Actual-world therapy with the autologous anti-CD19 CAR T-cell remedy Yescarta (axicabtagene ciloleucel; axi-cel) demonstrated sturdy responses and a manageable security profile amongst sufferers with relapsed/refractory follicular lymphoma, based on findings from a big observational evaluation which have been introduced in a poster presentation on the 2025 ASH Annual Assembly.
Amongst 238 sufferers at a median follow-up of 24.1 months, researchers reported an goal response charge (ORR) of 96% (229 sufferers), together with a whole response (CR) in 91% of sufferers (216 sufferers) and partial responses in 5% (13 sufferers).
At two years, the period of response (DOR) was 70%, and the period of full response (DOCR) was 66%. Two-year progression-free survival (PFS) was 64% and two-year total survival (OS) was 84%.
Glossary
Goal Response Charge (ORR): The proportion of sufferers whose tumors shrink or disappear after therapy.
Full Response (CR): When all indicators of most cancers disappear after therapy. This doesn’t at all times imply the most cancers is cured, however no most cancers may be detected.
Partial Response (PR): When most cancers shrinks however doesn’t utterly go away. It nonetheless counts as a optimistic impact of therapy.
Development-Free Survival (PFS): The period of time throughout and after therapy {that a} affected person lives with out the most cancers getting worse.
General Survival (OS): The size of time from the beginning of therapy (or analysis) that sufferers are nonetheless alive, no matter whether or not the most cancers has grown.
Cytokine Launch Syndrome (CRS): A potential aspect impact of sure immunotherapies (equivalent to CAR-T remedy). It occurs when immune cells change into extremely activated and launch chemical substances referred to as cytokines, inflicting flu-like signs equivalent to fever, fatigue or low blood strain.
Immune Effector Cell-Related Neurotoxicity Syndrome (ICANS): One other potential aspect impact of therapies like CAR-T remedy. ICANS impacts the mind and nervous system and might trigger confusion, complications, problem talking, or adjustments in conduct. Most instances are momentary and treatable.
Furthermore, researchers reported that univariate and multivariable evaluation demonstrated that prior bendamustine publicity was related to decreased CR charges, in addition to shorter DOR and PFS. Moreover, the presence of average or extreme pulmonary comorbidity was related to shorter OS.
“In our real-world expertise, [Yescarta] in relapsed or refractory follicular lymphoma confirmed sturdy responses and a manageable security profile just like that seen in ZUMA-5,” stated Dr. Aung Tun, of The College of Kansas Well being System, in a poster summary session presentation of the information.
These information confirmed outcomes broadly in keeping with these noticed within the part 2 ZUMA-5 trial, which supported the
Tun continued: “The usage of bendamustine as a lymphodepleting remedy was related to a decreased efficacy; nonetheless that pattern dimension was fairly small, solely 14 [patients], and it’s tough to attract conclusions. The prior use of bendamustine for lymphoma remedy was related to fewer sturdy responses; nonetheless, that information on the timing of bendamustine publicity was not obtainable. It’s tough to know whether or not the inferior end result was due to the latest bendamustine remedy.”
Examine Background and Affected person Traits
Though the regulatory company accredited Yescarta therapy for this affected person inhabitants in 2021, the examine investigators clarify of their poster that long-term assessments of security and effectiveness are necessary as a result of real-world sufferers have broader demographics, illness traits and comorbidities than those that enroll in scientific trials.
Information for this observational, real-world evaluation was collected from the Heart for Worldwide Blood and Marrow Transplant Analysis (CIBMTR) registry, together with consenting adults within the U.S. with relapsed or refractory follicular lymphoma who obtained industrial Yescarta between March 2021 and October 2023.
Investigators aimed to be taught extra in regards to the ORR and CR charges of sufferers, in addition to the DOR, PFS, and OS outcomes. Cytokine launch syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), together with extended cytopenias, clinically vital infections, subsequent neoplasms and nonrelapse mortality, have been additionally outcomes of curiosity to the examine investigators.
Sufferers’ median age at infusion was 61 years, with 38% of sufferers aged at the least 65 years outdated; 58% of sufferers have been male. Concerning Karnofsky efficiency rating (KPS), most sufferers (54%) had a rating from 90 to 100, 35% had a KPS of 80 and 11% had a KPS of 70 or much less.
Clinically vital comorbidities have been current in 75% of sufferers, and included cardiac (15%), hepatic (6%) and average to extreme pulmonary comorbidities (18%). Over half of sufferers (67%) have been recognized with stage 3 or 4 illness. Moreover, sufferers had obtained a median of 4 prior traces of remedy, together with prior autologous hematopoietic cell transplantation (14%), bendamustine (74%) and bridging remedy (32%).
Security of Yescarta
Grade 1/2 CRS was noticed in 74% of sufferers (176 sufferers), with grade 3 (extreme) or increased CRS occurring in 4% (10 sufferers). ICANS was reported at a grade 1 (delicate)/2 (average) in 42% of sufferers (99 sufferers), whereas grade 3 or increased ICANS was reported in 18% (42 sufferers). Extended neutropenia and extended thrombocytopenia have been reported at any grade in 10% and eight% of sufferers, respectively.
In multivariable analyses of security outcomes, sufferers who have been reported to be 65 years or older had an elevated danger of any-grade ICANS (OR/HR, 2.31; 95% CI, 1.18-4.50). Prior publicity to bendamustine for was related to a decrease danger of any-grade CRS, in addition to a decrease danger of any-grade ICANS.
The median time from therapy infusion to onset of CRS and ICANS was 5 and eight days, respectively. The median period of each antagonistic results was 5 days.
Furthermore, investigators reported that the cumulative incidence of clinically vital infections at six months was 29% and the cumulative incidence of myelodysplastic syndrome and acute myeloid leukemia as subsequent neoplasms at 24 months was 4%.
General, 14% of sufferers died from follicular lymphoma (10 sufferers), organ failure (seven sufferers) and an infection (10 sufferers).
“[There were] no extra associations between key demographic or scientific variables with security [that] have been noticed,” the investigators wrote within the poster.
References
“Actual-world effectiveness and security outcomes by age, comorbidity, frailty, and coverings previous to infusion in relapsed or refractory (R/R) follicular lymphoma sufferers handled with axicabtagene ciloleucel,” Dr. Aung Tun et al., Blood.
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