Yescarta Shows Curative Potential in Lymphoma

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Abstract #526 Real-World Early Outcomes of Second-Line Axicabtagene Ciloleucel (Axi-Cel) Therapy in Patients (Pts) With Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL) The largest real-world analysis of 446 patients from 89 U.S. centers from the CIBMTR Registry with LBCL (diffuse LBCL [DLBCL], 78%; primary mediastinal LBCL [PMBCL], 3%; high-grade B-cell lymphoma, 18%; follicular lymphoma grade IIIB, 1%) who received second-line Yescarta treatment demonstrated outcomes consistent with the ZUMA-7 study across broader patient and disease characteristics than those included in the ZUMA-7 pivotal study or Phase II ALYCANTE study, at a median of 12-months of follow-up.

Among all patients, ORR was 79% (95% confidence interval [CI], 75–82), with a CR rate of 64% (95% CI, 60–69). The 12-month rate of duration of response (DOR) was 66% (95% CI, 59–71), progression-free survival (PFS) was 53% (48–58), event-free survival (EFS) was 53% (48–58), and OS was 71% (66–76). Any-grade CRS and ICANS were reported in 87% (Grade ≥ 3, 5%) and 50% (Grade ≥ 3, 22%), respectively.

When assessed by ZUMA-7 eligibility, ORRs in ineligible patients (n=219) versus eligible or unknown patients (n=214) were both 79%, respectively, with CR rates of 63% and 65%, respectively. At 12-months, DOR in ZUMA-7 ineligible and eligible or unknown patients were 60% and 69%, PFS were 48% and 58%, EFS were 48% and 58%, and OS were 62% and 80%, respectively. Incidence of ICANS was 54% in ZUMA-7 ineligible patients and 45% in ZUMA-7 eligible or unknown patients. Among 13 patients with PMBCL, ORR was 69% (95% CI, 39–91), all with CR. The six-month rate (95% CI) of DOR was 100%, PFS was 68%, EFS was 68%, and OS was 100%. Incidence of any-grade CRS was 85% and ICANS was 54%.

Abstract #527 Real-world Trends of Cytokine Release Syndrome and Neurologic Events, and Pattern of Their Management among Patients Receiving Axicabtagene Ciloleucel for Relapsed or Refractory (r/r) Large B-cell Lymphoma (LBCL) in the U.S.: a CIBMTR Report  Real-world data from 1,615 patients with R/R LBCL from 109 U.S. centers from the CIBMTR registry demonstrated a decreasing trend in incidence, severity and duration of CRS and ICANS following treatment with Yescarta for adult patients with R/R LBCL in the third-line-plus setting. Patients who received Yescarta during 2022–2023 (n=206) and 2020–2021 (n=486) had significantly lower incidences of Grade ≥ 3 CRS compared to those treated during 2017–2019 (n=923, odds ratio [OR] 0.17, 95% CI, 0.07−0.41, and OR 0.63, 95% CI, 0.43−0.94, respectively). Furthermore, patients treated in the later time periods of 2022-2023 and 2020-2021 experienced significantly shorter duration of CRS compared to 2017-2019 (hazard ratio [HR] 1.36, 95% CI, 1.14-1.64, and HR 1.34, 95% CI, 1.18-1.52, respectively).

Patients who received Yescarta during 2022–2023 and 2020–2021 had a significantly lower incidence of any-grade ICANS compared to those treated in 2017–2019 (OR 0.47, 95% CI, 0.34−0.66, and OR 0.63, 95% CI, 0.50−0.80, respectively). The duration of ICANS was also significantly shorter for those treated in 2020-2021 compared to 2017-2019 (HR 1.21, 95% CI, 1.02-1.43)

The rates of use of tocilizumab and corticosteroids for the treatment of CRS/ICANS were consistent for the three periods, although there was an increasing trend of anakinra use (1%, 6%, and 13%, respectively). Concerning other adverse events, rates of prolonged thrombocytopenia and clinically significant infections were consistent.

Abstract #4505 Health-related quality of life after Axi-cel as a second-line therapy in patients with high-risk relapsed/refractory large B-cell lymphoma who are ineligible for autologous stem cell transplantation: results of the ALYCANTE phase II trial  New HRQoL findings from the Phase II ALYCANTE study, led and sponsored by the French collaborative group LYSA/LYSARC, for use of Yescarta in patients with R/R LBCL after one prior line of therapy who were deemed ineligible for high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT), demonstrated that after a short initial deterioration at one-month post-infusion, patients reported longer-term stable or improved quality of life across parameters, after up to 12 months of follow-up.

Findings from 61 patients included in the ALYCANTE study reported a lower symptomatic level, noted by lower HRQoL, at three months compared to baseline, with a clinically significant difference for pain (mean=11.9 [95% CI, 5.4-18.4] at three months vs. 25.1 [95% CI, 17.7-32.6] at baseline), emotional impact (mean=12.9 [95% CI, 8.6-17.2] vs. 23.8 [95% CI, 17.9-29.6]) and worries/fears about health and functioning (mean=22.1 [95% CI, 16.8-27.3] vs. 33.0 [95% CI, 27.2-38.8]).

At three months post Yescarta infusion, 45% of patients presented a stable global health condition and 73% stable physical functioning. In the longer-term, at 12 months post-infusion, patients reported stable states, with clinically and statistically significant improvement in 4/22 HRQoL measures. Analyses confirmed findings observed over time for global health status, physical functioning and visual analogue scale (VAS, common valuation method to provide a single-index measure of HRQoL) were consistent between both the ALYCANTE and pivotal ZUMA-7 study.

“It is reassuring that the largest real-world dataset for axi-cel as a second-line treatment for relapsed/refractory large B-cell lymphoma, across a broader patient population than the ZUMA-7 pivotal study or Phase II ALYCANTE study for transplant-ineligible patients, has demonstrated consistent outcomes at 12-months median follow-up as in ZUMA-7,” said Dr. Dasom (Caroline) Lee, Lead Investigator on the study and Fellow, Hematology and Medical Oncology, Stanford Medicine. “These data should provide further confidence to physicians that earlier use of axi-cel can provide the best chance for overall survival and possibly a cure for these patients.”

“Over the past seven years, there has been wider adoption of CAR T-cell therapies as a standard treatment for patients, and the knowledge, skills, and experience needed to administer the therapies safely and effectively has grown,” said Dr. Jiasheng Wang, Assistant Professor of Medicine, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. “This real-world analysis reflects a growing understanding in clinical tools such as prophylactic and preemptive management strategies that can help manage axi-cel patients safely and effectively.”

"ALYCANTE is the first study to assess axi-cel as second-line therapy in transplant-ineligible relapsed/refractory large B-cell lymphoma patients, with previous study findings confirming its efficacy in this patient population,” said Prof. Roch Houot, Head of Haematology Department, University Hospital of Rennes, France and coordinator of the ALYCANTE study. “This current study shows that, in this frail and elderly population, axi-cel not only increased the quantity of life but also improved the quality of life which was comparable to that of the transplant-eligible patients, and allowed recovery of a fatigue score close to the general French population.”