Tisagenlecleucel Shows Promise in Relapsed/Refractory Aggressive B-Cell NHL and Comorbidities in Real-World Setting

Daniel J. Landsburg, MD

Tisagenlecleucel (Kymriah) elicited durable efficacy and a favorable long-term safety profile in the real-world setting of patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma (NHL), according to data from a subgroup analysis from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry presented at the 2022 ASH Annual Meeting.¹

At a median follow-up of 23.2 months (range, 3.1-46.4), in the efficacy set (n = 968), the overall response rate (ORR) with commercial tisagenlecleucel was 59.5% (95% CI, 56.3%-62.6%) and the best overall response of complete response (CR) rate was 44.5% (95% CI, 41.4%-47.1%). The estimated progression-free survival (PFS) rate at 2 years was 28.4% (95% CI, 24.7%-32.1%), the 2-year duration of response (DOR) rate was 52.6% (95% CI. 46.9%-58.0%) and the estimated 2-year overall survival (OS) was 43.6% (95% CI, 39.1%-48.0%).

In patients who achieved a CR, the estimated rate of PFS at months 6, 12, and 24 were 76.2% (95% CI, 71.7%-80.1%), 63.7% (95% CI, 58.3%-68.5%), and 54.7% (95% CI, 48.2%-60.8%), respectively. In the overall population, the estimated PFS rates were 43.2% (95% CI, 40.0%-46.5%), 34.1% (95% CI, 30.8%-37.4%), and 28.4% (95% CI, 24.7%-32.1%) at months 6, 12, and 24.

Also in this subgroup, the 6-month DOR rate was 73.5% (95% CI, 68.4-77.9), the 12-month DOR rate was 65.9% (95% CI, 60.3%-71.0%), and the 24-month DOR rate was 61.4% (95% CI, 54.7%-67.3%).

Overall, the DOR rates in all responders were 64.3% (95% CI, 59.6%-68.6%), 56.9% (95% CI, 51.9%-61.6%), and 52.6% (95% CI, 46.9%-58.0%) at months 6, 12, and 24, respectively.

Finally, in patients who achieved a CR had a 6-month OS rate was 94.2% (95% CI, 91.4%-96.1%), 85.9% (95% CI, 81.6%-89.2%), and 75.2% (95% CI, 68.8%-80.5%) at months 6, 12, and 24. In all responders, the OS rate was 72.2% (95% CI, 70.2%-76.0%), 59.7% (95% CI, 56.1%-63.0%), and 43.6% (95% CI, 39.1%-48.0%) at months 6, 12, and 24.

“Data from the largest real-world cohort of patients treated with commercial tisa-cel shows high efficacy, which is durable, with a median follow up of almost 2 years, and a favorable long term safety profile,” lead study author Daniel J. Landsburg, MD, of Penn Medicine, in Philadelphia, Pennsylvania, said during a presentation of the data. “This subgroup analysis suggests that tisa-cel can safely and effectively treat a broad population of patients with relapsed aggressive lymphomas, including those who would have been considered ineligible for the JULIET trial.”

Landsburg is vice chief of quality and safety, in the Division of Hematology/Oncology, medical director of Infusion Services, at the Hospital of the University of Pennsylvania, a physician leader in the Oncology Clinical Effectiveness Team, and an associate professor of clinical medicine.

Tisagenlecleucel is an autologous CD19-directed T-cell immunotherapy indicated for use in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in May 2018 based on data from the phase 2 JULIET trial (NCT02445248). However, the phase 2 trial did not include certain patients with comorbidities or progression on past anti-CD19 therapies.

The CIBMTR Registry is the largest registered dataset to have data and information on patients who were treated with commercial tisagenlecleucel, who were also ineligible for the JULIET trial, leading to the inception of this real-world evaluation of data.

This non-interventional, prospective, longitudinal study utilized the CIBMTR Registry to examine data from 1159 patients who were treated with tisagenlecleucel across the United States, Canada, and Israel from May 2018 through May 2022. A total 968 of those patients were included in the efficacy set and 990 patients were included in the safety set.

A total 57.6% of patients were aged 65 years or older and 44.1% of patients had comorbidities, including ones that were pulmonary (26.3%), renal (3.1%), cardiac (16.0%), or hepatic (10.4%). Moreover, patients either had an EGOC score of 0 or 1 (83.4%), 2 or higher (4.7%), or an unknown score (11.8%).

Most patients (92.4%) had active disease at infusion, and 61% of patients had 3 or more prior therapies. A total 43.8% had an elevated LDH prior to infusion. Regarding histology, patients either had de novo DLBCL (61.5%), DLBCL with transformation (19.8%), or high-grade B-cell lymphoma (14.6%).

“Of note, patients with medical comorbidities had similar odds ratios for response and hazard ratios for survival events, as compared to those without medical comorbidities. Additionally, patients who achieve morphologic CR prior to infusion had a higher odds ratio for response and a lower hazard ratio for disease progression, as compared to those with active disease at the time of infusion,” Landsburg explained.

However, patients with elevated LDH had a lower odds ratio for response, and a higher hazard ratio for progression, relapse, and death compared with those who had a normal LDH.

Regarding safety, 58.2% of patients experienced any grade of cytokine release syndrome (CRS); grade 3 or higher CRS occurred in 6.0%.

Any-grade and grade 3 or higher immune effector cell-associated neurotoxicity syndrome occurred in 22.5% and 7.4% of patients, respectively. Neutropenia was observed in 6.7% of patients and thrombocytopenia was observed in 13.3% of patients.

“The presence of morphologic CR and a normal LDH prior to infusion are associated with improved efficacy and safety outcomes, which may support the use of bridging therapy for select patients in order to reduce disease burden prior to the time of infusion,” Landsburg concluded.

Tisagenlecleucel is also approved for the treatment of patients with relapsed or refractory follicular lymphoma following 2 or more lines of systemic therapy.

Reference

1. DJ Landsburg, Frigault M, Heim M, et. al. Real-world outcomes for patients with relapsed or refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (aBNHL) treated with commercial tisagenlecleucel: subgroup analyses from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry. Blood. 2022;140(suppl 1):1584-1587. doi:10.11