tisagenlecleucel vs standard of care as second-line

Poster presented at the 2021 ASCO Annual Meeting, held virtually on 4–8 June 2021Presented at the 2021 ASH Annual Meeting, 11-14 December, 2021; Georgia World Congress Center - Atlanta, GA

Tisagenlecleucel vs Standard of Care as Second-Line Therapy of Primary Refractory or Relapsed Aggressive B-Cell Non-Hodgkin Lymphoma: Analysis of the Phase III BELINDA Study

1

Michael R. Bishop,1 Michael Dickinson2, Duncan Purtill3, Pere Barba4, Armando Santoro5, Nada Hamad6, Koji Kato7, AnnaSureda8, Richard Greil9, Catherine Thieblemont10, Franck Morschhauser11, Martin Janz12, Ian Flinn13, Werner Rabitsch14, YokLam Kwong15, Marie José Kersten16, Monique C. Minnema17, Harald Holte18, Esther Hian Li Chan19, Joaquin Martinez-Lopez20,Antonia M.S. Mueller21, Richard T. Maziarz22, Joseph P. McGuirk23, Emmanuel Bachy24, Steven Le Gouill25,#, Martin Dreyling26,Hideo Harigae27, David Bond28, Charalambos Andreadis29, Peter McSweeney13, Mohamed Kharfan-Dabaja30, SimonNewsome31, Evgeny Degtyarev31, Christopher del Corral32, Giovanna Andreola31, Aisha Masood32, Stephen J. Schuster33, UlrichJaeger34, Peter Borchmann35,*, Jason R. Westin36,*

1The David and Etta Jonas Center for Cellular Therapy, University of Chicago, Chicago, IL, USA; 2Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australia; 3FionaStanley Hospital, Murdoch, WA, Australia; 4Hospital Universitari Vall d’Hebron and Universitat Autonoma de Barcelona, Barcelona, Spain; 5Department of Biomedical Sciences, Humanitas University andIRCCS Humanitas Research Hospital-Humanitas Cancer Center, Milan, Italy; 6Department of Haematology, St Vincent's Hospital Sydney, Australia and St Vincent's Clinical School, Sydney, University ofNew South Wales, Australia; 7Hematology, Oncology, and Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan; 8Clinical Hematology Department, Institut Català d’Oncologia –Hospitalet de Llobregat, Barcelona, Spain; 9Third Medical Department, Paracelsus Medical University; Salzburg Cancer Research Institute-CCCIT and Cancer Cluster Salzburg, Salzburg, Austria;10APHP, Hemato-Oncology, Hôpital Saint-Louis, Paris, France; 11Centre Hospitalier Régional Universitaire de Lille, Lille, France; 12Hematology, Oncology and Tumorimmunology, Charité, UniversityHospital Berlin, Campus Benjamin Franklin, Berlin, Germany; 13Sarah Cannon Research Institute-Tennessee Oncology, Nashville, TN, USA; 14Internal Medicine I, BMT-Unit, Vienna General Hospital-Medical University of Vienna, Vienna, Austria; 15Department of Medicine, Queen Mary Hospital, Hong Kong, China; 18Department of Oncology, Oslo University Hospital, Oslo, Norway and KG JebsenCenter for B-cell Malignancies, Oslo, Norway; 19National University Cancer Institute Singapore, Singapore; 20Hematology Department, Hospital 12 De Octubre, Complutense University, i+12, CNIO,Madrid, Spain; 21Department of Medical Oncology and Hematology, University Hospital, Zurich, Switzerland; 22Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health and ScienceUniversity, Portland, OR, USA; 23Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas Cancer Center, Westwood, KS, USA; 24Hospices Civils de Lyon and UniversitéClaude Bernard Lyon 1, Lyon, France; 25CRCINA, INSERM and Nantes Medical University, Nantes, France; 26Medizinische Klinik III, LMU Klinikum, Munich, Germany; 27Tohoku University Hospital,Sendai, Japan; 28The Ohio State University, Columbus, OH, USA; 29Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA; 30Division ofHematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program, Mayo Clinic, Jacksonville, FL, USA; 31Novartis Pharma AG, Basel, Switzerland; 32Novartis PharmaceuticalsCorporation, East Hanover, NJ, USA; 33Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; 34Clinical Division of Hematology and Hemostaseology,Department of Medicine I, Vienna General Hospital – Medical University of Vienna, Vienna, Austria; 35Clinic I for Internal Medicine, University Hospital Cologne, Cologne, Germany; 36Department ofLymphoma & Myeloma, M.D. Anderson Cancer Center, Houston, TX, USA. *Dr. Borchmann and Dr. Westin are co-senior authors. #At the time of the present work, now affiliated with Institut Curie, Paris,France*Dr. Borchmann and Dr. Westin are co-senior authors. #At the time of the present work, now affiliated with Institut Curie, Paris, France.

LBA #6Michael R. Bishop, MD

[email protected]

Presented at the 2021 ASH Annual Meeting, 11-14 December, 2021; Georgia World Congress Center – Atlanta, GA

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Disclosures

2

MRB declares honoraria from Novartis, Kite-Gilead, AGIOS, Incyte, BMS, Sana Biotechnology, Therakos, Iovance Biotherapeutics; speakers bureau for Kite-Gilead, AGIOS, Incyte, BMS; membership on an entity’s board of directors or

advisory committees for Novartis, Kite-Gilead, CRISPR Therapeutics, BMS, Autolus Ltd, Sana Biotechnology, Therakos, Iovance Biotherapeutics. M. Dickinson declares research funding from Novartis, Roche, Takeda, Celgene, MSD;

consulting fees from Novartis, Bristol-Myers Squibb, Gilead Sciences, Roche, Janssen; honoraria from Roche, Amgen, MSD, Janssen, Bristol-Myers Squibb, Novartis; speakers bureau for Novartis; travel/accommodation/expenses from

Roche. DP declares honoraria (paid directly to institution) from Novartis, Gilead, Jazz, BMS, MSD. PB declares honoraria from Amgen, BMS, Gilead, Novartis, Pfizer. A. Santoro reports membership on an advisory board for BMS, Servier,

Gilead, Pfizer, Eisai, Bayer, MSD; consulting fees for Arqule, Sanofi, Incyte; speakers bureau for Takeda, BMS, Roche, AbbVie, Amgen, Celgene, Servier, Gilead, AstraZeneca, Pfizer, Arqule, Lilly, Sandoz, Eisai, Novartis, Bayer, MSD. NH

declares honoraria for advisory boards for Novartis. KK declares research funding from AbbVie, BMS, Celgene, Chugai, Daiichi Sankyo, Eisai, Janssen, Kyowa Kirin, Ono, Novartis, Takeda; advisory/consultancy fees from AbbVie,

AstraZeneca, Celgene, Chugai, Daiichi Sankyo, Eisai, Janssen, Kyowa Kirin, Novartis; honoraria from BMS, Celgene, Chugai, Dainippon-Sumitomo, Janssen, Kyowa Kirin, Merck, Mundi, Novartis, Ono, Sumitomo Dainippon, Takeda. A.

Sureda declares consultancy/expert testimony for and honoraria from Takeda, BMS/Celgene, MSD, Novartis, Gilead/Kite, GSK, Janssen, AstraZeneca, Sanofi; research funding from Takeda, BMS/Celgene; speakers bureau for Takeda.

RG declares current employment with Paracelsus Medical University Salzburg; consultancy/expert testimony for and honoraria from Celgene, Novartis, Roche, BMS, Takeda, AbbVie, AstraZeneca, Janssen, MSD, Merck, Gilead, Daiichi

Sankyo, Sanofi, Amgen; support for meeting needs and travel from Celgene, Novartis, Roche, BMS, Takeda, AstraZeneca, Janssen, MSD, Gilead, Daiichi Sankyo, Amgen. CT declares research funding from Roche; and honoraria from

and membership on an entity’s board of directors or advisory committees for Roche, AbbVie, Novartis, Gilead, Kite, Incyte, Janssen, Bristol-Myers Squibb/Celgene, Takeda. FM declares consultancy/expert testimony for Roche, Gilead,

Novartis; membership on an entity’s board of directors or advisory committees for Roche, Epizyme, AstraZeneca, Bristol-Myers Squibb, Genmab, AbbVie. MJ declares honoraria from Novartis, Janssen, Takeda, Roche; meeting fees from

Janssen, Takeda, Gilead; travel, accommodations, expenses, meeting fees from Takeda, Gilead. IF reports consultancy/expert testimony for AbbVie, AstraZeneca, BeiGene, Century Therapeutics, Genentech, Genmab, Gilead Sciences,

Great Point Partners, Hutchison MediPharma, Iksuda Therapeutics, InnoCare Pharma, Janssen, Juno Therapeutics, Kite Pharma, MorphoSys, Novartis, Nurix Therapeutics, Pharmacyclics, Roche, Seattle Genetics, Servier

Pharmaceuticals, Takeda, TG Therapeutics, Unum Therapeutics, Verastem, Vincerx Pharma, Yingli Pharmaceuticals; research funding from AbbVie, AstraZeneca, BeiGene, Genentech, Gilead Sciences, Janssen, Juno Therapeutics, Kite

Pharma, MorphoSys, Novartis, Pharmacyclics, Roche, Seattle Genetics, Takeda, TG Therapeutics, Unum Therapeutics, Verastem, Acerta Pharma, Agios, ArQule, Calithera Biosciences, Celgene, Constellation Pharmaceuticals, Curis,

Forma Therapeutics, Forty Seven, IGM Biosciences, Incyte, Infinity Pharmaceuticals, Karyopharm Therapeutics, Loxo, Merck, Pfizer, Portola Pharmaceuticals, Rhizen Pharmaceuticals, Teva, Trillium Therapeutics, Triphase Research &

Development Corp. WR has nothing to declare. YLK declares consultancy/expert testimony for, and research funding and honoraria from Novartis. MJK declares research funding from Kite; honoraria from Kite, Novartis, Miltenyi Biotec,

Celgene/BMS, Takeda; travel reimbursement from Kite, Novartis, Miltenyi Biotec, Celgene/BMS. MCM declares speakers bureau for BMS and consultancy for Janssen-Cilag. H. Holte declares consultancy/expert testimony for Novartis,

Gilead, Nordic Nanovector, Incyte, Genmab; honoraria from Novartis, Gilead, Takeda, Nordic Nanovector, Incyte, Genmab; membership on an entity’s board of directors or advisory committees for Novartis, Takeda, Incyte. EHLC declares

honoraria from Novartis. JML declares consultancy/expert testimony for, honoraria from, and speakers bureau for Novartis, Janssen, BMS, Astellas, Roche, VIVIA Biotech, Sanofi, Karyopharm; research funding from BMS, Astellas, Roche;

membership on an entity’s board of directors or advisory committees for VIVIA Biotech. AMSM declares consultancy/expert testimony for Novartis; honoraria from Novartis, Kite/Gilead, Celgene/BMS, Janssen. RTM declares research

support from Juno, Novartis; consulting fees from AlloVir, Artiva, CRISPR Therapeutics, CytoDyn, Incyte, Novartis; honoraria from Bristol-Myers Squibb/Celgene, Incyte, Intellia, Kite, Omeros, Orca Biosystems, PACT Pharma; patent with

Athersys; participation on a data safety monitoring board for Athersys, Novartis. JPM declares employment with University of Kansas Medical Center; consultancy/expert testimony for Kite, Bristol-Myers Squibb, Novartis, AlloVir, Magenta

Therapeutics, Eco R1 Capital; research funding from Kite, Bristol-Myers Squibb, Novartis, AlloVir. EB declares consultancy/expert testimony for Roche, Takeda, Incyte; research funding from Daiichi; honoraria from Kite/Gilead/Novartis.

SLG has nothing to disclose. M. Dreyling declares research funding from Celgene, Janssen-Cilag, Roche Pharma AG, AbbVie; consulting fees from Acerta Pharma/AstraZeneca, Bayer/Vital, Celgene/Jazz, Gilead Sciences, Janssen-

Cilag, Novartis, Roche, BeiGene; speakers bureau for Bayer Health, Celgene, Gilead Sciences, Janssen-Cilag, Roche Pharma AG; travel/accommodation/expenses from Celgene, Janssen-Cilag, Roche Pharma AG. H. Harigae declares

research funding from Chugai, Kyowa Kirin, Eisai, Takeda, Asahikasei Pharma; honoraria from Novartis, Chugai, Sanofi, Bristol-Myers Squibb. DB declares honoraria from SeaGen and Kite/Gilead. CA declares research funding from

Novartis, GlaxoSmithKline, Amgen, Juno Therapeutics, Celgene, Merck; consulting fees from Gilead Sciences, Kite Pharma, Karyopharm Therapeutics, Atara Biotherapeutics, Incyte, TG Therapeutics, Epizyme;

travel/accommodation/expenses from Gilead Sciences, Kite Pharma. PM declares consultancy/expert testimony for and honoraria from Kite-Gilead, Gamida, TG Therapeutics; research funding from Kite-Gilead, Autolus Limited, Novartis,

NKARTA, AlloVir; speakers bureau for Kite-Gilead. MK-D has nothing to declare. SN reports employment with Novartis. ED reports employment and current equity holder with Novartis. CdC has nothing to declare. GA declares

employment with and current holder of stock options from Novartis. AM declares employment with Novartis. SJS declares research support from AbbVie, Acerta, Celgene/Juno, DTRM Bio, Genentech, Incyte, Merck, Novartis, Portola, TG

Therapeutics; advisory/consultancy fees from Acerta, Allogene, AstraZeneca, BeiGene, Celgene/Juno, Genentech/Roche, LoxoOncology, Novartis, Tessa Therapeutics; honoraria from Acerta, AlloGene, AstraZeneca, BeiGene, Celgene,

Genentech/Roche, LoxoOncology, Novartis, Nordic Nanovector, Pfizer, Tessa Therapeutics; patent from Novartis; steering committee participation for AbbVie, Celgene, Novartis, Juno, Nordic Nanovector, Pfizer; personal fees from

Novartis. UJ declares consulting fees from Novartis, Janssen, Roche; honoraria from Novartis, Janssen, Roche, Gilead, BMS/Celgene, Miltenyi. PB has nothing to declare. JRW declares research support from Celgene, Curis, Forty Seven,

Genentech, Janssen, Kite, Novartis, Unum; advisory/consultancy fees from Celgene, Curis, Genentech, Janssen, Juno, Kite, MorphoSys, Novartis.


Introduction

• Patients with aggressive NHLs relapsed or refractory (r/r) within 12 months of first-line treatment have very

poor prognosis1

• Standard of care (SOC) second-line treatment includes platinum-based immunochemotherapy (PCT),

followed by high-dose chemotherapy and autologous hematopoietic cell transplantation (aHCT) in

responsive patients. However, more than half of patients will not receive aHCT due to inadequate

response2-4

• Tisagenlecleucel is an autologous anti-CD19 CAR T-cell therapy approved for the treatment of r/r DLBCL

after ≥2 lines of treatment5,6

• BELINDA is a global, Phase III, randomized trial comparing the efficacy and safety of the

tisagenlecleucel treatment strategy to the current second-line SOC treatment strategy in

patients with r/r aggressive NHL within 12 months of first-line therapy

3

aHCT, autologous hematopoietic cell transplantation; CAR, chimeric antigen receptor; DLBCL, diffuse large B-cell lymphoma; NHL, non-Hodgkin lymphoma; r/r, refractory or relapsed.

1. Costa LJ, et al. Am J Hematol 2017;92:161-70; 2. Van Den Neste E, et al. Bone Marrow Transplant 2016;51:51-7; 3. van Imhoff GW, et al. J Clin Oncol 2017;35:544-51; 4. Crump M, et al. J Clin Oncol

2014;32:3490-6; 5. Maude SL, et al. N Engl J Med 2018;378:439-48; 6. Schuster SJ, et al. N Engl J Med 2019;380:45-56.


4

Key eligibility criteria:

•≥18 years-old

•Histologically-

confirmed aNHL r/r

within 12 mo of first-

line treatment

•aHCT eligible

•ECOG PS 0-1 Secondary Endpoints:

•OS

•ORR: Best overall

response at/after week 12

•Safety

Primary Endpoint: EFS

EFS Event:

•SD/PD by BIRC at/after

week 12 ± 1 week

•Death at any time

Data cutoff: May 6, 2021

Bridging

chemotherapy as

needed

aHCT, autologous hematopoietic cell transplantation; aNHL, aggressive non-Hodgkin lymphoma; APH, leukapheresis; BIRC, blinded independent review committee; CR, complete response; CT, computed

tomography; ECOG PS, Eastern Cooperative Oncology Group performance status; EFS, event-free survival; HDCT, high-dose chemotherapy; IPI, International Prognostic Index; M, manufacturing; ORR,

overall response rate; OS, overall survival; PCT, platinum-based immunochemotherapy; PD, progressive disease; PET, positron emission tomography; PR, partial response; q3mo, every 3 months; q6mo,

every 6 months; R, randomization; SD, stable disease; SOC, standard of care; US, United States.

BELINDA Study Design

Tisagenlecleucel

infusion


Tisagenlecleucel Arm(N=162)

SOC Arm(N=160)

Age ≥65 yr – no. (%) 54 (33.3) 46 (28.8)

Sex, M – no. (%) 103 (63.6) 98 (61.3)

Region – no. (%)

US† 48 (29.6) 47 (29.4)

Race

White 128 (79.0) 128 (80.0)

Asian 20 (12.3) 22 (13.8)

Black or African American 8 (4.9) 3 (1.9)

Other/Unknown 6 (3.7) 7 (4.4)

Ethnicity Hispanic or Latino 12 (7.4) 13 (8.1)

Disease subtypes – no. (%)

DLBCL-NOS 101 (62.3) 112 (70.0)

HGBL with MYC and BCL2 and/or BCL6 32 (19.8) 19 (11.9)

HGBL-NOS 7 (4.3) 8 (5.0)

PMBCL 12 (7.4) 13 (8.1)

FL grade 3B 5 (3.1) 1 (0.6)

Other 5 (3.1) 7 (4.4)

Remission duration – no. (%)

Refractory 107 (66.0) 107 (66.9)

Relapsed <6 mo 30 (18.5) 32 (20.0)

Relapsed 6-12 mo 25 (15.4) 21 (13.1)

ECOG performance status 1 – no. (%) 70 (43.2) 65 (40.6)

IPI ≥2 – no. (%)* 106 (65.4) 92 (57.5)

Stage at time of study entry – no. (%)

I/IE and II/II E/II Bulky 55 (34.0) 62 (38.8)

III and IV 107 (66.0) 98 (61.3)

Median time since initial diagnosis to randomization, median mo (Q1-Q3) 8.4 (6.8-11.1) 8.2 (5.9-11.4)

Median time since most recent relapse/PD to randomization, median mo (Q1-Q3) 1.4 (0.9-2.2) 1.1 (0.8-1.8)

Baseline Demographic and Disease Characteristics

5

*The imbalance in IPI, despite being a stratification factor, is due to incorrect data entry in the IRT system at the time of randomization.†North America was a stratification factor, and all enrolled patients in this group were from the US. Refractory: Patients who did not achieve CR on first-line therapy to current lymphoma. Relapsed: Patients who had CR on first-line therapy to current lymphoma and relapsed prior to the study. DLBCL diffuse large B-cell lymphoma; ECOG, Eastern Cooperative Oncology Group; FL, follicular lymphoma; HGBL, high-grade B-cell lymphoma; IPI, International Prognostic Index; NOS, not otherwise specified; PD, progressive disease; PMBCL, primary mediastinal B-cell lymphoma; SOC, standard of care; US, United States.


aFAS and safety sets used to compare efficacy and safety between the 2 treatment strategies during the safety comparison period, defined as from day of randomization to the earlier of 56 days after last dose of study treatment or start date of new anticancer therapy. bReasons for discontinuation without tisagenlecleucel infusion include physician decision (n=2, 1.2%), PD (n=2, 1.2%), Manufacturing issue (n=1, 0.6%), and patient decision (n=1, 0.6%). cReasons for discontinuation without aHCT include PD (n=76, 47.5%), physician decision (n=14, 8.8%), death (n=7, 4.4%), patient decision (n=2, 1.3%), technical problems (n=2, 1.3%), and protocol deviation (n=1, 0.6%). aHCT, autologous hematopoietic cell transplantation; FAS, full analysis set; PCT, platinum-based immunochemotherapy; SOC, standard of care.

• Median follow-up: 10 months (range, 2.9-23.2)

Patient Flow


None

27 (17%)

1 cycle

58 (36%)

>1 cycle

77 (48%)

Platinum-based Chemotherapy (PCT)

7

Tisagenlecleucel Arm PCT SOC Arm PCT

>1 cycle includes 20 (12%) patients

who received a second PCT regimen

>1 cycle includes 86 (54%) patients

who received a second PCT regimen

>1 cycle

155 (97%)

None

2 (1%)1 cycle

3 (2%)


Time to Tisagenlecleucel Infusion

8

†North America was a stratification factor, and all enrolled patients in this group were from the United States (US).arange, 1-6 days. brange, 1-17 days

†

• Overall time to infusion was 52 days (range, 31-135)


No Difference in EFS Between Treatment Arms

9

aEFS events defined as PD/SD after day 71 or death at any time. bp-value derived from 1-sided stratified log-rank test. cAdjusted for for potential imbalances in patient characteristics with pre-specified covariates of age, sex, race, ECOG performance status, histological subgroup, disease stage, and disease subtype. dStratified adjusted HR accounting for delayed responses in both arms yield HR of 0.84 (95% CI: 0.63, 1.12).BIRC, blinded independent review committee; CI, confidence interval; EFS, event-free survival; HR, hazard ratio; OS, overall survival; PD, progressive disease; SD, stable disease; SOC, standard of care.

• EFSa was not significantly different

between treatment arms

‒ Primary analysis:

Stratified unadjusted HR: 1.07 (95%

CI, 0.82-1.40, pb=0.69)

‒ Supportive analysis:

Stratified adjustedc HR: 0.95 (95%

CI, 0.72-1.25)

‒ 6 patients responded to

tisagenlecleucel infusion, but were

captured as an EFS event due to

SD/PD before or soon after

infusiond

EFS per BIRC in Tisagenlecleucel and SOC Arms

Tisagenlecleucel arm (N=162):

3.0 months (95% CI, 2.9-4.2)

SOC arm (N=160):

3.0 months (95% CI, 3.0-3.5)


EFS by Pre-infusion Response Status and by Disease Diagnosis in Tisagenlecleucel arm

aTime is relative to date of tisagenlecleucel infusion Median time from pre-infusion disease assessment to infusion was 10 days (range, 2-57; Q1-Q3, 8-15). bEFS events defined as PD/SD after day 71 fromrandomization or death at any time.BIRC, blinded independent review committee; CI, confidence interval; CR, complete response; DLBCL NOS, diffuse large B-cell lymphoma not otherwise specified; EFS, event-free survival; HGBL, high-grade B-cell lymphoma; mEFS, modified event-free survival; NE, not estimable; PD, progressive disease; PMBCL, primary mediastinal B-cell lymphoma; PR, partial response; SD, stable disease; SOC,standard of care.

EFS per BIRC by Disease DiagnosisbEFSa per BIRC by Response Status Pre-infusion

PD: 1.2 mo (95% CI, 1.0-1.4)SD: 1.6 mo (95% CI, 1.2-3.5)

PR: 3.5 mo (95% CI, 2.5-4.2)

CR: 9.2 mo (95% CI, 3.0-NE)

Number of patients still at riskTime (months)

PDSDPRCR

Pro

ba

bilit

y (

%)

of

eve

nt

free

0

20

40

60

80

100

0

41504217

1

25373912

2

5152911

3

3152311

4

211139

5

17

107

6

1785

7

1675

8

1553

9

0553

10

0532

11

0201

12

0101

13

0101

14

0101

15

0101

16

0000

17 18

No. of patients still at riskTime (months)

DLBCL NOS

PMBCL

HBGL

Other

Pro

ba

bilit

y (

%)

of

eve

nt

free

0

20

40

60

80

100

0

101

12

39

10

1

101

12

39

10

2

99

12

36

9

3

49

6

12

3

4

40

6

9

2

5

36

3

6

1

6

26

2

3

1

7

15

1

2

1

8

15

1

2

1

9

12

1

2

1

10

10

1

1

1

11

10

1

1

1

12

5

0

0

1

13

0

0

0

1

14

0

0

0

1

15

0

0

0

1

16

0

0

0

1

17

0

0

0

1

18

0

0

0

0

DLBCL-NOS: 3.5 mo (95% CI, 3.0-5.5)

PMBCL: 4.7 mo (95% CI, 2.8-6.0)

HGBL: 2.8 mo (95% CI, 2.6-3.0)Other: 2.9 mo (95% CI, 2.2-4.7)


ORR at week 6 and Best Overall Response

11

aPrior to tisagenlecleucel infusion as per protocol. Week 6 assessment considered as the earliest assessment on or after day 29 and on or before the earliest of day 70 or new anticancer therapy date and per protocol reflected last disease assessment prior to infusion in the tisagenlecleucel arm and disease status after first PCT in the SOC arm. bAfter tisagenlecleucel infusion as per protocol. BOR considers efficacy assessments on or after day 71 and until SD/PD or start of new therapy. Six patients in the tisagenlecleucel arm and 1 patient in the SOC arm responded after initial SD/PD and without starting a new therapy, but were considered nonresponders for ORR as defined per protocol. BIRC, blinded independent review committee; CI, confidence interval; CR, complete response; mBOR, modified best overall response; mORR, modified overall response rate; ORR, overall response rate; PCT, platinum-based immunochemotherapy; PD, progressive disease; PR, partial response; SD, stable disease; SOC, standard of care; UNK, unknown.

Week 6 Assessmenta

(Response to PCT)

Best Overall Response

(at/after Week 12 Assessment)b

Tisagenlecleucel Arm

(N=162)

SOC Arm

(N=160)


(N=162)

SOC Arm

(N=160)

ORR

CR+PR – no. (%)

95% CI

62 (38.3)

(30.8-46.2)

86 (53.8)

(45.7-61.7)

75 (46.3)

(38.4-54.3)

68 (42.5)

(34.7-50.6)

Best Overall Response – no. (%)

CR 18 (11.1) 31 (19.4) 46 (28.4) 44 (27.5)

PR 44 (27.2) 55 (34.4) 29 (17.9) 24 (15.0)

SD 48 (29.6) 46 (28.8) 19 (11.7) 22 (13.8)

PD 42 (25.9) 22 (13.8) 50 (30.9) 46 (28.8)

UNK 10 (6.2) 6 (3.8) 18 (11.1) 24 (15.0)


Safety

• 52 (32.1%) and 45 (28.1%)

patients in tisagenlecleucel

and SOC arms died on study

– 42 (25.9%) and 32 (20.0%)

died from PD, respectively

– 10 (6.2%) and 13 (8.1%)

died from AEs, respectively

12


(N=162)

SOC Arm

(N=160)

All Grades

no. (%)

Grade ≥3

no. (%)

All Grades

no. (%)

Grade ≥3

no. (%)

AEs* 160 (98.8) 136 (84.0) 158 (98.8) 144 (90.0)

Treatment-relateda 152 (93.8) 121 (74.7) 151 (94.4) 137 (85.6)

Serious AEs* 76 (46.9) 58 (35.8) 82 (51.3) 68 (42.5)

Treatment-relateda 61 (37.7) 44 (27.2) 58 (36.3) 50 (31.3)

Hematological Disorders*,c 127 (78.4) 125 (77.2) 142 (88.8) 141 (88.1)

Anemia 80 (49.4) 54 (33.3) 115 (71.9) 92 (57.5)

Thrombocytopenia 59 (36.4) 52 (32.1) 79 (49.4) 76 (47.5)

Neutropenia 67 (41.4) 65 (40.1) 65 (40.6) 63 (39.4)

Febrile neutropenia 21 (13.0) 21 (13.0) 40 (25.0) 40 (25.0)

Infections*,c 63 (38.9) 28 (17.3) 55 (34.4) 24 (15.0)

CRS and NE Post tisagenlecleucel infusion (N=155)

CRSb 95 (58.6) 8 (4.9) NA NA

NEd 16 (10.3) 3 (1.9) NA NA

*During safety comparison period, defined as from day of randomization to the earlier of: 56 days after last dose of study treatment or start date of new anticancer therapy.aRelated to any part of treatment strategy. bPer Lee grading scale. cAEs in >20% of patients in either arm. dMedian time to onset of a NE was 5 days (range, 3-93), and median time to resolution was 9 days (95% CI, 3-14). AEs, adverse events; CI, confidence interval; CRS, cytokine release syndrome; NA, not applicable; NEs, neurological events; PD, progressive disease; SOC, standard of care.

Most

Common


Conclusions

• EFS was not significantly different between tisagenlecleucel and SOC treatment strategies in

patients with second-line r/r aggressive NHLs

• Our findings suggest the importance of preventing PD prior to infusion

− A higher proportion of patients had PD at week 6, prior to CAR T-cell infusion, in the

tisagenlecleucel arm

• Effective bridging prior to CAR T-cell infusion and a shorter time to infusion for this

chemotherapy-refractory patient population could be critical to improve outcome

• Insights from this randomized Phase III study should help guide optimal use of CAR T-cells in

patients with r/r aggressive NHL requiring second-line therapy and design of future CAR-T

trials

13CAR, chimeric antigen receptor; EFS, event-free survival; NHL, non-Hodgkin lymphoma; PD, progressive disease; r/r, refractory or relapsed; SOC, standard of care.


Acknowledgements

• The authors sincerely thank

− The patients and their families

− Study Steering Committee and Independent Review Committee members

− Investigators and Support staff

− Data Monitoring Committee members

• The study was sponsored by Novartis Pharmaceuticals Corporation and approved by the

institutional review board at each participating institution

• All analyses in this presentation were conducted by Novartis

• Medical writing support and editorial assistance was provided by Healthcare Consultancy

Group, LLC, and was funded by Novartis Pharmaceuticals Corporation

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tisagenlecleucel vs standard of care as second-line

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