Poster presented at the 2021 ASCO Annual Meeting, held virtually on 4–8 June 2021 Presented 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 Dickinson 2 , Duncan Purtill 3 , Pere Barba 4 , Armando Santoro 5 , Nada Hamad 6 , Koji Kato 7 , Anna Sureda 8 , Richard Greil 9 , Catherine Thieblemont 10 , Franck Morschhauser 11 , Martin Janz 12 , Ian Flinn 13 , Werner Rabitsch 14 , Yok Lam Kwong 15 , Marie José Kersten 16 , Monique C. Minnema 17 , Harald Holte 18 , Esther Hian Li Chan 19 , Joaquin Martinez-Lopez 20 , Antonia M.S. Mueller 21 , Richard T. Maziarz 22 , Joseph P. McGuirk 23 , Emmanuel Bachy 24 , Steven Le Gouill 25,# , Martin Dreyling 26 , Hideo Harigae 27 , David Bond 28 , Charalambos Andreadis 29 , Peter McSweeney 13 , Mohamed Kharfan-Dabaja 30 , Simon Newsome 31 , Evgeny Degtyarev 31 , Christopher del Corral 32 , Giovanna Andreola 31 , Aisha Masood 32 , Stephen J. Schuster 33 , Ulrich Jaeger 34 , Peter Borchmann 35,* , Jason R. Westin 36,* 1 The David and Etta Jonas Center for Cellular Therapy, University of Chicago, Chicago, IL, USA; 2 Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australia; 3 Fiona Stanley Hospital, Murdoch, WA, Australia; 4 Hospital Universitari Vall d’Hebron and Universitat Autonoma de Barcelona, Barcelona, Spain; 5 Department of Biomedical Sciences, Humanitas University and IRCCS Humanitas Research Hospital-Humanitas Cancer Center, Milan, Italy; 6 Department of Haematology, St Vincent's Hospital Sydney, Australia and St Vincent's Clinical School, Sydney, University of New South Wales, Australia; 7 Hematology, Oncology, and Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan; 8 Clinical Hematology Department, Institut Català d’Oncologia – Hospitalet de Llobregat, Barcelona, Spain; 9 Third Medical Department, Paracelsus Medical University; Salzburg Cancer Research Institute-CCCIT and Cancer Cluster Salzburg, Salzburg, Austria; 10 APHP, Hemato-Oncology, Hôpital Saint-Louis, Paris, France; 11 Centre Hospitalier Régional Universitaire de Lille, Lille, France; 12 Hematology, Oncology and Tumorimmunology, Charité, University Hospital Berlin, Campus Benjamin Franklin, Berlin, Germany; 13 Sarah Cannon Research Institute-Tennessee Oncology, Nashville, TN, USA; 14 Internal Medicine I, BMT-Unit, Vienna General Hospital- Medical University of Vienna, Vienna, Austria; 15 Department of Medicine, Queen Mary Hospital, Hong Kong, China; 18 Department of Oncology, Oslo University Hospital, Oslo, Norway and KG Jebsen Center for B-cell Malignancies, Oslo, Norway; 19 National University Cancer Institute Singapore, Singapore; 20 Hematology Department, Hospital 12 De Octubre, Complutense University, i+12, CNIO, Madrid, Spain; 21 Department of Medical Oncology and Hematology, University Hospital, Zurich, Switzerland; 22 Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA; 23 Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas Cancer Center, Westwood, KS, USA; 24 Hospices Civils de Lyon and Université Claude Bernard Lyon 1, Lyon, France; 25 CRCINA, INSERM and Nantes Medical University, Nantes, France; 26 Medizinische Klinik III, LMU Klinikum, Munich, Germany; 27 Tohoku University Hospital, Sendai, Japan; 28 The Ohio State University, Columbus, OH, USA; 29 Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA; 30 Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program, Mayo Clinic, Jacksonville, FL, USA; 31 Novartis Pharma AG, Basel, Switzerland; 32 Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 33 Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; 34 Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Vienna General Hospital – Medical University of Vienna, Vienna, Austria; 35 Clinic I for Internal Medicine, University Hospital Cologne, Cologne, Germany; 36 Department of Lymphoma & 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 #6 Michael R. Bishop, MD [email protected]Presented at the 2021 ASH Annual Meeting, 11-14 December, 2021; Georgia World Congress Center – Atlanta, GA Copies of this poster obtained through Quick Response (QR) code are for personal use only and may not be reproduced without permission of the authors. https://bit.ly/BishopMR123 Scan to obtain
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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.
Presented at the 2021 ASH Annual Meeting, 11-14 December, 2021; Georgia World Congress Center – Atlanta, GA
Copies of this poster obtained through
Quick Response (QR) code are for personal use only
and may not be reproduced without permission
of the authors.
https://bit.ly/BishopMR123
Scan to obtain
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
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,
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,
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
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
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,
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
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
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.
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
every 6 months; R, randomization; SD, stable disease; SOC, standard of care; US, United States.
BELINDA Study Design
Tisagenlecleucel
infusion
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 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)
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.
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
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
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
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%)
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
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)
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
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)
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
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)
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
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)
Tisagenlecleucel Arm
(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)
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
*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
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
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.
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
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
14
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