Burkitt lymphoma or leukemia (BL) is a highly aggressive non-Hodgkin lymphoma. Older age (over 60 years old) and the presence of high-risk factors (such as abdominal mass, high levels of the serum lactic dehydrogenase, Ann Arbor stage II-IV and so on) usually predict a poorer outcome. Chimeric antigen receptor T cells (CART) have achieved remarkable success in the treatment of B-cell leukemia and lymphoma. Here, for the first time, we report a 61-year-old, high-risk BL patient with autologous stem cell transplantation (ASCT) bridging therapy prior to CART as consolidation therapy. Our findings demonstrate that the combination of ASCT and CART for BL is safe and feasible.

UNASSIGNED: Chimeric antigen receptor (CAR) T-cell therapy is a promising treatment option for patients with refractory hematological malignancies. However, its efficacy in glioblastoma remains unclear. Here, we performed a systematic review to summarize the safety and efficacy of CAR T-cell therapy in glioblastoma.
UNASSIGNED: The PubMed, EMBASE, and Cochrane databases were searched to identify articles published before June 30, 2021 describing the use of CAR T-cell therapy in glioblastoma. Information on the toxicity of CAR T-cell therapy was summarized. The pooled objective response rate (ORR) and overall survival (OS) of patients who underwent CAR T-cell therapy were estimated using a random-effects model with an inverse-variance weighting model and quantile estimation method, respectively.
UNASSIGNED: Of 397 articles identified, eight studies including 63 patients with recurrent glioblastoma treated with various CAR T-cell regimens were included in the analysis. Six (9.5%) patients developed cytokine release syndrome (grade ≤2), and 16 (25.4%) experienced non-critical neurological events. The pooled ORR was 5.1% (95% confidence interval [CI], 0.0-10.4; I 2 = 0.05%), and the pooled median OS was 8.1 months (95% CI, 6.7-9.5; I 2 = 0.00%).
UNASSIGNED: Although CAR T-cell therapy is a relatively safe therapeutic option in patients with glioblastoma, it shows marginal efficacy, suggesting that further research is necessary for its translation into clinical practice for the treatment of recurrent glioblastoma.

The objective of this review was to identify sources of variability in cost-effectiveness analyses of chimeric antigen receptor T-cell (CAR-T) therapies, tisagenlecleucel and axicabtagene ciloleucel, evaluated by health technology assessment (HTA) agencies, focusing on young compared with older patients.
HTA evaluations in pediatric acute lymphoblastic leukemia (ALL) and adult diffuse large B-cell lymphoma (DLBCL) were included from Australia, Canada, England, Norway, and the United States. Key clinical evidence, economic approach, and outcomes (costs, quality-adjusted life-years [QALYs] and incremental cost-effectiveness ratios) were summarized.
Fourteen HTA evaluations were identified (5 ALL, 9 DLBCL [4 tisagenlecleucel, 5 axicabtagene]). Analyses were naive comparisons of prospective single-arm studies for the CAR-Ts with retrospective cohort studies for the comparators. Key clinical evidence and economic model approaches were generally consistent by CAR-T and indication, although outcomes varied. Notably, incremental QALYs varied substantially in ALL (3.67-10.6 QALYs gained), whereas variation in DLBCL was less (1.21-1.97 [tisagenlecleucel], 1.97-3.40 [axicabtagene]). Discounting of costs and outcomes varied, with the highest QALYs generated for tisagenlecleucel in ALL (10.95) associated with the lowest discount rate (1.5%) and vice versa (4.97 QALYs; 5% discount rate). The approach to extrapolation of overall survival data varied, even where the same empirical data were used.
Modeled, long-term treatment benefit in young patients may be associated with greater uncertainty compared with adults because of potential life-long benefits with cell and gene therapies. This reflects the methodological challenges identified by HTA agencies associated with single-arm, short-term studies.

Patients with postransplant lymphoproliferative disease (PTLD) who are refractory to rituximab-based regimens have extremely poor prognosis. Data is lacking in the setting of solid organ transplantation (SOT)-related PTLD treated with chimeric antigen receptor T-cell (CAR-T) therapy. Moreover, limited information is available on the influence of concomitant immunosuppressive drugs on CAR-T function. Here, we describe the clinical outcome in one PTLD patient and propose a strategy for tailoring immunosuppressive treatment and organ monitoring in patients with kidney allografts after CAR-T infusion. This report also reviews the limited published data in the setting of SOT-related PTLD treated with CAR-T, which appears to be a feasible treatment in this clinical scenario, without severe toxicity and capable of inducing sustained responses. A noteworthy finding is that in most reported cases patients underwent complete or partial discontinuation of immunosuppressive drugs, with only one documented case of allograft rejection.

Extramedullary multiple myeloma (EMM) is an aggressive sub-entity of multiple myeloma (MM). Despite an excellent improvement in survival for most patients with MM over recent decades, the overall survival (OS) of patients with EMM was usually not longer than 3 years. Standard treatment for patients with EMM has not been established, and their management is particularly challenging. We presented a heavily pretreated young patient with relapsed EMM and refractoriness to a proteasome inhibitor (PI; bortezomib), a next-generation PI (ixazomib), immunomodulatory drugs (IMiDs; lenalidomide), autologous hematopoietic stem cell transplantation (ASCT), and monoclonal antibody (directed against CD38: daratumumab) and indicated that myeloablative haploidentical hematopoietic stem cell transplantation (haploidentical-HSCT) as a salvage treatment of relapse after a chimeric antigen receptor (CAR)-T cell therapy that targeted B-cell maturation antigen (BCMA) (NCT04650724) is feasible. Taken together of the contemporary literature, the promising results on the effect of anti-BCMA CAR-T cell therapy and allogeneic HSCT might present a proof-of-principle for patients with EMM, and therefore, patients with the disease need to be included in future studies.

Introduction: Immunotherapy has revolutionized the treatment of cancer. Antibodies, antibody drug conjugates, and bispecific antibodies have improved outcomes in various cancers especially lymphomas. Chimeric antigen receptor T cell (CAR-T) is a step forward in the immunotherapy paradigm for the treatment of Lymphomas. Recently, two CAR-T products, Tisagenlecleucel and Axicabtagene ciloleucel, were approved by the US FDA. While it is exciting to have such novel treatment available, the challenges of production, administration, related toxicity, and cost remain. Specific toxicities related to CAR-T like Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) could be fatal and need close monitoring and prompt treatment to avoid mortality and improve efficacy of the treatment. Areas covered: In this article, the authors discuss receptor constructs, administration, toxicities, efficacy and reimbursement of CAR-T treatment. Expert opinion: Since approval of CAR-T treatment, cost of therapy and reimbursement have been a big challenge in implementation of CAR-T. This has triggered cost-effective analysis and nationwide discussions about the reimbursement process of such treatment. In spite of these challenges, CAR-T treatment is a huge step forward with a very bright future. Novel CAR-T targeting a variety of antigens in different cancers seems promising in near future.