{"id":139030,"date":"2025-10-22T20:29:34","date_gmt":"2025-10-22T20:29:34","guid":{"rendered":"https:\/\/www.europesays.com\/ie\/139030\/"},"modified":"2025-10-22T20:29:34","modified_gmt":"2025-10-22T20:29:34","slug":"real-world-studies-reinforce-axi-cel-and-liso-cel-as-effective-lbcl-treatments","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/ie\/139030\/","title":{"rendered":"Real-World Studies Reinforce Axi-Cel and Liso-Cel as Effective LBCL Treatments"},"content":{"rendered":"

How have the FDA approvals of axi-cel and liso-cel affected the LBCL treatment paradigm?<\/strong><\/p>\n

Five years ago, irrespective of relapse status or primary refractoriness, the standard of care would have been salvage platinum-containing chemotherapy followed by high-dose therapy and hematopoietic progenitor cell transplant. Nowadays, [based on] head-to-head [data], we have a superior therapy to offer these patients. Axi-cel has been demonstrated to have a benefit in both event-free and overall survival [OS]. Liso-cel confers an early benefit in event-free survival, with OS data still yet to mature as more follow-up is accrued.<\/p>\n

Now, the treatment algorithm\u00a0and what product and approach might be the most beneficial for each patient in any setting\u00a0[is based on] refractory status, the timing of relapse, and whether a patient is eligible for autologous stem cell transplant, CAR T-cell therapy, or potentially both. Although [CAR T-cell therapy is] a new treatment modality, it has complicated the treatment paradigm and makes decision-making much more difficult, nuanced, and profound when taking into account patients’ overall health, as well as their wishes and desires about how they want to be treated.<\/p>\n

What were the findings from the real-world CIBMTR study of axi-cel in patients with relapsed\/refractory LBCL?<\/strong><\/p>\n

Studies show that [axi-cel and liso-cel] are effective in trial settings, but real-world data are starting to emerge that support the use of this strategy in practice. The first of the [CAR T-cell therapy] studies to emerge in the real world was from investigators leading a CIBMTR analysis through Stanford University.1 In this CIBMTR analysis, adult patients similar to [those in] the phase 3 ZUMA-7 trial [NCT03391466] population with relapsed\/refractory LBCL who received commercial axi-cel in the second-line setting between April 2022, and July 2023, in the United States were included.<\/p>\n

[Approximately] 446 patients at [approximately] 90 centers received axi-cel. The median age was [about] 64 years, most patients were male, and most patients had diffuse LBCL [DLBCL] not otherwise specified [NOS]. [Approximately] three-quarters of these patients were refractory to frontline therapy, and most patients required some form of holding or bridging therapy. Interestingly [investigators evaluated] whether these CIBMTR-included patients would have been eligible for the registrational trial, and [about] 52% of these patients would have been deemed ineligible for ZUMA-7 with [around] one-third of patients being ineligible due to some form of organ impairment. This suggests that that this strategy of axi-cel in the second-line setting can be feasible, and the results [can be] extrapolated to people who might not have been enrolled on the [pivotal] study due to performance status or organ dysfunction. <\/p>\n

In the real world, at a short median follow-up of 12 months, the overall response rate [with axi-cel] was similar to [that seen in] the trial, at [approximately] 79%, with a complete response rate of [around] 64%. At [about] 12 months, the median duration of response was [approximately] 66%. The progression-free and event-free survival rates were both [near] 53%, and the OS rate was [about] 71% at 1 year. These outcomes were not different among patients who would have been eligible or not eligible for ZUMA-7, according to a subgroup analysis that these investigators performed.<\/p>\n

Any-grade cytokine release syndrome [CRS] and neurotoxicity were reported in [about] 87% and 50% of patients, respectively, in this study. Almost all patients received treatment for these complications, including tocilizumab [Actemra], steroids, and anakinra [Kineret], similar to what was observed in the [clinical trials]. The median duration of CRS and neurotoxicity were [approximately] 5 and 6 days, respectively. Interestingly, prolonged cytopenia at 30 days or more post-CAR T-cell therapy was reported in [approximately] 16% of patients, highlighting an emerging and increasingly well-recognized toxicity [associated with] these therapies. Fortunately, even in a group of patients where many would have been excluded from registrational studies and had comorbidities, the cumulative incidence of non-relapse mortality [NRM] at 6 months in this study was low, at only [around] 4%.<\/p>\n

What real-world data have been shown with liso-cel in relapsed\/refractory LBCL?<\/strong><\/p>\n

A real-world analysis of the use of liso-cel in the second-line setting<\/strong><\/a> in high-risk patients has also been carried out another CIBMTR-based effort led by investigators at the University of Utah.2 [This study] described the real-world outcomes of liso-cel use in this population and included patients treated in the second-line between June 2022 and [August] 2024. The median age was a little older compared with the axi-cel patients, at 72 years [range, 27-85], with [approximately] half of the patients in this CIBMTR study being over the age of 70 years. [A total of 8% of] patients had DLBCL NOS, [50%] of patients were primary refractory, and 67% of patients would have been ineligible for the phase 3 TRANSFORM study [NCT03575351] at a short follow-up of [approximately\u2019 6 months; this was necessarily short because of the shorter time [from the] approval [of liso-cel to the time of the real-world analysis].<\/p>\n

The overall and complete response rates were 84% [95% CI, 77%-89%] and 70% [95% CI, 62%-77%] respectively. Median survival outcomes had not yet been reached. CRS and neurotoxicity were common, though lower compared with real-world data on the use of axi-cel. CRS occurred at any grade at a rate of 45%, and immune effector cell\u2013associated neurotoxicity syndrome [(ICANS) occurred at a rate] of 20%. In this real-world population, there were no grade 4 or 5 ICANS events, and there was only 1 death attributable to CRS. Similarly, long-term cytopenias [arising] at least 30 days after the receipt of liso-cel occurred in [11%] of patients, and [33%] of patients had clinically significant infections, though the 6-month cumulative incidence of NRM was only [1.3% (95% CI, 0.3%-4.3%)].<\/p>\n

References<\/strong><\/p>\n

    \n
  1. Lee D, Kambhampati S, Bobillo MSO, et al. 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). Blood. 2024;144(suppl 1):526. doi:10.1182\/blood-2024-199139<\/li>\n
  2. Bobillo MSO, Thiruvengadam SK, et al. Lee D, et al. Real-world (rw) outcomes of lisocabtagene maraleucel (liso-cel) as second-line (2L) therapy in patients (pts) with relapsed or refractory (r\/r) large B-cell lymphoma (lbcl): first results from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry. Blood. 2024;144(suppl 1):470. doi:10.1182\/blood-2024.199723<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"How have the FDA approvals of axi-cel and liso-cel affected the LBCL treatment paradigm? Five years ago, irrespective…\n","protected":false},"author":2,"featured_media":139031,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[78],"tags":[18,135,19,17],"class_list":{"0":"post-139030","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-health","8":"tag-eire","9":"tag-health","10":"tag-ie","11":"tag-ireland"},"share_on_mastodon":{"url":"","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/139030","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/comments?post=139030"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/139030\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media\/139031"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media?parent=139030"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/categories?post=139030"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/tags?post=139030"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}