Unlocking the Potential of CAR T-Cell Therapy with NT-I7: A Promising Approach for Relapsed/Refractory DLBCL

In a groundbreaking study, researchers have unveiled the promising potential of NT-I7 (efineptakin alfa), a long-acting interleukin 7 (IL-7) agent, in enhancing the efficacy of standard-of-care (SOC) CD19-directed CAR T-cell therapies for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). The interim results, presented at the 2024 ESMO Congress, shed light on the safety and efficacy of this innovative combination approach.

Revolutionizing DLBCL Treatment with the Power of CAR T-Cell Therapy and NT-I7

Unlocking the Potential of CAR T-Cell Therapy

CAR T-cell therapy has emerged as a groundbreaking treatment option for patients with relapsed/refractory DLBCL, offering the potential for durable remissions and improved outcomes. However, the success of these therapies can be limited by factors such as suboptimal T-cell expansion and persistence. The introduction of NT-I7, a long-acting IL-7 agent, aims to address these challenges and enhance the efficacy of CAR T-cell therapies.IL-7 is a critical cytokine that plays a crucial role in T-cell homeostasis, proliferation, and survival. By administering NT-I7 after the infusion of CAR T-cell therapy, researchers sought to leverage the potent effects of this cytokine to amplify the expansion and persistence of the engineered T cells, ultimately improving their anti-tumor activity.

Exploring the Safety and Efficacy of the NT-I7 and CAR T-Cell Therapy Combination

The ongoing, multicenter phase 1b study (NCT04855283) enrolled patients with relapsed/refractory DLBCL who were eligible for SOC CD19-directed CAR T-cell therapy. Following the administration of tisagenlecleucel, lisocabtagene maraleucel, or axicabtagene ciloleucel, patients received varying doses of NT-I7 on day 21 post-CAR T infusion.The interim results from the study, presented by lead author Armin Ghobadi, MD, of the Washington University School of Medicine, revealed promising findings. Among the 11 patients treated with CAR T-cell therapy followed by one of the first five dose levels of NT-I7, the objective response rate (ORR) was an impressive 81.1%, with a complete response rate of 63.6% and a partial response rate of 18.2%. Notably, the progressive disease rate was only 18.2%.Furthermore, the median progression-free survival was 92.0 days, and the median overall survival was 363 days, underscoring the potential of this combination approach to improve clinical outcomes for patients with relapsed/refractory DLBCL.

Enhancing CAR T-Cell Factors for Improved Efficacy

The study findings also highlighted the ability of NT-I7 to enhance key factors associated with the efficacy of CAR T-cell therapies. Notably, the administration of NT-I7 on day 21 following CAR T-cell infusion led to the re-expansion of the CAR T-cell population, indicating the cytokine's potential to boost T-cell persistence and proliferation.Additionally, the researchers observed that while the distribution of CD4 and CD8 CAR T cells remained unchanged, the stemness of the CAR T cells was increased after the administration of NT-I7. This enhancement of CAR T-cell stemness is particularly significant, as it suggests the potential for improved long-term anti-tumor activity and durable responses.

Favorable Safety Profile of the NT-I7 and CAR T-Cell Therapy Combination

The safety profile of the combination therapy was also noteworthy. Among the 11 patients treated with NT-I7 at the first five dose levels, only grade 1/2 treatment-emergent adverse effects (TEAEs) related to NT-I7 were reported, with no instances of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome observed.The most common TEAEs related to NT-I7 were injection site erythema and swelling, both of which were reported in 18.2% of patients. Importantly, no grade 3 or higher TEAEs related to NT-I7 were observed, suggesting a favorable tolerability profile for this combination approach.

Unlocking New Possibilities in DLBCL Treatment

The interim results from this phase 1b study highlight the promising potential of combining NT-I7 with standard-of-care CD19-directed CAR T-cell therapies for the treatment of relapsed/refractory DLBCL. By enhancing the expansion, persistence, and stemness of CAR T cells, NT-I7 has demonstrated the ability to improve the efficacy of these transformative therapies, offering hope for patients with this challenging disease.As the study progresses, further exploration of the optimal dosing and timing of NT-I7 administration will be crucial to fully unlock the potential of this combination approach. Additionally, the continued evaluation of long-term outcomes and the expansion of the patient population will provide valuable insights into the broader applicability of this innovative strategy.The findings from this study underscore the importance of ongoing research and collaboration in the field of DLBCL treatment, as the integration of novel agents like NT-I7 with established therapies holds the promise of enhancing patient outcomes and transforming the landscape of care for individuals battling this aggressive form of lymphoma.