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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)

Program: Oral and Poster Abstracts
Type: Oral
Session: 906. Outcomes Research: Lymphoid Malignancies Excluding Plasma Cell Disorders: CAR-T Cell Therapy in Action: Real-World Outcomes in Lymphoma
Hematology Disease Topics & Pathways:
Research, Adult, Lymphomas, Non-Hodgkin lymphoma, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Real-world evidence, Treatment Considerations, Biological therapies, Lymphoid Malignancies, Study Population, Human
Sunday, December 8, 2024: 10:15 AM

Dasom (Caroline) Lee, MD1*, Swetha Kambhampati Thiruvengadam, MD2, Maria Silvina Odstrcil Bobillo, MD3*, Babatunde Adedokun, MD, PhD4*, Mazyar Shadman, MD, MPH5*, Amanda L. Olson, MD6, Alex F. Herrera, MD7, Catherine J. Lee, MD, MSc8, Caron A. Jacobson, MD, MMSc9, Matthew Bye, MPH10*, Mehdi Hamadani, MD10, Soyoung Kim, PhD11*, Saurabh Dahiya, MD, FACP12*, Zhen-Huan Hu, MPH4*, Kelly Speth, PhD4*, Christina To, MD4*, Debbie L. Mirjah, MD13*, Timothy Best, PhD4*, Frederick L. Locke, MD14, Nausheen Ahmed, MD15*, Michael T. Tees, MD, MPH16, Marcelo C. Pasquini, MD, MS17 and Sairah Ahmed, MD18

1Division of Hematology, Stanford University, Palo Alto, CA
2City of Hope National Medical Center, Yorba Linda, CA
3University of Utah, Salt Lake City, UT
4Kite, a Gilead Company, Santa Monica, CA
5University of Washington, Fred Hutchinson Cancer Research Center and Medical Oncology Division, Seattle, WA
6The University of Texas MD Anderson Cancer Center, Houston, TX
7Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
8University of Washington, 5Fred Hutchinson Cancer Center and Medical Oncology Division, Seattle, WA
9Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
10Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI
11Center for International Blood and Marrow Transplant Registry (CIBMTR), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
12Division of Hematology, Stanford University, Stanford, CA
13Kite Pharma, a Gilead Company, Santa Monica, CA
14Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL
15Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS
16HCA Healthcare, Sarah Cannon Transplant and Cellular Therapy Network, Denver, CO
17Dana Farber Cancer Institute, Boston, MA
18Department of Lymphoma/Myeloma and Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX

Introduction

In the Phase 3 ZUMA‑7 study (NCT03391466), axi-cel, an autologous anti-CD19 CAR T-cell therapy, showed superior event-free survival (EFS; Locke FL, et al. NEJM 2022), response rate, and overall survival (OS) vs standard of care (Westin JR, et al. NEJM 2023) in transplant-intended R/R LBCL. Axi-cel is approved in many countries for R/R LBCL within 12 mo after first-line therapy. A Phase 2 trial (ALYCANTE; NCT04531046) additionally demonstrated high response and durable remissions in transplant-ineligible pts (Houot R, et al. Nat Med 2023). In the real world, pts receiving second-line (2L) axi-cel may have a broader range of pt and/or disease characteristics that would have precluded eligibility in these trials. This study evaluated early real-world effectiveness and safety outcomes of US pts who received axi-cel as a 2L treatment of R/R LBCL.

Methods

Adult pts with R/R LBCL who received commercial axi-cel in 2L between Apr 2022–July 2023 in the US and enrolled in the CIBMTR® data registry were included. Descriptive statistics summarized baseline pt characteristics and post-infusion outcomes in the overall population, by ZUMA-7 eligibility (adapted to data available in CIBMTR), and in pts with PMBCL. When sufficient data were available, 12-mo data were reported; otherwise, 6-mo data were reported.

Results

Across 89 centers, 446 pts received axi-cel (DLBCL, 78%; PMBCL, 3%; high grade B-cell lymphoma, 18%; follicular lymphoma grade IIIB, 1%). Median age at infusion was 63.9 y (range, 19.5–86.0; 47% ≥65 y); 64% of pts were male; 97% had ECOG 0 or 1; 72% were non-Hispanic White, 12% were Hispanic, 6% were non-Hispanic Asian, and 5% were non-Hispanic Black. Most had ≥1 clinically significant comorbidity (71%; Sorror ML, et al. Blood 2005). Prior to infusion, 48% had elevated lactate dehydrogenase and 25% had complete response (CR) as best response to last line of therapy prior to leukapheresis. Median vein-to-vein time was 29 days (IQR, 27–35). Most received bridging therapy (66%; systemic, 53%; radiation, 16%). Lymphodepleting chemotherapy regimens were mostly cyclophosphamide plus fludarabine (75%) or bendamustine (22%). Half (52%) would have been ineligible for ZUMA-7, mainly due to organ impairment (34%) and prior malignancy (16%).

Among all pts, at a median follow-up of 12.0 mo, objective response rate (ORR) was 79% (95% CI, 75–82), with a CR rate of 64% (95% CI, 60–69). The 12-mo rate (95% CI) of duration of response (DOR) was 66% (59–71), progression-free survival (PFS) was 53% (48–58), EFS was 53% (48–58), and OS was 71% (66–76). Any-grade cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) were reported in 87% (Grade [Gr] ≥3, 5%) and 50% (Gr ≥3, 22%), respectively. To treat pts with any CRS and/or ICANS (n=398, 89%), tocilizumab, corticosteroids, and anakinra were given to 80%, 65%, and 18%, respectively. Median duration of CRS and ICANS was 5 days (IQR, 4–7) and 6 days (IQR, 3–10), respectively. Prolonged cytopenias (by Day 30; n=440) were reported in 16% of pts (neutropenia, 7%; thrombocytopenia, 11%); infections were reported in 44%. Cumulative incidence of non-relapse mortality at 6 mo was 4%.

When assessed by ZUMA-7 eligibility, ORRs (95% CI) in ineligible pts (n=219; excluding pts with PMBCL) and eligible or unknown pts (n=214) were 79% (72–84) and 79% (73–85), respectively, with CR rates of 63% (56–69) and 65% (58–72). The 12-mo rates (95% CI) of DOR in ZUMA-7 ineligible and eligible or unknown pts were 60% (50–68) and 69% (60–77), PFS was 48% (40–55) and 58% (51–65), EFS was 48% (40–55) and 58% (50–64), and OS was 62% (53–69) and 80% (73–85), respectively. Incidence of any-grade CRS was 88% in ZUMA-7 ineligible pts and 87% in ZUMA-7 eligible or unknown pts.

Among 13 pts with PMBCL, ORR was 69% (95% CI, 39–91); all with CR. The 6-mo rates (95% CI) of DOR, PFS, EFS, and OS were 100%, 68% (36–87), 68% (36–87), and 100%, respectively. Incidence of any-grade CRS and ICANS was 85% (Gr ≥3, 0%) and 54% (Gr ≥3, 9%), respectively. Prolonged cytopenias were reported in 8% of pts. Incidence of infections was 38%.

Conclusions

This is the largest real-world analysis of pts with R/R LBCL who received 2L commercial axi-cel. Despite a broader pt population beyond the ZUMA-7 and ALYCANTE trials, outcomes at median follow-up of 12 mo were consistent with those observed in ZUMA-7.

DCL, SK, and MSOB contributed equally.

Disclosures: Thiruvengadam: ADC-Therapeutics: Research Funding; Ipsen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genmab: Consultancy, Research Funding; Abbvie: Consultancy; Genentech: Research Funding. Adedokun: Amgen: Current Employment, Current equity holder in publicly-traded company, Other: Travel support; Kite, a Gilead Company: Current Employment, Current equity holder in publicly-traded company, Other: Travel support. Shadman: BeiGene: Consultancy, Research Funding; Fate Therapeutics: Consultancy; Mustang Bio, Genentech, AbbVie/Pharmacyclics, Beigene, AstraZeneca, Genmab, Morphosys/Incyte, Vincerx, BMS, TG Therapeutics: Research Funding; Koi Biotherapeutics: Current holder of stock options in a privately-held company; AbbVie/Pharmacyclics, Genentech, AstraZeneca, Genmab, Janssen, Beigene, Bristol Myers Squibb, Morphosys/Incyte, Kite Pharma, Eli Lilly, Fate Therapeutics, Nurix, Merck, ADC Therapeutics, MEI Pharma, MustangBio, Regeneron: Consultancy; BMS: Other: Current employment of spouse; AstraZeneca: Consultancy, Research Funding; Adaptimmune: Consultancy; Abbvie: Consultancy, Research Funding; Atara Biotherapeutic: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Lilly: Consultancy; Epizyme: Consultancy; Genentech: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy; Innate Pharma: Consultancy; Kite, a Gilead Company: Consultancy; MEI Pharma: Consultancy; Merck: Consultancy; MorphoSys/Incyte: Consultancy, Research Funding; Mustang Bio: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Regeneron: Consultancy; Sound Biologics: Consultancy; TG Therapeutics: Consultancy, Research Funding; Celgene: Research Funding; Genmab: Research Funding; Gilead Sciences: Research Funding; Sunesis: Research Funding. Herrera: AbbVie: Consultancy; Genmab: Consultancy; Roche/Genentech: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Karyopharm: Consultancy; Seattle Genetics: Consultancy, Research Funding; KiTE Pharma: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Regeneron: Consultancy; Takeda: Consultancy; Adicet Bio: Consultancy; Caribou Biosciences: Consultancy; Allogene Therapeutics: Consultancy; AstraZeneca: Consultancy, Research Funding; Gilead Sciences: Research Funding; Pfizer: Consultancy; Merck: Consultancy, Research Funding; Tubulis: Consultancy. Lee: ScientiaCME: Consultancy; Aptitude Health: Consultancy; Incyte: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Speakers Bureau; SEI: Consultancy. Jacobson: Miltenyi: Consultancy; Instil Bio: Consultancy; ImmPACT Bio: Consultancy; Daiichi Sankyo: Consultancy; MorphoSys: Consultancy; Bristol Myers Squibb/Celgene: Consultancy; Ipsen: Consultancy; Pfizer: Research Funding; ADC Therapeutics: Consultancy; Caribou Biosciences: Consultancy; Synthekine: Consultancy; Novartis: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Abintus Bio: Consultancy; AbbVie: Consultancy. Hamadani: Genmab: Consultancy; Forte Biosciences: Consultancy; AbbVie: Consultancy; Sanofi Genzyme: Speakers Bureau; Caribou: Consultancy; CRISPR: Speakers Bureau; AstraZeneca: Speakers Bureau; BeiGene: Speakers Bureau; Byondis: Consultancy; Myeloid Therapeutics: Speakers Bureau; ADC Therapeutics: Consultancy, Research Funding, Speakers Bureau; Spectrum Pharmaceuticals: Research Funding; Kite Pharma: Consultancy, Speakers Bureau; Astellas Pharma: Research Funding; Genentech: Speakers Bureau; CRISPR: Consultancy; DMC, Inc: Speakers Bureau; Allovir: Consultancy; Autolus: Consultancy; Omeros: Consultancy; BMS: Consultancy; Takeda: Research Funding. Dahiya: Bristol Myers Squibb: Consultancy; Kite-Pharma-Gilead: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy. Hu: Kite, a Gilead Company: Current Employment; Gilead Sciences: Current equity holder in publicly-traded company. Speth: Kite, a Gilead Company: Current Employment, Research Funding; Gilead Sciences: Current equity holder in publicly-traded company. To: Kite, a Gilead Company: Current Employment; Gilead Sciences: Current equity holder in publicly-traded company. Mirjah: Kite, a Gilead company: Current Employment; Gilead Sciences: Current equity holder in publicly-traded company. Best: Kite, a Gilead Company: Current Employment; BMS: Ended employment in the past 24 months; Gilead Sciences: Current equity holder in publicly-traded company. Locke: Legend Biotech: Consultancy; Novartis: Consultancy, Research Funding; Calibr: Consultancy; Pfizer: Consultancy; Wugen: Consultancy; Aptitude Health: Honoraria; BioPharma: Honoraria; Moffit Cancer Center: Patents & Royalties: cellular immunotherapy; Gerson Lehrman Group (GLG): Consultancy; Caribou: Consultancy; A2: Consultancy; Society for Immunotherapy of Cancer: Honoraria; iMedX: Honoraria; Clinical Care Options Oncology: Honoraria; Communications CARE Education: Honoraria; Gilead Company: Consultancy; Kite, a Gilead Company: Consultancy, Other: Travel support, Research Funding; Janssen: Consultancy; Iovance: Consultancy; GammaDelta Therapeutics: Consultancy; Emerging Therapy Solutions Gerson Lehman Group: Consultancy; ecoR1: Consultancy; 2SeventyBio: Research Funding; Umoja: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Allogene: Consultancy, Research Funding; BMS: Consultancy, Research Funding; ASH: Honoraria, Other: Travel support; Bluebird Bio: Consultancy, Research Funding; Aptitude Health: Honoraria; CERo Therapeutics: Research Funding; Sana: Consultancy; Cowen: Consultancy; Cellular Biomedicine Group: Consultancy; National Cancer Institute: Research Funding; Leukemia and Lymphoma Society Scholar in Clinical Research: Research Funding. Ahmed: Kite, a Gilead Company: Research Funding; Bristol Myers Squibb: Consultancy. Tees: Juno: Research Funding; Allogene: Research Funding; Merck&Co./Arqule: Research Funding; NKarta: Research Funding; Kite: Research Funding; Syneos: Research Funding; Nurix: Research Funding; 2seventy: Research Funding; STEP: Research Funding; Accutar: Research Funding; Cargo: Research Funding. Pasquini: Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Research Funding; Janssen: Research Funding; Kite, a Gilead Company: Honoraria, Research Funding. Ahmed: Merck: Research Funding; Janssen: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Nektar: Research Funding; Bristol Myers Squibb: Research Funding; Myeloid Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Xencor: Research Funding.

*signifies non-member of ASH