S. Ahmed, J. L. Reguera Ortega, F. Morschhauser, G. Cartron, A. P. Rapoport, K. Izutsu, H. Ghesquieres, M. L. Palomba, H. Goto, J. Kuruvilla, J. S. Abramson, P. Borchmann, U. Jäger, M. Kamdar, M. Bar, M. Strocchia, M. Raggi, R. Nishii, A. M. García-Sancho
{"title":"Lisocabtagene maraleucel在r / r fl （transcend fl）中的作用：既往治疗线、苯达莫司汀暴露和≤24个月初始全身治疗的疾病进展的影响","authors":"S. Ahmed, J. L. Reguera Ortega, F. Morschhauser, G. Cartron, A. P. Rapoport, K. Izutsu, H. Ghesquieres, M. L. Palomba, H. Goto, J. Kuruvilla, J. S. Abramson, P. Borchmann, U. Jäger, M. Kamdar, M. Bar, M. Strocchia, M. Raggi, R. Nishii, A. M. García-Sancho","doi":"10.1002/hon.70093_142","DOIUrl":null,"url":null,"abstract":"<p><b>Introduction:</b> In the TRANSCEND FL primary analysis, lisocabtagene maraleucel (liso-cel) showed an ORR of 97%, CR rate of 94%, and favorable safety in patients (pts) with second-line (2L) and third-line or later (3L+) R/R FL. In pts with R/R FL, increasing lines of therapy (LOT), progression of disease ≤ 24 mo from initial immunochemotherapy (POD24), and recent exposure to bendamustine (benda) before CAR T cell therapy may impact pt outcomes. We report results in these pt subgroups with R/R FL from TRANSCEND FL.</p><p><b>Methods:</b> Pts had 3L+ R/R FL or 2L R/R FL after prior treatment (tx) with an anti-CD20 antibody and alkylator. All pts with 2L R/R FL had PD ≤ 24 mo of diagnosis (dx) and tx ≤ 6 mo of FL dx, and/or modified GELF criteria. Post hoc subgroup analyses were performed by number of prior LOTs (4L+, 3L, 2L), POD24 (yes, no), and benda exposure (< 12 mo, 12–24 mo, or > 24 mo before leukapheresis or no benda). Outcomes included ORR, CR rate, duration of response (DOR), and PFS (all by IRC), OS, time to next tx (TTNT), and safety. In the benda subgroups, cellular kinetics were assessed.</p><p><b>Results:</b> Of 130 liso-cel–treated pts, 59 (45%) received liso-cel as 4L+ tx, 48 (37%) as 3L tx, and 23 (18%) as 2L tx; 73 (56%) had POD24 and 56 (43%) did not; 11 (8%) had prior benda < 12 mo, 11 (8%) within 12–24 mo, 49 (38%) > 24 mo, and 59 (45%) had no benda. Median on-study follow-up was 29.7 mo (range, 0.3–39.6). There were no major differences in demographics or baseline characteristics among subgroups.</p><p>ORR was ≥ 96% across subgroups (Table). CR rate was similar across prior LOTs and POD24 subgroups, but lower in pts with prior benda < 12 mo (75%) versus other benda subgroups (≥ 95%), though pt numbers were small in the < 12-mo group (<i>n</i> = 8). Median DOR was not reached (NR) in all but 4L+ and POD24 subgroups (30.9 mo each); median PFS was NR in all but 4L+, POD24, and no benda subgroups (31.8 mo each); and median OS was NR for all subgroups. A trend toward better 24-mo DOR, PFS, and OS was observed with liso-cel in earlier versus later LOTs. Median DOR, median PFS, and 24-mo DOR, PFS, and OS were slightly better in pts without POD24, though still clinically meaningful in pts with POD24. Rates of 24-mo DOR, PFS, and OS were high for all benda subgroups (≥ 72%) except for the 8 pts with prior benda < 12 mo where a trend for worse outcomes was observed (24-mo PFS, 50%). Median TTNT was NR for all subgroups; 24-mo rates were numerically lower for pts with 4L+ versus 3L and versus 2L FL, POD24 versus no POD24, and prior benda < 12 mo versus other benda subgroups. Cellular kinetics were similar among benda subgroups. Safety was consistent across subgroups with low rates of grade ≥ 3 cytokine release syndrome and neurological events, and no new signals observed (Table).</p><p><b>Conclusion:</b> These data support the sustained clinical benefit and manageable safety profile of liso-cel in pts with R/R FL, regardless of POD24 status and prior benda exposure, with a trend towards better outcomes when used in earlier LOTs.</p><p><b>Research</b> <b>funding declaration:</b> This study was funded by Celgene, a Bristol-Myers Squibb Company. All authors contributed to and approved the abstract; writing and editorial assistance were provided by Allison Green, PhD, CMPP, of The Lockwood Group (Stamford, CT, USA), funded by Bristol Myers Squibb.</p><p><b>Keywords:</b> cellular therapies; indolent non-Hodgkin lymphoma; ongoing trials</p><p><b>Potential sources of conflict of interest:</b></p><p><b>S. Ahmed</b></p><p><b>Consultant or advisory role:</b> Myeloid Therapeutics, Kite/Gilead</p><p><b>Honoraria:</b> ADC Therapeutics, Genmab, Kite/Gilead</p><p><b>Other remuneration:</b> Research funding: Merck, Chimagen Biosciences, Nektar, Genmab/Seattle Genetics, Janssen Oncology, Caribou Sciences</p><p><b>J. L. Reguera Ortega</b></p><p><b>Consultant or advisory role:</b> Johnson and Johnson, Kite</p><p><b>Honoraria:</b> Speaker's Bureau: Kite, BMS, Amgen, Johnson and Johnson</p><p><b>Other remuneration:</b> Travel expenses: Johnson and Johnson</p><p><b>F. Morschhauser</b></p><p><b>Consultant or advisory role:</b> BMS, Gilead, abbvie, Roche, Janssen</p><p><b>Honoraria:</b> Takeda, chugai, Astra Zeneca</p><p><b>Other remuneration:</b> Advisory board: Roche, Miltenyi, modex therapeutics, astra Zeneca</p><p><b>G. Cartron</b></p><p><b>Consultant or advisory role:</b> BMS, Roche, Onwards Therapeutics, MabQi</p><p><b>Honoraria:</b> Jansen, Takeda, Abbvie, Jansen, Novartis</p><p><b>Other remuneration:</b> Travel support: Roche, Jansen</p><p><b>A. P. Rapoport</b></p><p><b>Other remuneration:</b> National Heart, Lung and Blood Institute DSMB; University of Pennsylvania Abramson Cancer Center DSMB; RapaTherapeutics, DSMB</p><p><b>K. Izutsu</b></p><p><b>Consultant or advisory role:</b> MSD, AstraZeneca, Abbvie, Bristol Myers Squibb, Novartis, Yakult, Kyowa Kirin, Chugai, Beigene, Genmab, Otsuka, Ono Pharma, Mitsubishi Tanabe Pharmaceutical, Eisai, Symbio, Taked, Zenyakua, Carna Biosciences, Nihon Shinyaku</p><p><b>Honoraria:</b> AstraZeneca, Abbvie, Bristol Myers Squibb, Novartis, Pfizer, Janssen, Kyowa Kirin, Daiichi Sankyo, Chugai, Genmab, Gilead, Ono Pharmac, Nihon Kayakueutical, Symbio, Takeda, Lilly, Astellas, Meiji Seika Pharma</p><p><b>Other remuneration:</b> Research funding: MSD, AstraZeneca, Abbvie, Incyte, Bristol Myers Squibb, Novartis, Bayer, Pfizer, Janssen, Yakult, Kyowa Kirin, Daiichi Sankyo, Chugai, Beigene, Genmab, LOXO Oncology, Otsuka, Regeneron, Gilead</p><p><b>H. Ghesquieres</b></p><p><b>Consultant or advisory role:</b> Roche, BMS, Takeda</p><p><b>Honoraria:</b> Gilead, Roche, BMS, Abbvie, Takeda</p><p><b>M. L. Palomba</b></p><p><b>Consultant or advisory role:</b> Synthekine, Kite, Novartis, Bristol Myers Squibb</p><p><b>Other remuneration:</b> Participation on a Data Safety Monitoring Board or Advisory Board: Bristol Myers Squibb</p><p><b>H. Goto</b></p><p><b>Honoraria:</b> Abbvie, BMS, Novartis, Gilead, Chugai, Kyowa Kirin, Takeda, Meiji, MSD</p><p><b>Other remuneration:</b> Research funding: Sanofi, BMS, Gilead, Kyowa Kirin, Symbio</p><p><b>J. Kuruvilla</b></p><p><b>Consultant or advisory role:</b> BMS, Abbvie, BMS, Gilead, Merck, Roche, Seattle Genetics; OmniaBio</p><p><b>Honoraria:</b> BMS, Abbvie, Amgen, Astra Zeneca, Gilead, Incyte, Janssen, Karyopharm, Merck, Novartis, Pfizer, Roche, Seattle Genetics</p><p><b>Other remuneration:</b> Research funding: BMS, Roche, Astra Zeneca, Merck, Novartis; DSMB: Karyopharm; Chair, Scientific Advisory Board: Lymphoma Canada</p><p><b>J. S. Abramson</b></p><p><b>Consultant or advisory role:</b> Celgene, Novartis, Abbvie, Kite/Gilead, EMD Serono, MorphoSys, Alimera Sciences, Karyopharm Therapeutics, Bristol-Myers Squibb, C4 Therapeutics, BeiGene, AstraZeneca, Incyte, Bluebird Bio, Kymera, Epizyme, Genmab, MustangBio, Ono Pharmaceutical, Century Therapeutics, Lilly, Caribou Biosciences, Janssen, Takeda, Interius Biotherapeutics, Cellectar, Seagen, Roche/Genetech, ADC Therapeutics, Foresight Diagnostics</p><p><b>Honoraria:</b> Regeneron, AstraZeneca, Janssen, Bristol-Myers Squibb/Celgene, Abbvie, Kite/Gilead</p><p><b>Other remuneration:</b> Research funding: Seagen, Bristol-Myers Squibb, Cellectics, MustangBio, Regeneron, Merck</p><p><b>P. Borchmann</b></p><p><b>Consultant or advisory role:</b> Takeda Oncology, BMS, Roche, Miltenyi Biotec, Gilead, MSD, Miltenyi Biotec, Gilead, Abbvie, Incyte, Beigene, AstraZeneca</p><p><b>Honoraria:</b> Takeda Oncology, BMS, Roche, MSD</p><p><b>Other remuneration:</b> Grants or contracts: Takeda Oncology, MSD, Incyte, Miltenyi Biotec; Travel Support: Takeda Oncology, Roche, Miltenyi Biotec, Gilead, Incyte, BMS</p><p><b>U. Jäger</b></p><p><b>Consultant or advisory role:</b> GILEAD, Roche, Genzyme</p><p><b>Honoraria:</b> Gilead, Roche, Abbvie, BMS, Novartis, Miltenyi</p><p><b>Other remuneration:</b> Participation on a Data Safety Monitoring Board or Advisory Board: Acerta, Genmab, Genzyme</p><p><b>M. Kamdar</b></p><p><b>Consultant or advisory role:</b> AbbVie, AstraZeneca, Bristol-Myers Squibb, Beigene, Genentech</p><p><b>Other remuneration:</b> Participation on a Data Safety Monitoring Board or Advisory Board: Celgene, Genentech</p><p><b>M. Bar</b></p><p><b>Employment or leadership position:</b> Bristol Myers Squibb</p><p><b>Stock ownership:</b> Bristol Myers Squibb</p><p><b>M. Strocchia</b></p><p><b>Employment or leadership position:</b> Bristol Myers Squibb</p><p><b>Stock ownership:</b> Bristol Myers Squibb</p><p><b>M. Raggi</b></p><p><b>Employment or leadership position:</b> Bristol Myers Squibb</p><p><b>Stock ownership:</b> Bristol Myers Squibb</p><p><b>R. Nishii</b></p><p><b>Employment or leadership position:</b> Bristol Myers Squibb</p><p><b>Stock ownership:</b> Bristol Myers Squibb</p><p><b>A. M. García-Sancho</b></p><p><b>Consultant or advisory role:</b> Abbvie, AstraZeneca, BMS, Genmab, Gilead/Kite, GSK, Ideogen, Incyte, Janssen, Lilly, Miltenyi, Regeneron, Roche, Sobi</p><p><b>Honoraria:</b> Abbvie, AstraZeneca, BeiGene, BMS, Gilead/Kite, Ideogen, Incyte, Janssen, Kyowa Kirin, Lilly, Roche, Sobi, Takeda</p><p><b>Other remuneration:</b> Travel support: Roche, Abbvie, Gilead/Kite, BMS, Lilly; DSMB: AstraZeneca, BMS, Regeneron; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: GELTAMO Foundation</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_142","citationCount":"0","resultStr":"{\"title\":\"LISOCABTAGENE MARALEUCEL IN R/R FL (TRANSCEND FL): IMPACT OF PRIOR LINES OF THERAPY, BENDAMUSTINE EXPOSURE, AND DISEASE PROGRESSION ≤ 24 MONTHS OF INITIAL SYSTEMIC THERAPY\",\"authors\":\"S. Ahmed, J. L. Reguera Ortega, F. Morschhauser, G. Cartron, A. P. Rapoport, K. Izutsu, H. Ghesquieres, M. L. Palomba, H. Goto, J. Kuruvilla, J. S. Abramson, P. Borchmann, U. Jäger, M. Kamdar, M. Bar, M. Strocchia, M. Raggi, R. Nishii, A. M. García-Sancho\",\"doi\":\"10.1002/hon.70093_142\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><b>Introduction:</b> In the TRANSCEND FL primary analysis, lisocabtagene maraleucel (liso-cel) showed an ORR of 97%, CR rate of 94%, and favorable safety in patients (pts) with second-line (2L) and third-line or later (3L+) R/R FL. In pts with R/R FL, increasing lines of therapy (LOT), progression of disease ≤ 24 mo from initial immunochemotherapy (POD24), and recent exposure to bendamustine (benda) before CAR T cell therapy may impact pt outcomes. We report results in these pt subgroups with R/R FL from TRANSCEND FL.</p><p><b>Methods:</b> Pts had 3L+ R/R FL or 2L R/R FL after prior treatment (tx) with an anti-CD20 antibody and alkylator. All pts with 2L R/R FL had PD ≤ 24 mo of diagnosis (dx) and tx ≤ 6 mo of FL dx, and/or modified GELF criteria. Post hoc subgroup analyses were performed by number of prior LOTs (4L+, 3L, 2L), POD24 (yes, no), and benda exposure (< 12 mo, 12–24 mo, or > 24 mo before leukapheresis or no benda). Outcomes included ORR, CR rate, duration of response (DOR), and PFS (all by IRC), OS, time to next tx (TTNT), and safety. In the benda subgroups, cellular kinetics were assessed.</p><p><b>Results:</b> Of 130 liso-cel–treated pts, 59 (45%) received liso-cel as 4L+ tx, 48 (37%) as 3L tx, and 23 (18%) as 2L tx; 73 (56%) had POD24 and 56 (43%) did not; 11 (8%) had prior benda < 12 mo, 11 (8%) within 12–24 mo, 49 (38%) > 24 mo, and 59 (45%) had no benda. Median on-study follow-up was 29.7 mo (range, 0.3–39.6). There were no major differences in demographics or baseline characteristics among subgroups.</p><p>ORR was ≥ 96% across subgroups (Table). CR rate was similar across prior LOTs and POD24 subgroups, but lower in pts with prior benda < 12 mo (75%) versus other benda subgroups (≥ 95%), though pt numbers were small in the < 12-mo group (<i>n</i> = 8). Median DOR was not reached (NR) in all but 4L+ and POD24 subgroups (30.9 mo each); median PFS was NR in all but 4L+, POD24, and no benda subgroups (31.8 mo each); and median OS was NR for all subgroups. A trend toward better 24-mo DOR, PFS, and OS was observed with liso-cel in earlier versus later LOTs. Median DOR, median PFS, and 24-mo DOR, PFS, and OS were slightly better in pts without POD24, though still clinically meaningful in pts with POD24. Rates of 24-mo DOR, PFS, and OS were high for all benda subgroups (≥ 72%) except for the 8 pts with prior benda < 12 mo where a trend for worse outcomes was observed (24-mo PFS, 50%). Median TTNT was NR for all subgroups; 24-mo rates were numerically lower for pts with 4L+ versus 3L and versus 2L FL, POD24 versus no POD24, and prior benda < 12 mo versus other benda subgroups. Cellular kinetics were similar among benda subgroups. Safety was consistent across subgroups with low rates of grade ≥ 3 cytokine release syndrome and neurological events, and no new signals observed (Table).</p><p><b>Conclusion:</b> These data support the sustained clinical benefit and manageable safety profile of liso-cel in pts with R/R FL, regardless of POD24 status and prior benda exposure, with a trend towards better outcomes when used in earlier LOTs.</p><p><b>Research</b> <b>funding declaration:</b> This study was funded by Celgene, a Bristol-Myers Squibb Company. All authors contributed to and approved the abstract; writing and editorial assistance were provided by Allison Green, PhD, CMPP, of The Lockwood Group (Stamford, CT, USA), funded by Bristol Myers Squibb.</p><p><b>Keywords:</b> cellular therapies; indolent non-Hodgkin lymphoma; ongoing trials</p><p><b>Potential sources of conflict of interest:</b></p><p><b>S. Ahmed</b></p><p><b>Consultant or advisory role:</b> Myeloid Therapeutics, Kite/Gilead</p><p><b>Honoraria:</b> ADC Therapeutics, Genmab, Kite/Gilead</p><p><b>Other remuneration:</b> Research funding: Merck, Chimagen Biosciences, Nektar, Genmab/Seattle Genetics, Janssen Oncology, Caribou Sciences</p><p><b>J. L. Reguera Ortega</b></p><p><b>Consultant or advisory role:</b> Johnson and Johnson, Kite</p><p><b>Honoraria:</b> Speaker's Bureau: Kite, BMS, Amgen, Johnson and Johnson</p><p><b>Other remuneration:</b> Travel expenses: Johnson and Johnson</p><p><b>F. Morschhauser</b></p><p><b>Consultant or advisory role:</b> BMS, Gilead, abbvie, Roche, Janssen</p><p><b>Honoraria:</b> Takeda, chugai, Astra Zeneca</p><p><b>Other remuneration:</b> Advisory board: Roche, Miltenyi, modex therapeutics, astra Zeneca</p><p><b>G. Cartron</b></p><p><b>Consultant or advisory role:</b> BMS, Roche, Onwards Therapeutics, MabQi</p><p><b>Honoraria:</b> Jansen, Takeda, Abbvie, Jansen, Novartis</p><p><b>Other remuneration:</b> Travel support: Roche, Jansen</p><p><b>A. P. Rapoport</b></p><p><b>Other remuneration:</b> National Heart, Lung and Blood Institute DSMB; University of Pennsylvania Abramson Cancer Center DSMB; RapaTherapeutics, DSMB</p><p><b>K. Izutsu</b></p><p><b>Consultant or advisory role:</b> MSD, AstraZeneca, Abbvie, Bristol Myers Squibb, Novartis, Yakult, Kyowa Kirin, Chugai, Beigene, Genmab, Otsuka, Ono Pharma, Mitsubishi Tanabe Pharmaceutical, Eisai, Symbio, Taked, Zenyakua, Carna Biosciences, Nihon Shinyaku</p><p><b>Honoraria:</b> AstraZeneca, Abbvie, Bristol Myers Squibb, Novartis, Pfizer, Janssen, Kyowa Kirin, Daiichi Sankyo, Chugai, Genmab, Gilead, Ono Pharmac, Nihon Kayakueutical, Symbio, Takeda, Lilly, Astellas, Meiji Seika Pharma</p><p><b>Other remuneration:</b> Research funding: MSD, AstraZeneca, Abbvie, Incyte, Bristol Myers Squibb, Novartis, Bayer, Pfizer, Janssen, Yakult, Kyowa Kirin, Daiichi Sankyo, Chugai, Beigene, Genmab, LOXO Oncology, Otsuka, Regeneron, Gilead</p><p><b>H. Ghesquieres</b></p><p><b>Consultant or advisory role:</b> Roche, BMS, Takeda</p><p><b>Honoraria:</b> Gilead, Roche, BMS, Abbvie, Takeda</p><p><b>M. L. Palomba</b></p><p><b>Consultant or advisory role:</b> Synthekine, Kite, Novartis, Bristol Myers Squibb</p><p><b>Other remuneration:</b> Participation on a Data Safety Monitoring Board or Advisory Board: Bristol Myers Squibb</p><p><b>H. Goto</b></p><p><b>Honoraria:</b> Abbvie, BMS, Novartis, Gilead, Chugai, Kyowa Kirin, Takeda, Meiji, MSD</p><p><b>Other remuneration:</b> Research funding: Sanofi, BMS, Gilead, Kyowa Kirin, Symbio</p><p><b>J. Kuruvilla</b></p><p><b>Consultant or advisory role:</b> BMS, Abbvie, BMS, Gilead, Merck, Roche, Seattle Genetics; OmniaBio</p><p><b>Honoraria:</b> BMS, Abbvie, Amgen, Astra Zeneca, Gilead, Incyte, Janssen, Karyopharm, Merck, Novartis, Pfizer, Roche, Seattle Genetics</p><p><b>Other remuneration:</b> Research funding: BMS, Roche, Astra Zeneca, Merck, Novartis; DSMB: Karyopharm; Chair, Scientific Advisory Board: Lymphoma Canada</p><p><b>J. S. Abramson</b></p><p><b>Consultant or advisory role:</b> Celgene, Novartis, Abbvie, Kite/Gilead, EMD Serono, MorphoSys, Alimera Sciences, Karyopharm Therapeutics, Bristol-Myers Squibb, C4 Therapeutics, BeiGene, AstraZeneca, Incyte, Bluebird Bio, Kymera, Epizyme, Genmab, MustangBio, Ono Pharmaceutical, Century Therapeutics, Lilly, Caribou Biosciences, Janssen, Takeda, Interius Biotherapeutics, Cellectar, Seagen, Roche/Genetech, ADC Therapeutics, Foresight Diagnostics</p><p><b>Honoraria:</b> Regeneron, AstraZeneca, Janssen, Bristol-Myers Squibb/Celgene, Abbvie, Kite/Gilead</p><p><b>Other remuneration:</b> Research funding: Seagen, Bristol-Myers Squibb, Cellectics, MustangBio, Regeneron, Merck</p><p><b>P. Borchmann</b></p><p><b>Consultant or advisory role:</b> Takeda Oncology, BMS, Roche, Miltenyi Biotec, Gilead, MSD, Miltenyi Biotec, Gilead, Abbvie, Incyte, Beigene, AstraZeneca</p><p><b>Honoraria:</b> Takeda Oncology, BMS, Roche, MSD</p><p><b>Other remuneration:</b> Grants or contracts: Takeda Oncology, MSD, Incyte, Miltenyi Biotec; Travel Support: Takeda Oncology, Roche, Miltenyi Biotec, Gilead, Incyte, BMS</p><p><b>U. Jäger</b></p><p><b>Consultant or advisory role:</b> GILEAD, Roche, Genzyme</p><p><b>Honoraria:</b> Gilead, Roche, Abbvie, BMS, Novartis, Miltenyi</p><p><b>Other remuneration:</b> Participation on a Data Safety Monitoring Board or Advisory Board: Acerta, Genmab, Genzyme</p><p><b>M. Kamdar</b></p><p><b>Consultant or advisory role:</b> AbbVie, AstraZeneca, Bristol-Myers Squibb, Beigene, Genentech</p><p><b>Other remuneration:</b> Participation on a Data Safety Monitoring Board or Advisory Board: Celgene, Genentech</p><p><b>M. Bar</b></p><p><b>Employment or leadership position:</b> Bristol Myers Squibb</p><p><b>Stock ownership:</b> Bristol Myers Squibb</p><p><b>M. Strocchia</b></p><p><b>Employment or leadership position:</b> Bristol Myers Squibb</p><p><b>Stock ownership:</b> Bristol Myers Squibb</p><p><b>M. Raggi</b></p><p><b>Employment or leadership position:</b> Bristol Myers Squibb</p><p><b>Stock ownership:</b> Bristol Myers Squibb</p><p><b>R. Nishii</b></p><p><b>Employment or leadership position:</b> Bristol Myers Squibb</p><p><b>Stock ownership:</b> Bristol Myers Squibb</p><p><b>A. M. García-Sancho</b></p><p><b>Consultant or advisory role:</b> Abbvie, AstraZeneca, BMS, Genmab, Gilead/Kite, GSK, Ideogen, Incyte, Janssen, Lilly, Miltenyi, Regeneron, Roche, Sobi</p><p><b>Honoraria:</b> Abbvie, AstraZeneca, BeiGene, BMS, Gilead/Kite, Ideogen, Incyte, Janssen, Kyowa Kirin, Lilly, Roche, Sobi, Takeda</p><p><b>Other remuneration:</b> Travel support: Roche, Abbvie, Gilead/Kite, BMS, Lilly; DSMB: AstraZeneca, BMS, Regeneron; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: GELTAMO Foundation</p>\",\"PeriodicalId\":12882,\"journal\":{\"name\":\"Hematological Oncology\",\"volume\":\"43 S3\",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-06-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_142\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hematological Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/hon.70093_142\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematological Oncology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/hon.70093_142","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
LISOCABTAGENE MARALEUCEL IN R/R FL (TRANSCEND FL): IMPACT OF PRIOR LINES OF THERAPY, BENDAMUSTINE EXPOSURE, AND DISEASE PROGRESSION ≤ 24 MONTHS OF INITIAL SYSTEMIC THERAPY
Introduction: In the TRANSCEND FL primary analysis, lisocabtagene maraleucel (liso-cel) showed an ORR of 97%, CR rate of 94%, and favorable safety in patients (pts) with second-line (2L) and third-line or later (3L+) R/R FL. In pts with R/R FL, increasing lines of therapy (LOT), progression of disease ≤ 24 mo from initial immunochemotherapy (POD24), and recent exposure to bendamustine (benda) before CAR T cell therapy may impact pt outcomes. We report results in these pt subgroups with R/R FL from TRANSCEND FL.
Methods: Pts had 3L+ R/R FL or 2L R/R FL after prior treatment (tx) with an anti-CD20 antibody and alkylator. All pts with 2L R/R FL had PD ≤ 24 mo of diagnosis (dx) and tx ≤ 6 mo of FL dx, and/or modified GELF criteria. Post hoc subgroup analyses were performed by number of prior LOTs (4L+, 3L, 2L), POD24 (yes, no), and benda exposure (< 12 mo, 12–24 mo, or > 24 mo before leukapheresis or no benda). Outcomes included ORR, CR rate, duration of response (DOR), and PFS (all by IRC), OS, time to next tx (TTNT), and safety. In the benda subgroups, cellular kinetics were assessed.
Results: Of 130 liso-cel–treated pts, 59 (45%) received liso-cel as 4L+ tx, 48 (37%) as 3L tx, and 23 (18%) as 2L tx; 73 (56%) had POD24 and 56 (43%) did not; 11 (8%) had prior benda < 12 mo, 11 (8%) within 12–24 mo, 49 (38%) > 24 mo, and 59 (45%) had no benda. Median on-study follow-up was 29.7 mo (range, 0.3–39.6). There were no major differences in demographics or baseline characteristics among subgroups.
ORR was ≥ 96% across subgroups (Table). CR rate was similar across prior LOTs and POD24 subgroups, but lower in pts with prior benda < 12 mo (75%) versus other benda subgroups (≥ 95%), though pt numbers were small in the < 12-mo group (n = 8). Median DOR was not reached (NR) in all but 4L+ and POD24 subgroups (30.9 mo each); median PFS was NR in all but 4L+, POD24, and no benda subgroups (31.8 mo each); and median OS was NR for all subgroups. A trend toward better 24-mo DOR, PFS, and OS was observed with liso-cel in earlier versus later LOTs. Median DOR, median PFS, and 24-mo DOR, PFS, and OS were slightly better in pts without POD24, though still clinically meaningful in pts with POD24. Rates of 24-mo DOR, PFS, and OS were high for all benda subgroups (≥ 72%) except for the 8 pts with prior benda < 12 mo where a trend for worse outcomes was observed (24-mo PFS, 50%). Median TTNT was NR for all subgroups; 24-mo rates were numerically lower for pts with 4L+ versus 3L and versus 2L FL, POD24 versus no POD24, and prior benda < 12 mo versus other benda subgroups. Cellular kinetics were similar among benda subgroups. Safety was consistent across subgroups with low rates of grade ≥ 3 cytokine release syndrome and neurological events, and no new signals observed (Table).
Conclusion: These data support the sustained clinical benefit and manageable safety profile of liso-cel in pts with R/R FL, regardless of POD24 status and prior benda exposure, with a trend towards better outcomes when used in earlier LOTs.
Researchfunding declaration: This study was funded by Celgene, a Bristol-Myers Squibb Company. All authors contributed to and approved the abstract; writing and editorial assistance were provided by Allison Green, PhD, CMPP, of The Lockwood Group (Stamford, CT, USA), funded by Bristol Myers Squibb.
Other remuneration: Travel support: Roche, Abbvie, Gilead/Kite, BMS, Lilly; DSMB: AstraZeneca, BMS, Regeneron; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: GELTAMO Foundation
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Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged:
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