scholarly journals Safety and efficacy of axicabtagene ciloleucel in refractory large B-cell lymphomas

2020 ◽  
Vol 11 ◽  
pp. 204062072090289 ◽  
Author(s):  
Peter A. Riedell ◽  
Michael R. Bishop
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
B Cell Lymphoma ◽  
B Cell Lymphomas ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Large B Cell

Aggressive large B-cell lymphomas represent a diverse population of diseases that are typically treated with anti-CD20 based immunochemotherapy. While this treatment is effective for a large proportion of patients, those that become refractory to induction therapy or experience disease relapse suffer an inferior overall prognosis, and novel treatment options are needed. Adoptive T-cell immunotherapy in the form of chimeric antigen receptor (CAR) T-cell therapy is one of the most revolutionary breakthroughs in the past several decades for the treatment of relapsed/refractory aggressive large B-cell lymphomas. Based on data from the pivotal ZUMA-1 study, axicabtagene ciloleucel (axi-cel) became the first-in-class anti-CD19 directed CAR T-cell therapy approved for patients with diffuse large B-cell lymphoma and other aggressive B-cell lymphoma variants. In this review, we provide an overview of CAR T-cell therapy, including its biology, manufacturing, and treatment course. In addition, we highlight the available efficacy data, review pertinent safety concerns, including cytokine release syndrome and neurologic toxicity, as well as provide an overview of emerging therapeutic strategies in the cellular therapy arena.

scholarly journals Polatuzumab vedotin as a salvage and bridging treatment in relapsed or refractory large B-cell lymphomas

2021 ◽  
Vol 5 (13) ◽  
pp. 2707-2716
Author(s):  
Nora Liebers ◽  
Johannes Duell ◽  
Donnacha Fitzgerald ◽  
Andrea Kerkhoff ◽  
Daniel Noerenberg ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Overall Response ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Large B Cell

The antibody-drug conjugate polatuzumab vedotin (pola) has recently been approved in combination with bendamustine and rituximab (pola-BR) for patients with refractory or relapsed (r/r) large B-cell lymphoma (LBCL). To investigate the efficacy of pola-BR in a real-world setting, we retrospectively analyzed 105 patients with LBCL who were treated in 26 German centers under the national compassionate use program. Fifty-four patients received pola as a salvage treatment and 51 patients were treated with pola with the intention to bridge to chimeric antigen receptor (CAR) T-cell therapy (n = 41) or allogeneic hematopoietic cell transplantation (n = 10). Notably, patients in the salvage and bridging cohort had received a median of 3 prior treatment lines. In the salvage cohort, the best overall response rate was 48.1%. The 6-month progression-free survival and overall survival (OS) was 27.7% and 49.6%, respectively. In the bridging cohort, 51.2% of patients could be successfully bridged with pola to the intended CAR T-cell therapy. The combination of pola bridging and successful CAR T-cell therapy resulted in a 6-month OS of 77.9% calculated from pola initiation. Pola vedotin-rituximab without a chemotherapy backbone demonstrated encouraging overall response rates up to 40%, highlighting both an appropriate alternative for patients unsuitable for chemotherapy and a new treatment option for bridging before leukapheresis in patients intended for CAR T-cell therapy. Furthermore, 7 of 12 patients with previous failure of CAR T-cell therapy responded to a pola-containing regimen. These findings suggest that pola may serve as effective salvage and bridging treatment of r/r LBCL patients.

scholarly journals Outcomes of patients with large B‐cell lymphomas and progressive disease following CD19‐specific CAR T‐cell therapy

2019 ◽  
Vol 94 (8) ◽  
Author(s):  
Victor A. Chow ◽  
Ajay K. Gopal ◽  
David G. Maloney ◽  
Cameron J. Turtle ◽  
Stephen D. Smith ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Progressive Disease ◽  
B Cell Lymphomas ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Large B Cell

scholarly journals Influence of TP53 Mutation on Survival of Diffuse Large B-Cell Lymphoma in the CAR T-Cell Era

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5592
Author(s):  
Edit Porpaczy ◽  
Philipp Wohlfarth ◽  
Oliver Königsbrügge ◽  
Werner Rabitsch ◽  
Cathrin Skrabs ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Tp53 Mutation ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Refractory/relapsed diffuse large B-cell lymphoma (DLBCL) is associated with poor outcome. The clinical behavior and genetic landscape of DLBCL is heterogeneous and still not fully understood. TP53 mutations in DLBCL have been identified as markers of poor prognosis and are often associated with therapeutic resistance. Chimeric antigen receptor T-cell therapy is an innovative therapeutic concept and represents a game-changing therapeutic option by supporting the patient’s own immune system to kill the tumor cells. We investigated the impact of TP53 mutations on the overall survival of refractory/relapsed DLBCL patients treated with comparable numbers of therapy lines. The minimum number of therapy lines was 2 (median 4), including either anti-CD19 CAR T-cell therapy or conventional salvage therapy. A total of 170 patients with DLBCL and high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 rearrangements (DHL/THL), diagnosed and treated in our hospital between 2000 and 2021, were included. Twenty-nine of them received CAR T-cell therapy. TP53 mutations were found in 10/29 (35%) and 31/141 (22%) of patients in the CAR T-cell and conventional groups, respectively. Among the 141 patients not treated with CAR T cells, TP53 mutation was an independent prognostic factor for overall survival (OS) (median 12 months with TP53 vs. not reached without TP53 mutation, p < 0.005), but in the CAR T cell treated group, this significance could not be shown (median OS 30 vs. 120 months, p = 0.263). The findings from this monocentric retrospective study indicate that TP53 mutation status does not seem to affect outcomes in DLBCL patients treated with CAR T-cell therapy. Detailed evaluation in large cohorts is warranted.

CD19-DIRECTED CAR T CELL THERAPY (CTL019) FOR RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL AND FOLLICULAR LYMPHOMAS: FOUR YEAR OUTCOMES

2019 ◽  
Vol 37 ◽  
pp. 137-138 ◽  
Author(s):  
E.A. Chong ◽  
J. Svoboda ◽  
S.D. Nasta ◽  
D.J. Landsburg ◽  
N. Winchell ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Follicular Lymphomas ◽  
Large B Cell

scholarly journals Impact of Increasing Wait Times on Overall Mortality of Chimeric Antigen Receptor T-Cell Therapy in Large B-Cell Lymphoma: A Discrete Event Simulation Model

2019 ◽  
pp. 1-9 ◽  
Author(s):  
Stephen Tully ◽  
Zeny Feng ◽  
Kelly Grindrod ◽  
Tom McFarlane ◽  
Kelvin K.W. Chan ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell Lymphoma ◽  
Wait Times ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Large B Cell Lymphoma ◽  
Car T Cell Therapy ◽  
Car T ◽  
Large B Cell

PURPOSE The development of chimeric antigen receptor (CAR) T cells has transformed oncology treatment, with the potential to cure certain cancers. Although shown to be effective in selected populations and studies, CAR T-cell technology requires considerable health care resources, which may lead to additional wait times to access this type of treatment in future. The objective of our study was to estimate the potential impact of increasing wait times on CAR T-cell therapy effectiveness compared with standard chemotherapy for patients with relapsed/refractory diffuse large B-cell lymphoma. METHODS A health system–level discrete event simulation model was developed to project the potential impact of wait times on CAR T-cell therapy for patients with relapsed/refractory diffuse large B-cell lymphoma. Waiting queues and health states related to treatment and clinical progression were implemented. Using data from the literature, we evaluated nine scenarios of using CAR T-cell therapy with wait times ranging from 1 to 9 months. The outcome of interest was 1-year all-cause mortality. RESULTS Increasing the wait time of receiving CAR T-cell therapy from 1 to 9 months increased the predicted 1-year mortality rate from 36.1% to 76.3%. Baseline 1-year mortality was 34.0% in patients receiving CAR T-cell therapy with no wait times and 75.1% in patients treated with chemotherapy. This resulted in an increased relative mortality rate of 6.2% to 124.5% over a 1- to 9-month wait time compared with no wait time. CONCLUSION We found that modest delays in CAR T-cell therapy significantly hinder its effectiveness. Because CAR T-cell therapy offers a potential cure, it is expected that the uptake rate will be substantially increased once the therapy is regularly funded by a health care system. Wait times may be prolonged if system resource availability does not match the demand. Strategies must be developed to minimize the impact of delays and reduce complications during waiting.

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