ASCO: Advances in T cell therapies for lymphomas

Two studies led by MD Anderson researchers explore advancements in CAR T cell therapy fornon-Hodgkin lymphomas。CAR T细胞疗法is commonly used to treat large B-cell lymphoma and follicular lymphoma, which are types of non-Hodgkin lymphomas, and ongoing research focuses on minimizing toxicities and improving effectiveness, leading to better therapeutic outcomes for patients. Initial results from both studies were shared at the临床肿瘤学会（ASCO）年会2020年美国社会。

Allogeneic CAR T cell therapy shows promise in first-in-human clinical trial (abstract 8002)

Autologous CAR T cell therapy, in which CAR T cells are engineered from a patient’s own T cells, is effective against advanced non-Hodgkin lymphomas, but often, creating the therapy can be logistically challenging. Allogeneic CAR T cell therapy, in which CAR T cells are manufactured from a healthy donor, addresses these challenges. Data from thePhase I ALPHA clinical trialfound that conditioning with ALLO-647, an anti-CD52 monoclonal antibody, followed by treatment with ALLO-501, an allogeneic anti-CD19 CAR T cell product, is safe and potentially effective against relapsed or refractory large B-cell lymphoma and follicular lymphoma.

移植物抗宿主病（GVHD）的风险中ALLO-501通过基因去除T细胞受体减少。进一步遗传修饰允许使用的ALLO-647，以选择性地延长的淋巴细胞缺失，这是降低注入患者的CAR T细胞之前正常淋巴细胞的数量的过程。由主机与ALLO-647延迟排斥ALLO-501 CAR的T细胞的这种选择性调节和改善它们的持久性。

At the time of data collection, 12 patients were enrolled in the clinical trial at six centers in the U.S., and nine patients were treated with ALLO-501 at three dose levels. The overall response rate was 78%, with three complete and four partial responses.

The most common Grade 3 or 4 adverse events were neutropenia (55.6%), leukopenia (33.3%) and anemia (22.2%). Two of the treated patients developed grade 1 or 2 cytokine release syndrome, which resolved within 72 hours without the use of tocilizumab or corticosteroids. To date, there have been no GVHD or dose-limiting toxicities.

“Although early, these findings will indicate that allogeneic CAR T cell therapy can be safe and induce significant responses in patients with relapsed or refractory B-cell non-Hodgkin lymphomas. Longer follow-up is needed to determine durability of the responses,” says lead authorSattva Neelapu, M.D., professor of淋巴瘤和骨髓瘤。“基于这些发现,注册正在进行中at higher doses of ALLO-647 conditioning and higher doses of ALLO-501.”

The clinical trial continues enrolling patients, and additional safety and efficacy data is being presented at the conference.See the abstract and co-authors here。

Early and prolonged use of corticosteroids can reduce the effectiveness of CAR T cell therapies (abstract 8011)

When severe side effects to CAR T cell therapy occur, corticosteroids are commonly prescribed to manage them. MD Anderson researchers examined whether corticosteroid therapy could affect the clinical efficacy of CAR T cell therapy, as well as whether the duration, dose or timing of corticosteroid treatment could impact clinical outcomes.

Their findings suggest that early and prolonged use of high-dose corticosteroids is associated with early disease progression and death in patients with大B细胞淋巴瘤(LBCL) who were treated with axi-cel, a type of CAR T cell therapy.

In a retrospective analysis of 100 patients with relapsed or refractory large B-cell lymphoma who were treated with standard of care axi-cel, researchers found that 60% of the patients had received corticosteroids to manage toxicities. The use of any dose of corticosteroids was associated with shorter progression-free survival (PFS), with those receiving corticosteroids having a median progression-free survival of six months versus nine months for those who did not receive steroids.

Further, the use of high-dose corticosteroids was significantly associated with shorter progression-free survival. Those receiving corticosteroids had a median progression-free survival of two months versus nine months for those who did not receive steroids. Prolonged use of corticosteroids, longer than 10 days, and earlier use of corticosteroids, in the first 7 days following axi-cel therapy, were also associated with shorter progression-free survival.

“是迫切需要与使用CAR T细胞疗法相关的毒性的新型治疗糖皮质激素节约战略”说Paolo Strati, M.D., lead author of the study and assistant professor of Lymphoma and Myeloma. “Next, we hope to conduct additional evaluation to understand the mechanisms underlying the association between corticosteroid therapy and early disease progression. Additionally, we will soon open a clinical trial investigating the safety and efficacy of anakinra, an IL-1 receptor antagonist, to mitigate CAR T cell therapy-associated toxicities; pre-clinical and retrospective clinical data supporting its use are promising, and we are excited to see how the study will unfold.”

See the abstract and co-authors here。