Dropping Bombs: � WMLDs in Lymphoma��
Matt Lunning D.O. F.A.C.P.
Associate Professor
Fred & Pamela Buffett Cancer Center
Medical Director Gene &Cellular Therapy, NM
Assistant Vice-Chair Research Department of Medicine
Assistant Vice Chancellor of Clinical Research
University of Nebraska Medical Center
Omaha, NE
Disclosures
Updated 3/2025 | |
Research Support | AbbVie, FATE Therapeutics; Genentech; BMS; |
Consultancy | AbbVie, Acrotech, ADC Therapeutics, Astra-Zeneca, BMS, FATE, Genentech, Ipsen, J&J, Kite, LOXO, Pfizer, Recordati, Veeva; |
Employment | NONE |
Stock/Equity | NONE |
Speakers Bureau | NONE |
CD19+ in Hematologic Malignancies
*Sparing of hematopoietic stem cell+
What Have We Made?
WMLD
NHL
Hyperuricemia
Hyperkalemia
Neutropenia
Transfusions
Infections
CRS
ICANS
Aplasia
Risk = Reward
WMLD
LBCL
Hyperuricemia
Hyperkalemia
Neutropenia
Transfusions
Infections
CRS
ICANS
Aplasia
Relapsed/Refractory DLBCL
Crump et al. Blood 2017
Axi-Cel & Liso-cel: Excitement Generation
Neelapu et al. NEJM 2018; Abramson Lancet 2022
High Risk 2L DLBCL�
1. Locke FL, et al. N Engl J Med. 2022;386(7):640-654. 2. Westin J, et al. N Engl J Med. 2023;389(2):148-157. �3. Kamdar M, et al. Lancet. 2022;399(10343):2294-2308. 4. Bishop M, et al. N Engl J Med. 2022;386(7):629-639.
10
EFS | ZUMA-7: EFS1,2 | TRANSFORM: EFS3 | BELINDA: EFS4 | |||
Axi-Cel (n=180) | SOC (n=179) | Liso-Cel (n=92) | SOC (n=92) | Tisa-Cel (n=162) | SOC (n=160) | |
Median (95% CI) | 8.3 (4.5-15.8) | 2.0 (1.6-2.8) | 10.1 (6.1-NR) | 2.3 (2.2-4.3) | 3.0 (2.9-4.2) | 3.0 (3.0-3.5) |
HR (95% CI); �P value | 0.40 (0.31-0.51);� <0.001 | 0.35 (0.23-0.53); �<0.0001 | 1.07 (0.82-1.40); �0.61 | |||
ZUMA-7: EFS1,2
TRANSFORM: EFS3
BELINDA: EFS4
10
ZUMA-7 Overall Survival!�
Westin JR, et al. N Engl J Med. 2023.
Putting Txp To Bed
Locke FL, et al. ASH 2021. Abstract 2
PILOT Study
Sehgal A, et al. ASCO 2022. Abstract 7062.
PILOT Study
Sehgal A, et al. ASCO 2022. Abstract 7062.
Impact of CRS/ICANS
Factor | Axi-Cel (ZUMA-7)1 | Liso-Cel (TRANSFORM)2 | ||
Axi-Cel �(n=170) | SOC (n=168) | Liso-Cel (n=92) | SOC (n=91) | |
Any grade CRS, % Grade ≥3 CRS Median time to onset, day Median duration, day | 92 6 3 7 | - | 49 1 5 4 | - |
Any grade neurologic event, % Grade ≥3 neurologic event Median time to onset, day Median duration, day | 60 21 7 9 | 20 1 23 23 | 12 4 11 6 | - |
Grade ≥3 infections, % | 14 | 11 | 15 | 21 |
1. Locke FL, et al. N Engl J Med. 2022;386(7):640-654. 2. Kamdar M, et al. Lancet. 2022;399(10343):2294-2308. �
WMLD
FL
Hyperuricemia
Hyperkalemia
Neutropenia
Transfusions
Infections
CRS
ICANS
Aplasia
�Axi-cel in Rel/Ref FL: ZUMA-5
Jacobsen et al. 2022
17
�Axi-cel in Rel/Ref FL: ZUMA-5
Jacobsen Lancet 2022; Neelapu et al. Blood 2024; Neelapu et al ASH 2024 Abs 864
:
5-year f/u
DOR: 60%
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�ZUMA-5 vs SCHOLAR-5
Ghone et al. Blood 2022
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�Tisa-cel in Rel/Ref FL: ELARA
Dreyling et al. Blood 2024
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�Tisa-cel in Rel/Ref FL: ELARA
Dreyling et al. Blood 2024
Estimated 66% in CR were progression free at 48 months
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�Tisa-cel in Rel/Ref FL: ELARA
Salles et al. Blood Advances 2022; Landsburg et al. ASH 2024 Abs 4398
CIBMTR Data (N=92) with 6.7 mo f/u
6 month PFS: 79%
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�Liso-cel in Rel/Ref FL: TRANSCEND-FL
Morschhauser et al. Nat Med 2024
Patient Characteristics | 2L FL (n=23) | 3L+ FL (n=107) | |
Median age (range), y | 53 (34–69) | 62 (23–80) | |
FL grade 1 or 2/3a at screening, n (%) | 17 (74)/6 (26) | 81 (76)/25 (23) | |
Ann Arbor stage at screening, n (%) | I/II | 6 (26) | 12 (11) |
III/IV | 17 (74) | 95 (89) | |
FLIPI at screening, n (%) | 0–1/2 | 11 (48)/4 (17) | 12 (11)/34 (32) |
3–5 | 8 (35) | 61 (57) | |
LDH>ULN before LDC, n (%) | 6 (26) | 47 (44) | |
Met mGELF criteria at most recent relapse, n (%) | 16 (70) | 57 (53) | |
Median (range) prior lines of therapy | 1 (1–1) | 3 (2–10) | |
Prior HSCT, n (%) | 0 | 33 (31) | |
Received prior rituximab and lenalidomide, n (%) | 0 | 23 (21) | |
Refractory to last systemic therapy, n (%) | 15 (65) | 72 (67) | |
Double refractory (anti-CD20 & alkylator),d n (%) | 11 (48) | 69 (64) | |
POD24 from initial immunochemotherapy, n (%) | 15 (65) | 58 (54) | |
POD24 from diagnosis, n (%) | 12 (52) | 46 (43) | |
Received bridging therapy, n (%) | 5 (22) | 44 (41) | |
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�Liso-cel in Rel/Ref FL: TRANSCEND-FL
Morschhauser et al. Nat Med 2024; Nastoupil et al. ASH 2024 Abs 4387
| ORR | CR | DOR |
2L FL | 96% | 96% | 75% |
3L+ FL | 97% | 94% | 86% |
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Dropping Bombs in FL
Neelapua et al. Blood 2024; Dreyling et al. Blood 2024; Morschhauser et al. Nat Med 2024; Neelapu et al ASH 2024 Abs 864 Nastoupil et al. ASH 2024 Abs 4387
| Axi-cel | Tisa-cel | Liso-cel |
Patients | 124 | 97 | 101 |
ORR | 94% | 86% | 97% |
CR | 79% | 68% | 94% |
mF/U | 66m | 29m | 30m |
Median PFS | 57m (50%@60m) | 55m (75%@12m) | NR @30m (3L+:73% @30m) (2L: 83% @ 30m) |
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Do they Taste Different?
Neelapua et al. Blood 2024; Dreyling et al. Blood 2024; Morschhauser et al. Nat Med 2024
| Axi-cel | Tisa-cel | Liso-cel |
CRS (All Grade) | 78% | 49% | 58% |
| 6% | 0% | 1% |
ICANS (All Grade) | 56% | 23% | 15% |
| 18% | 1% | 2% |
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WMLD
MCL
Hyperuricemia
Hyperkalemia
Neutropenia
Transfusions
Infections
CRS
ICANS
Aplasia
�Brexu-cel in Rel/Ref MCL: ZUMA-2
Wang et al. NEJM 2020
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�Brexu-cel in Rel/Ref MCL: ZUMA-2 (Cohort 1)
Wang et al. NEJM 2020; Wang et al. ASH 2024 Abs 4388
:
68 mo f/u
mDOR: 37 mo (all CRs)
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�Brexu-cel in Rel/Ref MCL: ZUMA-2 (Cohort 3)
Wang et al. NEJM 2020 ; van Meerten et al. ASH 2024 Abs 748
N=95 (BTKi naïve)
73% CR
mPFS: 27 mo
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�Liso-cel in Rel/Ref MCL: TRANSCEND-MCL
Wang et al. JCO 2024
31
Hidden Ingredient�Liso-cel in Rel/Ref MCL: TRANSCEND-MCL
Palomba et al. ASTCT 2024
TP53 checked
54/88=61%
32
�Liso-cel in Rel/Ref MCL: TRANSCEND-MCL
Wang et al. JCO 2024
33
�A Smarter Bomb?
Wang NEJM 2020; Wang et al. JCO 2024; van Meerten et al. ASH 2024 Abs 748
| Brexu-cel N=74 | Liso-cel N=83 |
ORR | 93% | 83% |
CR | 67% (73%) | 72% |
Median PFS | 25m (27 m) | 15m |
Median OS | 47m (27 m) | 18m |
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A Smarter Bomb?
Wang NEJM 2020; Wang et al. JCO 2024
| Brexu-cel | Liso-cel |
CRS (All Grade) | 91% | 61% |
| 15% | 1% |
ICANS (All Grade) | 63% | 31% |
| 31% | 9% |
ZUMA-1 (Cohort 6)🡪ZUMA-24 (LBCL)--?🡪ZUMA-XY (MCL)--?
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