Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium

Abstract

PURPOSE Axicabtagene ciloleucel (axi-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory large B-cell lymphoma (LBCL) on the basis of the single-arm phase II ZUMA-1 trial, which showed best overall and complete response rates in infused patients of 83% and 58%, respectively. We report clinical outcomes with axi-cel in the standard-of-care (SOC) setting for the approved indication. PATIENTS AND METHODS Data were collected retrospectively from all patients with relapsed/refractory LBCL who underwent leukapheresis as of September 30, 2018, at 17 US institutions with the intent to receive SOC axi-cel. Toxicities were graded and managed according to each institution’s guidelines. Responses were assessed as per Lugano 2014 classification. RESULTS Of 298 patients who underwent leukapheresis, 275 (92%) received axi-cel therapy. Compared with the registrational ZUMA-1 trial, 129 patients (43%) in this SOC study would not have met ZUMA-1 eligibility criteria because of comorbidities at the time of leukapheresis. Among the axi-cel–treated patients, grade ≥ 3 cytokine release syndrome and neurotoxicity occurred in 7% and 31%, respectively. Nonrelapse mortality was 4.4%. Best overall and complete response rates in infused patients were 82% (95% CI, 77% to 86%) and 64% (95% CI, 58% to 69%), respectively. At a median follow-up of 12.9 months from the time of CAR T-cell infusion, median progression-free survival was 8.3 months (95% CI, 6.0 to15.1 months), and median overall survival was not reached. Patients with poor Eastern Cooperative Oncology Group performance status of 2-4 and elevated lactate dehydrogenase had shorter progression-free and overall survival on univariable and multivariable analysis. CONCLUSION The safety and efficacy of axi-cel in the SOC setting in patients with relapsed/refractory LBCL was comparable to the registrational ZUMA-1 trial.

Sequential therapy with inotuzumab ozogamicin, CD19 CAR T cells, and blinatumomab in an elderly patient with relapsed acute lymphoblastic leukemia

“…So far, data on CAR T cell therapy in older patients with B-precursor ALL and active CNS involvement are limited. In general, the observed CAR T cell-related toxicities such as cytokine release syndrome or neurologic toxicities in older patients seemed to be comparable in those seen in younger patients [11]. Our case report demonstrates efficacy and tolerability of CD19-directed CAR T cell therapy in an elderly patient with r/ r B-ALL.…”

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

“…Often oncologists address this dilemma with bridging therapy (BT; commonly referred to as therapy administered after apheresis and before CAR T-cell infusion), which may include steroids, chemotherapy, targeted therapy, or radiation therapy (RT). 5,6 However, the ZUMA-1 trial that led to axi-cel approval did not permit the administration of BT other than dexamethasone. 1 It is unclear if BT adversely affects outcome.…”

Assessment of CAR T Cell Frequencies in Axicabtagene Ciloleucel and Tisagenlecleucel Patients Using Duplex Quantitative PCR

“…Based on the data from the ELIANA (ALL) [ 1 ] and JULIET (diffuse large B cell lymphoma (DLBCL)) [ 10 ] as well as ZUMA-1 (DLBCL and primary mediastinal B-cell lymphoma (PMBCL)) [ 9 , 11 ] trials, two second-generation CD19-directed CART products, i.e., axicabtagene ciloleucel (axi-cel, Yescarta; CD28 costimulatory domain) and tisagenelecleucel (tisa-cel, Kymriah; 4-1BB costimulatory domain), have been approved. Both products have been adopted as standard of care within the labelled indications [ 12 , 13 , 14 , 15 ] and are being integrated into the clinical routine.…”