in patients with relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL).

Oluwole, Olalekan O.; Bishop, Michael; Gisselbrecht, Christian; Gordon, Leo I.; Kersten, Marie José; Maloney, David G.; Schmitz, Norbert; Barrigón, María Dolores Caballero; Kuruvilla, John; Song, Kevin; Jacobson, Caron A.; Nastoupil, Loretta J.; Riedell, Peter A.; Jiang, Yizhou; Rossi, John M.; Lee, Lillian; Cheng, Paul; Locke, Frederick L.

doi:10.1200/jco.2018.36.15_suppl.tps7585

Cited by 21 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…B-cell aplasia and hypogammaglobulinemia are attributed to on-target CD19 B-cell depletion, and notably most patients enrolling on CAR T-cell trials are hypogammaglobulinemic at baseline due to extensive prior lymphoma-directed therapies. Other cytopenias including neutropenia, lymphopenia, anemia, and thrombocytopenia may be secondary to lymphodepleting chemotherapy but have also been reported in the absence of conditioning and likely denote cytokine-mediated inflammatory marrow suppression [34] . Management of prolonged cytopenias is supportive until count recovery occurs.…”

Section: Other Car T-associated Toxicitiesmentioning

confidence: 99%

CAR T-Cell therapies in lymphoma: current landscape, ongoing investigations, and future directions

Haydu¹,

Abramson²

2021

JCMT

View full text Add to dashboard Cite

Chimeric antigen receptor (CAR) T-cell therapy has significantly improved outcomes for patients with relapsed/refractory large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma, with multiple FDAapproved CAR T products now commercially available. Ongoing studies seek to move CAR T-cells to earlier lines of therapy and to characterize the efficacy and safety of CAR T-cell approaches in additional lymphoma histologies including relapsed/refractory follicular lymphoma and chronic lymphocytic leukemia. Other areas of active research address CAR T in combination with other lymphoma-directed therapies, and mechanisms of CAR T resistance. This review focuses on the FDA-approved anti-CD19 CAR T products for B-cell lymphomas, management of CAR T-cell-associated toxicities, approaches to bridging therapy, and ongoing clinical trials and future research directions across a broad range of lymphoma histologies.

show abstract

Section: Other Car T-associated Toxicitiesmentioning

confidence: 99%

CAR T-Cell therapies in lymphoma: current landscape, ongoing investigations, and future directions

Haydu¹,

Abramson²

2021

JCMT

View full text Add to dashboard Cite

show abstract

“…Sixty-nine percent of the cohort experienced ICANS, including 25% grade ≥ 3. One-third of the patients received corticosteroids [5,19]. Locke et al reported that the presence of CCR7 + CD45RA + T-cells in the product correlated with efficacy in the ZUMA-1 trial [20].…”

Section: An Earlier Use Of Car T-cells In Therapeutic Strategies For Dlbclmentioning

confidence: 99%

T-cell Redirecting Therapies for the Treatment of B-cell Lymphomas: Recent Advances

Messéant¹,

Houot²,

Manson³

2021

Cancers

View full text Add to dashboard Cite

T-cell specificity can be redirected against tumor antigens either ex vivo using engineered chimeric antigen receptor (CAR) T-cells or in vivo by bridging natural T-cells and tumor cells with bispecific T-cell engager (TCE) antibodies. Currently, four CAR T-cells have been approved by the FDA for the treatment of B-cell lymphomas, including diffuse large B cell lymphomas (DLBCL), mantle cell lymphoma (MCL), and follicular lymphoma (FL). No TCE have yet been approved for the treatment of B-cell lymphomas. However, at least four of them are in clinical development and show promising activity. Here, we review the most recent advances of CAR T-cells and TCE in the treatment of B-cell lymphomas.

show abstract

“…One clinically relevant question is whether CART therapy could replace high dose chemotherapy and ASCT in R/R DLBCL. ZUMA-7 (NCT03391466) and BELINDA (NCT03570892) are phase 3 studies in which patients with aggressive B-cell lymphoma and either refractory disease or relapse following primary therapy are randomized to receive anti-CD19 CART therapy or high dose cytotoxic therapy and ASCT [57,58]. As salvage chemotherapy and ASCT can cure up to 50% of patients, the rates of cure with CAR-T therapy would need to be significantly more to justify the current costs of this therapy.…”

Section: Clinical Perspectives On Future Cart Use In Other Indicationsmentioning

confidence: 99%

Potentials, challenges and future of chimeric antigen receptor T-cell therapy in non-Hodgkin lymphomas

et al. 2020

View full text Add to dashboard Cite

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype. Disease progression or relapse following frontline chemoimmunotherapy, largely in the form of standard R-CHOP, occurs in 30-40% patients. Relapsed/refractory (R/R) DLBCL represents a major unmet medical need. In particular, patients with primary refractory disease or those whose lymphoma relapses after autologous stem cell transplantation have historically had poor outcomes. Material and methods: Chimeric antigen receptor T-cell (CART) therapy is a promising novel treatment with curative potential in this setting. CART is based on ex vivo genetic modification of autologous T-cells to express chimeric receptors targeting antigens highly expressed in tumors such as CD19 in DLBCL. After lymphocyte-depleting therapy, patients are infused with CARTs that expand in vivo and target CD19-positive lymphoma cells. Results: In initial phase I-II trials, investigators have demonstrated complete responses in 40-50% of patients with R/R DLBCL, resulting in durable remission approaching 3 years of follow-up in most of these patients without further treatment. The logistics of delivery are complex as cell products require timely long-distance transfer between hospitals and production facilities. The unique toxicity profile of CARTs, including the risk of fatal immunological and neurologic events, also requires specific hospital wide management approaches and education. The substantial direct and indirect costs of CART will limit access even in countries with well resourced health care systems. Conclusions: While only two products are commercially available at present, further approvals in coming years appear likely. Future directions include CARTs with reactivity to tumor antigens other than CD19 and products targeting multiple tumor antigens to overcome resistance. The availability of CART has altered the current treatment algorithm for R/R DLBCL, and indications will likely expand to earlier lines of therapy and other hematologic malignancies.

show abstract

ZUMA-7: A phase 3 randomized trial of axicabtagene ciloleucel (Axi-Cel) versus standard-of-care (SOC) therapy in patients with relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL).

Cited by 21 publications

References 0 publications

CAR T-Cell therapies in lymphoma: current landscape, ongoing investigations, and future directions

CAR T-Cell therapies in lymphoma: current landscape, ongoing investigations, and future directions

T-cell Redirecting Therapies for the Treatment of B-cell Lymphomas: Recent Advances

Potentials, challenges and future of chimeric antigen receptor T-cell therapy in non-Hodgkin lymphomas

Contact Info

Product

Resources

About