Matching-adjusted indirect treatment comparison of liso-cel versus axi-cel in relapsed or refractory large B cell lymphoma.

In the absence of randomized studies directly comparing chimeric antigen receptor T cell therapies, this study used matching-adjusted indirect comparisons (MAIC) to evaluate the comparative efficacy and safety of lisocabtagene maraleucel (liso-cel) versus axicabtagene ciloleucel (axi-cel) in patients with relapsed or refractory large B cell lymphoma (LBCL). Primary data sources included individual patient data from the TRANSCEND NHL 001 study (TRANSCEND [NCT02631044]; N = 256 for efficacy set, N = 269 for safety set) for liso-cel and summary-level data from the ZUMA-1 study (NCT02348216; N = 101 for efficacy set, N = 108 for safety set) for axi-cel. Inter-study differences in design, eligibility criteria, baseline characteristics, and outcomes were assessed and aligned to the extent feasible. Clinically relevant prognostic factors were adjusted in a stepwise fashion by ranked order. Since bridging therapy was allowed in TRANSCEND but not ZUMA-1, the initial efficacy and safety analyses included bridging therapy use as a matching factor (TRANSCEND patients who received bridging therapy were removed). Subsequent sensitivity analyses excluded this matching factor. The initial analysis showed similar MAIC-weighted efficacy outcomes between TRANSCEND and ZUMA-1 for overall and complete response rates (odds ratio [95% confidence interval (CI)], 1.40 [0.56-3.49] and 1.21 [0.56-2.64], respectively) and for overall survival and progression-free survival (hazard ratio [95% CI], 0.81 [0.44-1.49] and 0.95 [0.58-1.57], respectively). MAIC-weighted safety outcomes favored liso-cel, with significantly lower odds of all-grade and grade ≥ 3 cytokine release syndrome (odds ratio [95% CI], 0.03 [0.01-0.07] and 0.08 [0.01-0.67], respectively) and study-specific neurological events (0.16 [0.08-0.33] and 0.05 [0.02-0.15], respectively). Efficacy and safety outcomes remained similar in sensitivity analyses, which did not include use of bridging therapy as a matching factor. After matching and adjusting for clinically relevant prognostic factors, liso-cel demonstrated comparable efficacy and a more favorable safety profile compared with axi-cel in patients with third- or later-line relapsed or refractory LBCL. NCT02631044 and NCT02348216.

Maloney DG ，Kuruvilla J ，Liu FF ，Kostic A ，Kim Y ，Bonner A ，Zhang Y ，Fox CP ，Cartron G ... -  《Journal of Hematology & Oncology》

Matching-adjusted indirect comparison of axi-cel and liso-cel in relapsed or refractory large B-cell lymphoma.

Oluwole OO ，Chen JMH ，Chan K ，Patel AR ，Jansen JP ，Keeping S ，Zheng Y ，Snider JT ，Locke FL ... -  《-》

Cost-effectiveness of axicabtagene ciloleucel versus lisocabtagene maraleucel for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy in the US.

Oluwole OO ，Liu R ，Diakite I ，Feng C ，Patel A ，Nourhussein I ，Snider JT ，Locke FL ... -  《-》

Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study.

Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-cell product. We aimed to assess the activity and safety of liso-cel in patients with relapsed or refractory large B-cell lymphomas. We did a seamless design study at 14 cancer centres in the USA. We enrolled adult patients (aged ≥18 years) with relapsed or refractory large B-cell lymphomas. Eligible histological subgroups included diffuse large B-cell lymphoma, high-grade B-cell lymphoma with rearrangements of MYC and either BCL2, BCL6, or both (double-hit or triple-hit lymphoma), diffuse large B-cell lymphoma transformed from any indolent lymphoma, primary mediastinal B-cell lymphoma, and follicular lymphoma grade 3B. Patients were assigned to one of three target dose levels of liso-cel as they were sequentially tested in the trial (50 × 106 CAR+ T cells [one or two doses], 100 × 106 CAR+ T cells, and 150 × 106 CAR+ T cells), which were administered as a sequential infusion of two components (CD8+ and CD4+ CAR+ T cells) at equal target doses. Primary endpoints were adverse events, dose-limiting toxicities, and the objective response rate (assessed per Lugano criteria); endpoints were assessed by an independent review committee in the efficacy-evaluable set (comprising all patients who had confirmed PET-positive disease and received at least one dose of liso-cel). This trial is registered with ClinicalTrials.gov, NCT02631044. Between Jan 11, 2016, and July 5, 2019, 344 patients underwent leukapheresis for manufacture of CAR+ T cells (liso-cel), of whom 269 patients received at least one dose of liso-cel. Patients had received a median of three (range 1-8) previous lines of systemic treatment, with 260 (97%) patients having had at least two lines. 112 (42%) patients were aged 65 years or older, 181 (67%) had chemotherapy-refractory disease, and seven (3%) had secondary CNS involvement. Median follow-up for overall survival for all 344 patients who had leukapheresis was 18·8 months (95% CI 15·0-19·3). Overall safety and activity of liso-cel did not differ by dose level. The recommended target dose was 100 × 106 CAR+ T cells (50 × 106 CD8+ and 50 × 106 CD4+ CAR+ T cells). Of 256 patients included in the efficacy-evaluable set, an objective response was achieved by 186 (73%, 95% CI 66·8-78·0) patients and a complete response by 136 (53%, 46·8-59·4). The most common grade 3 or worse adverse events were neutropenia in 161 (60%) patients, anaemia in 101 (37%), and thrombocytopenia in 72 (27%). Cytokine release syndrome and neurological events occurred in 113 (42%) and 80 (30%) patients, respectively; grade 3 or worse cytokine release syndrome and neurological events occurred in six (2%) and 27 (10%) patients, respectively. Nine (6%) patients had a dose-limiting toxicity, including one patient who died from diffuse alveolar damage following a dose of 50 × 106 CAR+ T cells. Use of liso-cel resulted in a high objective response rate, with a low incidence of grade 3 or worse cytokine release syndrome and neurological events in patients with relapsed or refractory large B-cell lymphomas, including those with diverse histological subtypes and high-risk features. Liso-cel is under further evaluation at first relapse in large B-cell lymphomas and as a treatment for other relapsed or refractory B-cell malignancies. Juno Therapeutics, a Bristol-Myers Squibb Company.

Abramson JS ，Palomba ML ，Gordon LI ，Lunning MA ，Wang M ，Arnason J ，Mehta A ，Purev E ，Maloney DG ，Andreadis C ，Sehgal A ，Solomon SR ，Ghosh N ，Albertson TM ，Garcia J ，Kostic A ，Mallaney M ，Ogasawara K ，Newhall K ，Kim Y ，Li D ，Siddiqi T ... -  《-》

Network meta-analysis of CAR T-Cell therapy for the treatment of 3L+ R/R LBCL after using published comparative studies.

Oluwole OO ，Neelapu SS ，Ray MD ，Limbrick-Oldfield EH ，Wade SW ，Kanters S ，Patel AR ，Locke FL ... -  《-》