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

Abstract

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.

Research funding 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.

Keywords: cellular therapies; indolent non-Hodgkin lymphoma; ongoing trials

Potential sources of conflict of interest:

S. Ahmed

Consultant or advisory role: Myeloid Therapeutics, Kite/Gilead

Honoraria: ADC Therapeutics, Genmab, Kite/Gilead

Other remuneration: Research funding: Merck, Chimagen Biosciences, Nektar, Genmab/Seattle Genetics, Janssen Oncology, Caribou Sciences

J. L. Reguera Ortega

Consultant or advisory role: Johnson and Johnson, Kite

Honoraria: Speaker's Bureau: Kite, BMS, Amgen, Johnson and Johnson

Other remuneration: Travel expenses: Johnson and Johnson

F. Morschhauser

Consultant or advisory role: BMS, Gilead, abbvie, Roche, Janssen

Honoraria: Takeda, chugai, Astra Zeneca

Other remuneration: Advisory board: Roche, Miltenyi, modex therapeutics, astra Zeneca

G. Cartron

Consultant or advisory role: BMS, Roche, Onwards Therapeutics, MabQi

Honoraria: Jansen, Takeda, Abbvie, Jansen, Novartis

Other remuneration: Travel support: Roche, Jansen

A. P. Rapoport

Other remuneration: National Heart, Lung and Blood Institute DSMB; University of Pennsylvania Abramson Cancer Center DSMB; RapaTherapeutics, DSMB

K. Izutsu

Consultant or advisory role: 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

Honoraria: 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

Other remuneration: 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

H. Ghesquieres

Consultant or advisory role: Roche, BMS, Takeda

Honoraria: Gilead, Roche, BMS, Abbvie, Takeda

M. L. Palomba

Consultant or advisory role: Synthekine, Kite, Novartis, Bristol Myers Squibb

Other remuneration: Participation on a Data Safety Monitoring Board or Advisory Board: Bristol Myers Squibb

H. Goto

Honoraria: Abbvie, BMS, Novartis, Gilead, Chugai, Kyowa Kirin, Takeda, Meiji, MSD

Other remuneration: Research funding: Sanofi, BMS, Gilead, Kyowa Kirin, Symbio

J. Kuruvilla

Consultant or advisory role: BMS, Abbvie, BMS, Gilead, Merck, Roche, Seattle Genetics; OmniaBio

Honoraria: BMS, Abbvie, Amgen, Astra Zeneca, Gilead, Incyte, Janssen, Karyopharm, Merck, Novartis, Pfizer, Roche, Seattle Genetics

Other remuneration: Research funding: BMS, Roche, Astra Zeneca, Merck, Novartis; DSMB: Karyopharm; Chair, Scientific Advisory Board: Lymphoma Canada

J. S. Abramson

Consultant or advisory role: 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

Honoraria: Regeneron, AstraZeneca, Janssen, Bristol-Myers Squibb/Celgene, Abbvie, Kite/Gilead

Other remuneration: Research funding: Seagen, Bristol-Myers Squibb, Cellectics, MustangBio, Regeneron, Merck

P. Borchmann

Consultant or advisory role: Takeda Oncology, BMS, Roche, Miltenyi Biotec, Gilead, MSD, Miltenyi Biotec, Gilead, Abbvie, Incyte, Beigene, AstraZeneca

Honoraria: Takeda Oncology, BMS, Roche, MSD

Other remuneration: Grants or contracts: Takeda Oncology, MSD, Incyte, Miltenyi Biotec; Travel Support: Takeda Oncology, Roche, Miltenyi Biotec, Gilead, Incyte, BMS

U. Jäger

Consultant or advisory role: GILEAD, Roche, Genzyme

Honoraria: Gilead, Roche, Abbvie, BMS, Novartis, Miltenyi

Other remuneration: Participation on a Data Safety Monitoring Board or Advisory Board: Acerta, Genmab, Genzyme

M. Kamdar

Consultant or advisory role: AbbVie, AstraZeneca, Bristol-Myers Squibb, Beigene, Genentech

Other remuneration: Participation on a Data Safety Monitoring Board or Advisory Board: Celgene, Genentech

M. Bar

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

M. Strocchia

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

M. Raggi

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

R. Nishii

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

A. M. García-Sancho

Consultant or advisory role: Abbvie, AstraZeneca, BMS, Genmab, Gilead/Kite, GSK, Ideogen, Incyte, Janssen, Lilly, Miltenyi, Regeneron, Roche, Sobi

Honoraria: Abbvie, AstraZeneca, BeiGene, BMS, Gilead/Kite, Ideogen, Incyte, Janssen, Kyowa Kirin, Lilly, Roche, Sobi, Takeda

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