Dr Svoboda on the Investigation of huCART19-IL18 in Relapsed/Refractory Lymphoma

Jakub Svoboda, MD, associate professor, medicine, Hematology-Oncology, attending, the Hospital of the University of Pennsylvania; co-chair, Lymphoma Tumor Board and Case Conference; member, Data Safety Monitoring Committee, Abramson Cancer Center, discusses the ongoing investigation of armored huCART19-IL18 in patients with relapsed/refractory lymphomas following progression on treatment with an anti-CD19 CAR T-cell therapy.

, Svoboda and colleagues shared that treatment with huCART19-IL18 is associated with an acceptable safety profile and elicits durable remission rates in heavily pretreated patients who have relapsed/refractory lymphoma following prior CAR T-cell therapy.

In the field of lymphoma, there are several areas needing improvement, with a significant unmet need among patients who progress after receiving currently available anti-CD19 CAR T-cell therapies, Svoboda begins. These patients, particularly those who are relapsed/refractory following such treatments, were the focus of the clinical trial presentation at ASCO, he states. The innovative aspect of this product, referred to as an armored CAR T-cell therapy or fourth-generation CAR T-cell therapy, lies in its enhancements over existing therapies, Svoboda reports. This product is an autologous T-cell therapy similar to those currently on the market, but it includes modifications aimed at improving efficacy, he adds.

One key modification is that huCART19-IL18 can secrete interleukin (IL)–18, a pro-inflammatory cytokine, Svoboda expands. Preclinical studies indicate that IL-18 boosts the cytotoxic potential of T cells and may also alter the tumor microenvironment (TME), he says. Additionally, IL-18 exhibits anti-lymphoma properties. These enhancements, combined with the specificity of the CAR targeting CD19, provide significant advantages, Svoboda elucidates. By enhancing the cytolytic capabilities of T cells and potentially improving the TME, IL-18 contributes to the product’s overall efficacy against lymphoma, he notes. This phase 1, first-in-human clinical trial (NCT04684563) explored huCART19-IL18 to address unmet needs for patients relapsing after anti-CD19 CAR T-cell therapies, Svoboda concludes.

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Jakub Svoboda, MD, discusses the investigation of huCART19-IL18 in patients with relapsed/refractory lymphomas that have progressed.

Dr Svoboda on the Efficacy of Armored huCART19-IL18 in R/R Lymphoma

Jakub Svoboda, MD, associate professor, medicine, Hematology-Oncology, attending, the Hospital of the University of Pennsylvania; co-chair, Lymphoma Tumor Board and Case Conference; member, Data Safety Monitoring Committee, Abramson Cancer Center, discusses the observed safety and efficacy of armored huCART19-IL18 in patients with relapsed/refractory lymphomas that have progressed following treatment with an anti-CD19 CAR T cell therapy.

, Svoboda and his co-investigators presented findings on the safety and efficacy of armored huCART19-IL18 in this patient population. Key findings indicated that treatment with these armored CAR T cells is feasible and associated with an acceptable safety profile. Impressively, 81% (90% CI, 62%-93%) of patients achieved aresponse, with 52% (90% CI, 33%-71%) achieving complete responses, including patients who were refractory to currently available second-generation CAR T-cell therapies.

The trial’s results showed durable remissions lasting over 2 years in some patients, highlighting the potential effectiveness of targeting CD19 in lymphoma after prior CAR T-cell therapy. Researchers also noted that the efficacy did not significantly vary with different dose levels.

This type of first-in-human trial primarily focuses on safety, but one of the secondary objectives of this study was to evaluate the preliminary efficacy of armored huCART19-IL18 in patients with relapsed/refractory lymphomas, Svoboda begins, noting that investigators were encouraged by the performance of these armored CAR T cells in patients who were relapsed/refractory to prior second-generation CAR T-cell therapies. Although these are early data and should be interpreted with caution, Svoboda reports that durable responses were observed. The trial was initiated over 2 years ago, and some of the initially treated patients, who were clearly refractory to the second-generation CAR T cell therapies, remain in remission, he adds. It has been remarkable to see that a single infusion of CAR T cells in these patients, whose additional treatment options are limited, can result in such long-lasting remissions, Svoboda concludes.

Jakub Svoboda, MD, discusses outcomes with armored huCART19-IL18 in patients with previously treated relapsed/refractory lymphomas that have progressed.

Jakub Svoboda, MD, associate professor of Medicine, the Hospital of the University of Pennsylvania, physician, Penn Medicine, discusses the implications of the phase 3 SWOG 1826 trial (NCT03907488) of nivolumab (Opdivo) plus doxorubicin, vinblastine, and dacarbazine (AVD) in patients with advanced classical Hodgkin lymphoma.

Data presented from several studies during the 2023 ASCO Annual Meeting have the potential to make a significant impact on the lymphoma treatment landscape, including SWOG 1826, Svoboda begins. Previous data presented at the 2022 ASCO Annual Meeting from the phase 3 ECHELON-1 study (NCT01712490) of brentuximab vedotin (Adcetris) plus AVD in patients with stage III or IV classical Hodgkin lymphoma reconfirmed the role of this regimen as the standard of care in adult patients with advanced Hodgkin lymphoma, Svoboda explains.

However, findings from SWOG 1826 study presented in 2023 showed that the addition of nivolumab to AVD elicited a benefit over the standard brentuximab vedotin–based regimen, Svoboda expands. Data from SWOG 1826 showed that at a median follow-up of 12.1 months, nivolumab plus AVD produced a 1-year estimated progression-free survival (PFS) rate of 94% (95% CI, 91%-96%) compared with 86% (95% CI, 82%-90%) for brentuximab vedotin plus AVD (HR, 0.48; 99% CI, 0.27-0.87; 1-sided log-rank 

 = .0005). The nivolumab regimen has the potential to become the new standard of care with longer follow-up, Svoboda notes.

In addition to the PFS benefit, the toxicity profile of nivolumab plus AVD appeared to be more favorable in the nivolumab-containing regimen, Svoboda explains. The findings from the SWOG 1826 study could have a significant impact on the future of care for this patient population, Svoboda concludes.

Jakub Svoboda, MD, discusses the implications of the phase 3 SWOG 1826 trial of nivolumab plus doxorubicin, vinblastine, and dacarbazine in patients with advanced classical Hodgkin lymphoma.


Jakub Svoboda, MD

Articles

Dr Svoboda on the Investigation of huCART19-IL18 in Relapsed/Refractory Lymphoma

Dr Svoboda on the Efficacy of Armored huCART19-IL18 in R/R Lymphoma

Dr Svoboda on the Implications of Nivolumab Plus AVD in Classical Hodgkin Lymphoma