LISOCABTAGENE MARALEUCEL (LISO-CEL) IN PATIENTS (PTS) WITH RELAPSED OR REFRACTORY (R/R) MARGINAL ZONE LYMPHOMA (MZL) IN THE PHASE 2 TRANSCEND FL STUDY

Abstract

Introduction: There remains an unmet need for effective and safe treatment options for pts with R/R MZL. TRANSCEND FL (NCT04245839) is a global, phase 2, single-arm, multicohort study that evaluates the efficacy and safety of the anti-CD19 CAR T cell therapy, liso-cel, in pts with R/R FL or MZL. Here, we present the primary analysis in pts with R/R (third-line or later) MZL.

Methods: Pts with R/R MZL who received ≥ 2 prior lines of systemic therapy, including a combination of an anti-CD20 antibody and an alkylating agent, or had relapsed disease after HSCT were eligible. Pts received liso-cel (100 × 10⁶ CAR⁺ T cells) after lymphodepleting chemotherapy (LDC). Bridging therapy was allowed, but reconfirmation of measurable disease was needed before LDC. The primary endpoint of ORR per independent review committee by CT using Lugano 2014 criteria (null hypothesis [H₀]: ≤ 50%) and key secondary endpoint of CR rate (H₀: ≤ 5%) were tested hierarchically.

Results: At data cutoff, 77 pts were leukapheresed, 67 (87%) received liso-cel (safety set), and 66 (86%) were efficacy evaluable. Median (range) age was 62 y (37–81), 85% had Ann Arbor stage III/IV disease, 36% had progression of disease ≤ 24 mo of initiation of first-line immunochemotherapy, 39% had refractory disease, and 22% had bulky disease. MZL subtypes included nodal (48%), splenic (27%), and extranodal/mucosa-associated lymphoid tissue (25%). Median (range) prior lines of therapy was 3 (2–18). Median (range) on-study follow-up was 24.1 mo (1.1–43.0). The primary endpoint of ORR was met at 95.5% (95% CI: 87.3–99.1; 1-sided p < 0.0001; Table). The secondary endpoint of CR rate was also met at 62.1% (95% CI: 49.3–73.8; 1-sided p < 0.0001; Table). With a median follow-up of 21.6, 23.8, and 24.5 mo, respectively, the 24-mo rates were 88.6% for DOR (89.0% in pts with CR), 85.7% for PFS, and 90.4% for OS (Table).

All pts had any-grade (gr) treatment-emergent adverse events (TEAE; gr ≥ 3, 88%). Cytokine release syndrome (CRS) occurred in 76% of pts (gr 3, 4%; no gr 4–5) and neurological events (NE) in 33% (gr 3, 4%; no gr 4–5; Table). For CRS/NE management, 33% of pts received both tocilizumab and corticosteroids, 21% received tocilizumab only, and 6% received corticosteroids only. Prolonged cytopenia (gr ≥ 3 laboratory values at Day 29) occurred in 42% of pts (anemia, 9%; neutropenia, 27%; thrombocytopenia, 25%), gr ≥ 3 infection in 9%, and MAS-HLH in 4% (all gr 3 and resolved). Two grade 5 TEAEs occurred (1 on Day 32, pt had T-cell lymphoma [TCL]; 1 on Day 47, pt had neutropenic sepsis). Liso-cel transgene testing and integration site analysis suggested that the TCL was unrelated to liso-cel.

Conclusion: In pts with R/R MZL, liso-cel demonstrated deep and durable responses with high survival rates at 24 mo. The safety profile of liso-cel was manageable, with low rates of gr 3 CRS/NE (no gr 4–5), consistent with prior reports. These results support liso-cel as a potential treatment option for pts with R/R MZL.

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 Bu Reinen, PhD, CMPP, of The Lockwood Group (Stamford, CT, USA), funded by Bristol Myers Squibb.

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

Potential sources of conflict of interest:

M. L. Palomba

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

Other remuneration: Participation in DSMB or Advisory Board: BMS

S. J. Schuster

Honoraria: Incyte/Morphosys, Takeda

Other remuneration: Membership on an entity's Board of Directors or advisory committees: Nordic Nanovector, Mustang Bio, Novartis, Legend Biotech, Kite, Genmab, Incyte/Morphosys, Abbvie, AstraZeneca, BeiGene, Caribou Biotech; DSMB: Fate Therapeutics; Research funding: Genentech/Roche, Genmab

R. Karmali

Consultant or advisory role: BeiGen, BMS, Genentech/Roche, Gilead/Kite, Abbvie, Lilly Onc, Genmab, Miltenyi

Honoraria: Astrazeneca, BeiGene, BMS, Incyte/Morphosys

Other remuneration: Participation on a Data Safety Monitoring Board or Advisory Board: Calithera, Avencell; ASH committee on Quality; ASCO NCCN guideline committee for histiocytic disorders

A. P. Skarbnik

Consultant or advisory role: AstraZeneca, Abbvie, Alexion, Bristol-Myers-Squibb, Celgene, Epizyme, Genentech, GenMab, Jazz Pharmaceuticals, Kite Pharma, Lilly, Janssen, MorphoSys, Novartis, SeaGen, Beigene

Honoraria: AstraZeneca, Abbvie, Bristol Myers Squibb, Genentech, GenMab, Jazz Pharmaceuticals, ADC Therapeutics, Kite Pharma, Lilly, Janssen, Seagen

Other remuneration: Speaker Bureau fees: Bristol Myers Squibb; Participation on a Data Safety Monitoring Board or Advisory Board: Alexion, Bristol Myers Squibb

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 Sciences, Janssen, Takeda, Interius Biotherapeutics, Cellectar, Seagen, Roche/Genetech, ADC Therapeutics, Foresight Diagnostics

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

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

K. Ardeshna

Other remuneration: Travel support: Novartis, Gilead, Bristol Myers Squibb

P. Borchmann

Consultant or advisory role: Takeda Oncology, BMS, Roche, Miltenyi Biotec, Gilead, MSD

Honoraria: Takeda Oncology, BMS, Roche, MSD, Miltenyi Biotec, Gilead, Abbvie, Incyte, Beigene, AstraZeneca

Other remuneration: Grants paid to institution: Takeda Oncology MSD, Incyte, Miltenyi Biotec. Travel support: Takeda Oncology, Roche, Miltenyi Biotec, Gilead, Incyte, BMS

B. T. Hill

Consultant or advisory role: Bristol Myers Squibb

Other remuneration: Research funding: Bristol Myers Squibb

A. M. Garcia-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; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: GELTAMO Foundation

A. Pinto

Stock ownership: Autolus Therapeutics, IGM Biosciences]

Honoraria: Hoffmann-La Roche AG, Ely-Lilly, Merck Sharp and Dohme, Bristol-Meyers Squibb, SOBI, Abbvie

Other remuneration: Support for attending meetings and/or travel: Hoffmann-La Roche AG, Ely-Lilly, SOBI; Participation on a Data Safety Monitoring Board or Advisory Board: Hoffmann-La Roche AG, Ely-Lilly, Merck Sharp and Dohme, Bristol-Meyers Squibb, SOBI, Abbvie, Takeda

A. P. Rapoport

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

G. Cartron

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

Honoraria: Jansen, Takeda, Abbvie, Jansen, Novartis

Other remuneration: Support for attending meetings and/or travel: Roche, Janssen

I. Fleury

Consultant or advisory role: Abbvie, AstraZeneca, Beigene, BMS, Incyte, Janssen, Kite-Gilead, Merck, Novartis, Roche, Seagen, Takeda

Honoraria: Speaker bureau : Abbvie, Astrazeneca, Beigene, BMS, Incyte, Janssen, Kite-Gilead, Novartis, Roche, Seagen

Other remuneration: Support for attending meetings and/or travel: Abbvie, AstraZeneca, Beigene, Kite-Gilead, Roche, Seagen

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

M. Kamdar

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

Other remuneration: DMC: Celgene, Genentech

S. Mielke

Honoraria: Celgene/BMS, Novartis, Janssen

Other remuneration: Grants: KITE/GILEAD; Participation on a Data Safety Monitoring Board or Advisory Board: Miltenyi, Immunicum/Mendes, DSMB via my institution; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: SWECARNETFounder/leadership

A. M. Barbui

Other remuneration: Grants: Pierra Fabre, Incyte, Rocher

J. L. Reguera Ortega

Consultant or advisory role: Johnson and Johnson, Kite

Educational grants: Johnson and Johnson

Other remuneration: Speaker's Bureau: Kite, BMS, Amgen, Johnson and Johnson

L. J. Nastoupil

Honoraria: AstraZeneca, Regeneron, Merck

Other remuneration: Research support & Honorarium: Daiichi Sankyo, Genentech, Gilead/Kite, Janssen, Incyte, Novartis, Takeda,

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 Biosciences,

M. Bar

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

L. Diaz

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

V. Diab

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

M. Vedal

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

S. Colicino

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

A. Avilion

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

F. Morschhauser

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

Honoraria: Takeda, chugai, AstraZeneca

Other remuneration: Participation on a Data Safety Monitoring Board or Advisory Board: Roche, Miltenyi, Modex Therapeutics, AstraZeneca