Tecartus (brexucabtagene autoleucel)

Introduction: Brexucabtagene autoleucel (brexu cel) is a CD19-targeted chimeric antigen receptor (CAR) T cell therapy approved for the treatment of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL)...No differences were observed with respect to sex, TP53 mutation status, prior inotuzumab (ino) or blinatumomab (blina) exposure, disease burden prior to CAR, or development of any cytokine release syndrome (CRS) or any neurotoxicity with brexu cel... In a large real-world cohort of adults with R/R B-ALL infused with brexu cel, we identified practice variation regarding the use of consolidative HCT. Among brexu cel recipients who entered an MRD- CR, we identified ClonoSeq NGS MRD negativity as a novel predictive factor of favorable oncologic outcomes, even without a consolidative HCT. Similar results have been obtained in pediatric ALL patietns ftreated with 41BB-based tisagenleucleucel (Pulsipher et al., Blood Cancer Discovery 2022).

Secondary malignancies seem more frequent after CAR-T therapies. More studies are needed to assess potential long-term toxicities of CAR-T cell therapies including the frequency of secondary myeloid malignancies.

P1/2, N=95, Active, not recruiting, Kite, A Gilead Company | Trial primary completion date: Mar 2026 --> Sep 2024

P2, N=60, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Not yet recruiting --> Recruiting

P1/2, N=95, Active, not recruiting, Kite, A Gilead Company | Trial primary completion date: Sep 2024 --> Mar 2026

P2, N=60, Not yet recruiting, H. Lee Moffitt Cancer Center and Research Institute

P2, N=90, Active, not recruiting, Kite, A Gilead Company | Trial completion date: Oct 2038 --> Jun 2025 | Trial primary completion date: Nov 2023 --> Nov 2024

P2, N=19, Active, not recruiting, Kite, A Gilead Company | Recruiting --> Active, not recruiting | N=90 --> 19

P2, N=27, Recruiting, Beijing Cancer Hospital; Fosun Kite Biotechnology Co., Ltd. | Not yet recruiting --> Recruiting

P2, N=28, Recruiting, Peking University People's Hospital; Fosun Kite Biotechnology Co., Ltd | Not yet recruiting --> Recruiting

P1/2, N=40, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

P2, N=150, Recruiting, Christian Schmidt, MD

P1/2, N=95, Active, not recruiting, Kite, A Gilead Company | Recruiting --> Active, not recruiting | Trial completion date: Aug 2027 --> Mar 2026 | Trial primary completion date: Dec 2025 --> Sep 2024

Prior therapy included blinatumomab (94%), inotuzumab (88%), allo-SCT (24%)...Tocilizumab was needed in 15 pts (44%), dexamethasone 7 pts (21%), and 2 pts needed ICU care... Use of brexu-cel in pts with low tumor burden is associated with low rates of G3-4 CRS/ICANS. We noted CART expansion in pts with no morphologic disease prior to LD. Prospective trials are planned to assess role of CART in low tumor burden setting, including MRD+ and as consolidation strategy.

P2, N=40, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

Among possible determinants of CD4+ T cell recovery, we recognized infusion of a 4-1BB product (tisagenlecleucel, TSA) in comparison with a CD28 (axicabtagene/brexucabtagene, AXI/BRX) (hazard ratio [HR] [95% CI]: 5.79 [1.16-24.12] p = 0.016). We conclude that a faster CAR- CD4+ T cell recovery is associated with TSA as compared to AXI/BRX. Month-1 CAR- CD4+ T cell subset recovery could represent a "red flag" for CAR-T cell therapy failure in DLBCL patients.

P2, N=90, Recruiting, Kite, A Gilead Company | Trial completion date: Dec 2027 --> Mar 2025 | Trial primary completion date: Dec 2027 --> Mar 2025

P2, N=700, Enrolling by invitation, Kite, A Gilead Company | Trial completion date: Mar 2041 --> Dec 2040 | Trial primary completion date: Mar 2041 --> Dec 2040

Findings suggest that brexu-cel may offer clinically and statistically significant benefits regarding objective response, complete response, and progression-free survival compared to pirtobrutinib among patients with R/R MCL after prior cBTKi therapy. Given the short follow-up and high degree of censoring in BRUIN, an analysis incorporating updated BRUIN data may provide more definitive overall survival results.

P=N/A, N=144, Active, not recruiting, Masonic Cancer Center, University of Minnesota | Recruiting --> Active, not recruiting | N=240 --> 144 | Trial primary completion date: Jun 2028 --> Feb 2024

P1/2, N=40, Not yet recruiting, M.D. Anderson Cancer Center

With the simultaneous detection of the CAR-T cells and the B cell malignancy in patient peripheral blood, the HDSCA-HemeCAR workflow may be considered for risk monitoring and patient management.

P1, N=20, Recruiting, Stanford University | Phase classification: P1b --> P1

P2, N=21, Recruiting, Kite, A Gilead Company

Brexucabtagene autoleucel CAR-T therapy is highly efficacious in overcoming resistance to Bruton's tyrosine kinase inhibitors (BTKi) in mantle cell lymphoma...Pharmaceutical co-targeting of HSP90 and CDK9 synergistically diminished MYC activity, leading to potent anti-MCL activity. Collectively, our study revealed that HSP90-MYC-CDK9 network is the primary driving force of therapeutic resistance.

P2, N=40, Not yet recruiting, M.D. Anderson Cancer Center

P1/2, N=116, Recruiting, Kite, A Gilead Company

P2, N=60, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Nov 2026 --> Nov 2028

P2, N=90, Active, not recruiting, Kite, A Gilead Company | Trial primary completion date: Jul 2024 --> Nov 2023

P2, N=28, Not yet recruiting, Peking University People's Hospital; Fosun Kite Biotechnology Co., Ltd

Introduction: Fludarabine and cyclophosphamide (Flu/Cy) lymphodepletion (LD) prior to chimeric antigen T-cell (CAR T) infusion favorably impacts CAR T expansion and efficacy...Three deaths (2 Cla/Cy) occurred before day 100, all due to refractory fungemia post anakinra... Cla/Cy LD prior to brexu-cel is feasible in ALL and MCL patients with comparable efficacy. Toxicity rates including CRS, ICANS and early infections were similar to those seen with Flu/Cy, but there was a trend towards earlier recovery of neutrophils, B-, and T-cells with Cla/Cy. The trend was demonstrable even in patients at high risk of prolonged post-CAR T neutropenia as identified by the HS.

While many therapies are under investigation including the addition of a tyrosine kinase inhibitor or ruxolitinib to conventional chemotherapy, a standardized and molecularly-based approach to treating patients with Ph-like ALL is not yet defined. There also remain questions about the efficacy of integrating inotuzumab ozogamicin or blinatumomab into first-line therapy for these patients...1 patient received Car T cell therapy with Brexucabtagene autoleucel following relapse after allogeneic stem cell transplant... We identified 9 patients who met inclusion criteria. All 9 patients self-identified as either ‘American Indian or Alaska Native’ or ‘Hispanic or Latino. ‘ The median age at diagnosis was 34 and the mean BMI at diagnosis was 34.

P2, N=60, Recruiting, H. Lee Moffitt Cancer Center and Research Institute

P1/2, N=125, Completed, Kite, A Gilead Company | Active, not recruiting --> Completed | Trial completion date: Nov 2034 --> Nov 2023

The main goals of the symposium are: to share the benefits of Yescarta in 3/2L of LBDCL in the elderly patient setting share the benefits of Tecartus in MCL, a disease with major incidence in older patients. Target audience: Hematologists, geriatricians, nurses and other healthcare professionals in contact with geriatric cancer patients.

While acknowledging the inherent limitations of an unanchored indirect comparison, our findings suggest that brexu-cel offers clinically and statistically significant efficacy benefits in terms of ORR, CR, and PFS compared to pirtobrutinib in patients with R/R MCL after prior cBTKi therapy. Both treatments were not statistically different in terms of OS and DOR although the estimated hazard ratios indicated a favorable trend for brexu-cel; however, given the relatively shorter follow-up and the high degree of censoring in BRUIN, an updated analysis incorporating longer follow-up data with more events from BRUIN could provide more reliable results. Although efforts were made to ensure a robust approach to the selection of prognostic factors for inclusion in the model, the possibility of some residual confounding variables cannot be completely ruled out.

Background: Cytokine release syndrome (CRS) is a potentially life-threatening, supraphysiologic response following immunotherapy resulting in the activation or engagement of endogenous or infused T cells and/or other immune effector cells. Table 1 summarizes data by indication. Incidence of CRS ranged from 56% (104/185) in DLBCL to 72% (66/92) in MCL. Excluding categories with small numbers of cases (<15), CRS incidence also varied by individual CAR-T therapy and underlying indication and ranged from 35% for idecabtagene vicleucel in MM to 73% for brexucabtagene autoleucel in MCL.

Preceding CAR-T, median number of treatments was 3 (range 1-9), all patients had prior Rituximab and Ibrutinib, 62 patients (56%) had received autologous stem cell transplantation (SCT) and 11 patients had received an allogeneic SCT. 111 patients have been identified: median age at diagnosis was 64.3 years (range 42.3-79.5; 19/99 patients ≥ 70), 18% female (not known (nk) 2.7%); ethnicity 66.7% Caucasian (nk 30.6%). Disease characteristics: 80/88 had stage 3/4 (91%), histology was classical in 34/57 cases (60%) and blastoid in 19/57 (33%), respectively. MIPI score was low 14/53 (26%), intermediate 17 (32%), high 21 (40%).

Pts received a median of 4 prior lines of therapy (range 1-13); 46% had prior inotuzumab and 58% had prior blinatumomab...Treatment for CRS and/or ICANS consisted mainly of tocilizumab (67%) and corticosteroids (51%)...Updated data with longer follow-up will be reported at the time of presentation. *First and second authors are equal contributors

ALC data for 84 pts who received CD19 CAR-T (77 pts with axicabtagene ciloleucel and 7 pts with brexucabtagene autoleucel) for non-Hodgkin lymphoma (NHL) were included as a comparison...Furthermore, ALC dynamics differed by BCMA CAR-T product, with cilta-cel exhibiting later CRS with higher max-ALC peaking at a later day when compared to ide-cel. Furthermore, higher max-ALC and absolute ALC increase were associated with deeper response (VGPR/CR) and sustainable response on follow up. Our findings suggest that peripheral lymphocytosis after CAR-T is disease specific (NHL vs MM) and post CAR-T lymphocytosis in peripheral blood is a potential biomarker for clinical outcomes and toxicity.

Similarly, with brexucabtagene autoleucel (brexu-cel), ICANS also occurred in approximately 60% with ≥ G3 occurring in 26-31% of patients...Tocilizumab (8 mg/kg) was administered to 11 patients (73.3%) with the median number of doses being 1 (range 1 to 4)...One patient with Richter's had progressive disease at day 30, 4 patients had partial remission, and 10 patients had a complete remission for an ORR of 93%. Conclusions Preliminary results show that simvastatin and intrathecal dexamethasone appear to be feasible, safe, and effective in reducing the incidence and severity of ICANS in patients receiving axi-cel and brexu-cel.

INTRODUCTION: Over 40% of patients with mantle cell lymphoma (MCL) will progress within 1 year after treatment with brexucabtagene autoleucel (Brexu-cel)(Michael Wang et al... Evidence from the ZUMA-2 study and our study highlights the significance of early post-CAR-T MRD as an independent prognostic marker for predicting disease recurrence and durable remissions in MCL. Combining MRD measurements with PET-CT at months 1, 3, and 6 after CAR-T therapy can effectively identify high-risk patients for disease progression, offering promising potential to improve outcomes in MCL.