Linton, Kim

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The University of Manchester ResearchLong-Term Efficacy and Safety of Zanubrutinib in Patientswith Relapsed/Refractory (R/R) Marginal Zone Lymphoma(MZL): Final Analysis of the Magnolia (BGB-3111-214) TrialDOI:10.1016/S2666-6367(23)00201-4Document VersionFinal published versionLink to publication record in Manchester Research ExplorerCitation for published version (APA):Linton, K. (2023). Long-Term Efficacy and Safety of Zanubrutinib in Patients with Relapsed/Refractory (R/R)Marginal Zone Lymphoma (MZL): Final Analysis of the Magnolia (BGB-3111-214) Trial. Transplantation andCellular Therapy. https://doi.org/10.1016/S2666-6367(23)00201-4Published in:Transplantation and Cellular TherapyCiting this paperPlease note that where the full-text provided on Manchester Research Explorer is the Author Accepted Manuscriptor Proof version this may differ from the final Published version. If citing, it is advised that you check and use thepublisher's definitive version.General rightsCopyright and moral rights for the publications made accessible in the Research Explorer are retained by theauthors and/or other copyright owners and it is a condition of accessing publications that users recognise andabide by the legal requirements associated with these rights.Takedown policyIf you believe that this document breaches copyright please refer to the University of Manchester’s TakedownProcedures [http://man.ac.uk/04Y6Bo] or contact uml.scholarlycommunications@manchester.ac.uk providingrelevant details, so we can investigate your claim.Download date:30. Jan. 2025 Abstracts / Transplant Cell Ther 29 2S (2021) S1–S468 S105131Comparison of Cyclophosphamide Vs Melphalan Combined with TBI for Pediatric ALL: A Single Center ExperienceMaria A Pereda, MD; Brandon Nuechterlein, MPAS; Kristen Miller and Amy Keating, MD, University of Colorado, Aurora, COIntroduction: Total body irradiation (TBI) is considered the gold standard for pediatric acute lymphoblastic leukemia (ALL) hematopoietic stem cell transplant (HSCT). Different cytotoxic agents in combination with TBI have been studied but direct comparisons are lacking. We present the outcomes of a single center cohort comparing TBI + Melphalan (Mel) and TBI + Cyclophosphamide (CY) based regimens.Objective: To compare the outcomes of TBI+MEL vs TBI/CY based preparative regimens.Methods: Consecutive patients transplanted for ALL between July 2009 and December 2018 at Children’s Hospital Colorado were included. Clinical and demographic data were collected. Kaplan-Meier (KM) curves were reported for overall survival (OS), transplant-related mortality (TRM) censored at day 100, leukemia-free survival (LFS) and GVHD/Relapse-free survival (GRFS). Cumulative incidence functions (CIF) were reported for relapse. Log rank tests, two-sample independent t-tests or Chi-square/Fisher’s exact tests were used to compare by treat-ment group.Results: Ninety patients underwent HSCT for ALL. Patient characteristics and outcomes are summarized in Table 1 and 2, respectively. Mean (± standard deviation) age of trans-plant was 11.91±5.53 years. TBI+ Mel regimens were used in 56 patients (62%). No significance differences were observed in PICU admissions, TRM before day 100, or GVHD incidence. While there were no significant differences observed in 5-year OS (71% in CY, and 70% in Mel), LFS, GRFS and relapse (Figure 1), the cause of death differed between groups. Of patients treated with CY regimens, 80% of deaths were from late complications whereas Mel-treated patients died primarily from relapse (59%), p=0.02.Conclusions: For pediatric ALL, Melphalan + TBI provides similar outcomes to traditional Cy + TBI. Given the complica-tions associated with Cy, Mel may be an attractive alternative for those with disease that is well controlled (ie. next genera-tion sequencing MRD negative) or for patients who have higher complication risks.132Long-Term Efficacy and Safety of Zanubrutinib in Patients with Relapsed/Refractory (R/R) Marginal Zone Lymphoma (MZL): Final Analysis of the Magnolia (BGB-3111-214) TrialStephen Opat, MBBS (Hons), FRACP, FRCPA1; Alessandra Tedeschi, MD2; Bei Hu, MD3; Kim M Linton, MD4; Pamela McKay, MD5; Henry Chan, MBChB, FRACP, FRCPA6; Jie Jin, MD7; Mingyuan Sun, MD8; Magdalena Sobieraj-Teague, MD9; Pier Luigi Zinzani, MD, PhD10; Peter Browett, MD11; Xiaoyan Ke, MD12; Craig A. Portell, MD13; Catherine Thieblemont, MD, PhD14; Kirit Ardeshna, MD15; Fontanet Bijou, MD16; Patricia Walker, MBBS, BMedSci, FRACP, FRCPA17; Eliza A. Hawkes18; Shir-Jing Ho, MD19; Keshu Zhou, MD20; Zhiyu Liang21; Jianfeng Xu22; Chris Tankersley22; Richard Delarue22; Melannie Co, MD23 and Judith Trotman, MD24, 1 Monash University, Clayton, VIC, Australia, 2 ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy, Milan, Italy, 3 Levine Cancer Institute, Charlotte, NC, 4 Manchester Cancer Research Centre, Division of Cancer Sciences, Manchester, UK, Manchester, United Kingdom, 5 Beatson West of Scotland Cancer Centre, Glasgow, UK, Glasgow, United Kingdom, 6 North Shore Hospital, Auckland, New Zealand, 7 The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China, Zhejiang, China, 8 Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China, Tianjin, China, 9 Flinders Medical Centre, Bedford Park, SA, Australia, Bedford Park, SA, Australia, 10 Institute of Hematology “Seràgnoli”, University of Bologna, Bologna, Italy, 11 Hematology Unit, Auckland City Hospital, Auckland, New Zealand, 12 Peking University Third Hospital, Beijing, China, Beijing, China, 13 University of Virginia, Comprehensive Cancer Center, Charlottesville, VA, USA, Charlottesville, VA, 14 Paris University; Assistante publique-Hôpitaux de Paris, Hemato-oncology, F-75010, Paris, France, 15 University College London Hospitals, London, UK, London, United Kingdom, 16 Institut Bergonié, Bordeaux, France, Bordeaux, France, 17 Peninsula Private Hospital, Frankston, VIC, Australia, 18 Box Hill Hospital, Box Hill, VIC, Australia, Box Hill, VIC, Australia, 19 St. George Hospital, Kogarah, NSW, Australia, Kogarah, NSW, Australia, 20 Henan Cancer Hospital, Zhengzhou, Henan, China, Henan, China, 21 21BeiGene (Beijing) Co., Ltd., Beijing, China, BeiGene Switzerland GmbH and BeiGene USA, Inc., San Mateo, CA, USA, San Mateo, CA, 22 BeiGene (Beijing) Co., Ltd., Beijing, China, BeiGene Switzerland GmbH and BeiGene USA, Inc., San Mateo, S106 Abstracts / Transplant Cell Ther 29 2S (2021) S1–S468CA, USA, San Mateo, CA, 23 BeiGene (Shanghai) Co., Ltd and BeiGene USA, Inc., San Mateo, CA, 24 Concord Repatriation General Hospital, University of Sydney, Concord, NSW, Australia, Concord, NSW, AustraliaIntroduction: Advanced MZL is generally incurable, with periods of remission and relapse. Zanubrutinib (BGB-3111), a potent and highly specific next-generation Bruton tyrosine kinase (BTK) inhibitor, was approved in the US and Canada for R/R MZL based on the MAGNOLIA primary analysis (BGB-3111-214; NCT03846427); here, the final MAGNOLIA analysis is presented.Methods: This was a phase 2, multicenter, single-arm study of adult patients (pts) with R/R MZL (≥1 prior CD20-directed therapy). Zanubrutinib (160 mg twice daily) was given until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) by independent review committee (IRC) per Lugano classification. Secondary endpoints were investigator-assessed ORR, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Efficacy was assessed by positron emission tomog-raphy (PET)-based Lugano criteria for IRC-confirmed fluorode-oxyglucose (FDG)-avid disease at baseline; non-avid disease was assessed by computed tomography (CT)-based criteria.Results: As of May 4, 2022, 68 pts were treated (median age=70 y [range 37-95]; ≥75 y=27.9%). MZL subtypes included extran-odal (38.2%), nodal (38.2%), splenic (17.6%), and unknown (5.9%). The median number of prior therapies was 2 (range 1-6); 32.4% of pts had disease refractory to last therapy, most (89.7%) had prior chemoimmunotherapy, and 7 (10.3%) had rituximab monotherapy as their only prior treatment. Sixty-one pts (89.7%) had FDG-avid disease. After a median follow-up of 28.0 mos (range 1.6-32.9) and a median treatment duration of 24.2 mos (range 0.9-32.9), 66 pts were effica-cy-evaluable. IRC-assessed ORR (complete response [CR]+partial response [PR]) was 68.2% (CR=25.8%). By subtype, ORR/CR rates were 64.0%/40.0% (extranodal), 76.0%/20.0% (nodal), 66.7%/8.3% (splenic), and 50.0%/25.0% (unknown). Median DOR, PFS, and OS were not reached. Over 70.0% of pts were alive or progression-free after 2 years (Figure). Sensitivity analysis using only CT-based criteria (n=66) showed an ORR of 66.7% and CR of 24.2%. The most common treatment-emergent AEs were bruising (23.5%), diarrhea (22.1%), and constipation (17.6%). Neutropenia (8.8%) and COVID-19 pneumonia (5.9%) were the most common Grade ≥3 AEs. Five pts (7.4%) died due to unrelated AEs: COVID-19 pneumonia=2, acute myeloid leukemia=1, myocardial infarction=1, septic encephalopathy=1. Hypertension occurred in 3 pts (4.4%), atrial fibrillation and atrial flutter in 1 pt (1.5%) each; none led to treatment with-drawal. One pt (1.5%) had a Grade 3 gastrointestinal hemor-rhage while receiving rivaroxaban. None of the pts required dose reduction.Conclusions: In this final analysis with over 2 years of median follow-up, zanubrutinib continues to demonstrate durable disease control and was generally well tolerated, with no new safety signals observed.133Myeloablative Vs Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation in Philadelphia-Chromosome Positive Acute Lymphoblastic LeukemiaTamer Othman1; Paul Koller, MD2; Ni-Chun Tsai, MS, MPH3; Hoda Pourhassan, MD4; Vaibhav Agrawal, MD5; Salman Otoukesh, MD2; Idoroenyi Amanam, MD2; Dat Ngo6; Jason Chen7; Monzr M. Al Malki, MD2; Amandeep Salhotra, MD2; Haris Ali, MD2; Ahmed Aribi, MD8; Karamjeet S. Sandhu, MD2; Shukaib Arslan, MD2; Brian Ball, MD2; Forrest Stewart2; Peter Curtin, MD2; Andrew S. Artz, MD2; David S Snyder8; Guido Marcucci, MD2; Stephen J. Forman, MD2; Anthony S. Stein, MD2; Ryotaro Nakamura, MD9; Vinod Pullarkat, MD2; Ibrahim Aldoss, MD2 and Matthew Mei, MD8, 1 UC Davis Comprehensive Cancer Center, Sacramento, CA, 2 Department of Hematology/HCT, City of Hope National Medical Center, Duarte, CA, 3 Department of Computational and Quantitative Medicine-BRI, City of Hope National Medical Center, Duarte, CA, 4 Hematology and Hematopoietic Transplantation, City of Hope, duarte, CA, 5 Hematology/HCT, City of Hope National Medical Center, Duarte, CA, 6 Department of Pharmancy, City of Hope National Medical Center, Duarte, CA, 7 Department of Pharmacy, City of Hope National Medical Center, Duarte, CA, 8 Hematology/Hematopoietic Cell Transplant, City of Hope National Medical Center, Duarte, CA, 9 Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, Duarte, CABackground: Philadelphia-chromosome positive acute lymph-oblastic leukemia (Ph+ ALL) has historically been associated with a poor prognosis. Allogeneic hematopoietic cell trans-plantation (HCT) is recommended in first complete remission (CR1). Strategies to decrease non-relapse mortality (NRM) and to increase the number of patients eligible to receive HCT have led to the utilization of reduced intensity conditioning (RIC) for patients unfit or too old for myeloablative conditioning (MAC), at the cost of a higher risk of relapse. Limited data exist comparing MAC vs. RIC HCT in Ph+ ALL. Here, we compared the outcomes of MAC- and RIC-HCT in Ph+ ALL.Methods: This was a single-center retrospective study exam-ining patients with Ph+ ALL who underwent HCT from 2000-2019. The primary endpoint was progression free survival (PFS), while secondary endpoints include overall survival (OS), graft versus host disease free survival (GRFS), non-relapse mortality (NRM), and cumulative incidence of relapse (CIR), 

Long-Term Efficacy and Safety of Zanubrutinib in Patients with Relapsed/Refractory (R/R) Marginal Zone Lymphoma (MZL): Final Analysis of the Magnolia (BGB-3111-214) Trial

The University of Manchester ResearchLong-Term Efficacy and Safety of Zanubrutinib in Patientswith Relapsed/Refractory (R/R) Marginal Zone Lymphoma(MZL): Final Analysis of the Magnolia (BGB-3111-214) TrialDOI:10.1016/S2666-6367(23)00201-4Document VersionFinal published versionLink to publication record in Manchester Research ExplorerCitation for published version (APA):Linton, K. (2023). Long-Term Efficacy and Safety of Zanubrutinib in Patients with Relapsed/Refractory (R/R)Marginal Zone Lymphoma (MZL): Final Analysis of the Magnolia (BGB-3111-214) Trial. Transplantation andCellular Therapy. https://doi.org/10.1016/S2666-6367(23)00201-4Published in:Transplantation and Cellular TherapyCiting this paperPlease note that where the full-text provided on Manchester Research Explorer is the Author Accepted Manuscriptor Proof version this may differ from the final Published version. If citing, it is advised that you check and use thepublisher's definitive version.General rightsCopyright and moral rights for the publications made accessible in the Research Explorer are retained by theauthors and/or other copyright owners and it is a condition of accessing publications that users recognise andabide by the legal requirements associated with these rights.Takedown policyIf you believe that this document breaches copyright please refer to the University of Manchester’s TakedownProcedures [http://man.ac.uk/04Y6Bo] or contact openresearch@manchester.ac.uk providing relevant details, sowe can investigate your claim.Download date:26. Dec. 2025 Abstracts / Transplant Cell Ther 29 2S (2021) S1–S468 S105131Comparison of Cyclophosphamide Vs Melphalan Combined with TBI for Pediatric ALL: A Single Center ExperienceMaria A Pereda, MD; Brandon Nuechterlein, MPAS; Kristen Miller and Amy Keating, MD, University of Colorado, Aurora, COIntroduction: Total body irradiation (TBI) is considered the gold standard for pediatric acute lymphoblastic leukemia (ALL) hematopoietic stem cell transplant (HSCT). Different cytotoxic agents in combination with TBI have been studied but direct comparisons are lacking. We present the outcomes of a single center cohort comparing TBI + Melphalan (Mel) and TBI + Cyclophosphamide (CY) based regimens.Objective: To compare the outcomes of TBI+MEL vs TBI/CY based preparative regimens.Methods: Consecutive patients transplanted for ALL between July 2009 and December 2018 at Children’s Hospital Colorado were included. Clinical and demographic data were collected. Kaplan-Meier (KM) curves were reported for overall survival (OS), transplant-related mortality (TRM) censored at day 100, leukemia-free survival (LFS) and GVHD/Relapse-free survival (GRFS). Cumulative incidence functions (CIF) were reported for relapse. Log rank tests, two-sample independent t-tests or Chi-square/Fisher’s exact tests were used to compare by treat-ment group.Results: Ninety patients underwent HSCT for ALL. Patient characteristics and outcomes are summarized in Table 1 and 2, respectively. Mean (± standard deviation) age of trans-plant was 11.91±5.53 years. TBI+ Mel regimens were used in 56 patients (62%). No significance differences were observed in PICU admissions, TRM before day 100, or GVHD incidence. While there were no significant differences observed in 5-year OS (71% in CY, and 70% in Mel), LFS, GRFS and relapse (Figure 1), the cause of death differed between groups. Of patients treated with CY regimens, 80% of deaths were from late complications whereas Mel-treated patients died primarily from relapse (59%), p=0.02.Conclusions: For pediatric ALL, Melphalan + TBI provides similar outcomes to traditional Cy + TBI. Given the complica-tions associated with Cy, Mel may be an attractive alternative for those with disease that is well controlled (ie. next genera-tion sequencing MRD negative) or for patients who have higher complication risks.132Long-Term Efficacy and Safety of Zanubrutinib in Patients with Relapsed/Refractory (R/R) Marginal Zone Lymphoma (MZL): Final Analysis of the Magnolia (BGB-3111-214) TrialStephen Opat, MBBS (Hons), FRACP, FRCPA1; Alessandra Tedeschi, MD2; Bei Hu, MD3; Kim M Linton, MD4; Pamela McKay, MD5; Henry Chan, MBChB, FRACP, FRCPA6; Jie Jin, MD7; Mingyuan Sun, MD8; Magdalena Sobieraj-Teague, MD9; Pier Luigi Zinzani, MD, PhD10; Peter Browett, MD11; Xiaoyan Ke, MD12; Craig A. Portell, MD13; Catherine Thieblemont, MD, PhD14; Kirit Ardeshna, MD15; Fontanet Bijou, MD16; Patricia Walker, MBBS, BMedSci, FRACP, FRCPA17; Eliza A. Hawkes18; Shir-Jing Ho, MD19; Keshu Zhou, MD20; Zhiyu Liang21; Jianfeng Xu22; Chris Tankersley22; Richard Delarue22; Melannie Co, MD23 and Judith Trotman, MD24, 1 Monash University, Clayton, VIC, Australia, 2 ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy, Milan, Italy, 3 Levine Cancer Institute, Charlotte, NC, 4 Manchester Cancer Research Centre, Division of Cancer Sciences, Manchester, UK, Manchester, United Kingdom, 5 Beatson West of Scotland Cancer Centre, Glasgow, UK, Glasgow, United Kingdom, 6 North Shore Hospital, Auckland, New Zealand, 7 The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China, Zhejiang, China, 8 Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China, Tianjin, China, 9 Flinders Medical Centre, Bedford Park, SA, Australia, Bedford Park, SA, Australia, 10 Institute of Hematology “Seràgnoli”, University of Bologna, Bologna, Italy, 11 Hematology Unit, Auckland City Hospital, Auckland, New Zealand, 12 Peking University Third Hospital, Beijing, China, Beijing, China, 13 University of Virginia, Comprehensive Cancer Center, Charlottesville, VA, USA, Charlottesville, VA, 14 Paris University; Assistante publique-Hôpitaux de Paris, Hemato-oncology, F-75010, Paris, France, 15 University College London Hospitals, London, UK, London, United Kingdom, 16 Institut Bergonié, Bordeaux, France, Bordeaux, France, 17 Peninsula Private Hospital, Frankston, VIC, Australia, 18 Box Hill Hospital, Box Hill, VIC, Australia, Box Hill, VIC, Australia, 19 St. George Hospital, Kogarah, NSW, Australia, Kogarah, NSW, Australia, 20 Henan Cancer Hospital, Zhengzhou, Henan, China, Henan, China, 21 21BeiGene (Beijing) Co., Ltd., Beijing, China, BeiGene Switzerland GmbH and BeiGene USA, Inc., San Mateo, CA, USA, San Mateo, CA, 22 BeiGene (Beijing) Co., Ltd., Beijing, China, BeiGene Switzerland GmbH and BeiGene USA, Inc., San Mateo, S106 Abstracts / Transplant Cell Ther 29 2S (2021) S1–S468CA, USA, San Mateo, CA, 23 BeiGene (Shanghai) Co., Ltd and BeiGene USA, Inc., San Mateo, CA, 24 Concord Repatriation General Hospital, University of Sydney, Concord, NSW, Australia, Concord, NSW, AustraliaIntroduction: Advanced MZL is generally incurable, with periods of remission and relapse. Zanubrutinib (BGB-3111), a potent and highly specific next-generation Bruton tyrosine kinase (BTK) inhibitor, was approved in the US and Canada for R/R MZL based on the MAGNOLIA primary analysis (BGB-3111-214; NCT03846427); here, the final MAGNOLIA analysis is presented.Methods: This was a phase 2, multicenter, single-arm study of adult patients (pts) with R/R MZL (≥1 prior CD20-directed therapy). Zanubrutinib (160 mg twice daily) was given until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) by independent review committee (IRC) per Lugano classification. Secondary endpoints were investigator-assessed ORR, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Efficacy was assessed by positron emission tomog-raphy (PET)-based Lugano criteria for IRC-confirmed fluorode-oxyglucose (FDG)-avid disease at baseline; non-avid disease was assessed by computed tomography (CT)-based criteria.Results: As of May 4, 2022, 68 pts were treated (median age=70 y [range 37-95]; ≥75 y=27.9%). MZL subtypes included extran-odal (38.2%), nodal (38.2%), splenic (17.6%), and unknown (5.9%). The median number of prior therapies was 2 (range 1-6); 32.4% of pts had disease refractory to last therapy, most (89.7%) had prior chemoimmunotherapy, and 7 (10.3%) had rituximab monotherapy as their only prior treatment. Sixty-one pts (89.7%) had FDG-avid disease. After a median follow-up of 28.0 mos (range 1.6-32.9) and a median treatment duration of 24.2 mos (range 0.9-32.9), 66 pts were effica-cy-evaluable. IRC-assessed ORR (complete response [CR]+partial response [PR]) was 68.2% (CR=25.8%). By subtype, ORR/CR rates were 64.0%/40.0% (extranodal), 76.0%/20.0% (nodal), 66.7%/8.3% (splenic), and 50.0%/25.0% (unknown). Median DOR, PFS, and OS were not reached. Over 70.0% of pts were alive or progression-free after 2 years (Figure). Sensitivity analysis using only CT-based criteria (n=66) showed an ORR of 66.7% and CR of 24.2%. The most common treatment-emergent AEs were bruising (23.5%), diarrhea (22.1%), and constipation (17.6%). Neutropenia (8.8%) and COVID-19 pneumonia (5.9%) were the most common Grade ≥3 AEs. Five pts (7.4%) died due to unrelated AEs: COVID-19 pneumonia=2, acute myeloid leukemia=1, myocardial infarction=1, septic encephalopathy=1. Hypertension occurred in 3 pts (4.4%), atrial fibrillation and atrial flutter in 1 pt (1.5%) each; none led to treatment with-drawal. One pt (1.5%) had a Grade 3 gastrointestinal hemor-rhage while receiving rivaroxaban. None of the pts required dose reduction.Conclusions: In this final analysis with over 2 years of median follow-up, zanubrutinib continues to demonstrate durable disease control and was generally well tolerated, with no new safety signals observed.133Myeloablative Vs Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation in Philadelphia-Chromosome Positive Acute Lymphoblastic LeukemiaTamer Othman1; Paul Koller, MD2; Ni-Chun Tsai, MS, MPH3; Hoda Pourhassan, MD4; Vaibhav Agrawal, MD5; Salman Otoukesh, MD2; Idoroenyi Amanam, MD2; Dat Ngo6; Jason Chen7; Monzr M. Al Malki, MD2; Amandeep Salhotra, MD2; Haris Ali, MD2; Ahmed Aribi, MD8; Karamjeet S. Sandhu, MD2; Shukaib Arslan, MD2; Brian Ball, MD2; Forrest Stewart2; Peter Curtin, MD2; Andrew S. Artz, MD2; David S Snyder8; Guido Marcucci, MD2; Stephen J. Forman, MD2; Anthony S. Stein, MD2; Ryotaro Nakamura, MD9; Vinod Pullarkat, MD2; Ibrahim Aldoss, MD2 and Matthew Mei, MD8, 1 UC Davis Comprehensive Cancer Center, Sacramento, CA, 2 Department of Hematology/HCT, City of Hope National Medical Center, Duarte, CA, 3 Department of Computational and Quantitative Medicine-BRI, City of Hope National Medical Center, Duarte, CA, 4 Hematology and Hematopoietic Transplantation, City of Hope, duarte, CA, 5 Hematology/HCT, City of Hope National Medical Center, Duarte, CA, 6 Department of Pharmancy, City of Hope National Medical Center, Duarte, CA, 7 Department of Pharmacy, City of Hope National Medical Center, Duarte, CA, 8 Hematology/Hematopoietic Cell Transplant, City of Hope National Medical Center, Duarte, CA, 9 Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, Duarte, CABackground: Philadelphia-chromosome positive acute lymph-oblastic leukemia (Ph+ ALL) has historically been associated with a poor prognosis. Allogeneic hematopoietic cell trans-plantation (HCT) is recommended in first complete remission (CR1). Strategies to decrease non-relapse mortality (NRM) and to increase the number of patients eligible to receive HCT have led to the utilization of reduced intensity conditioning (RIC) for patients unfit or too old for myeloablative conditioning (MAC), at the cost of a higher risk of relapse. Limited data exist comparing MAC vs. RIC HCT in Ph+ ALL. Here, we compared the outcomes of MAC- and RIC-HCT in Ph+ ALL.Methods: This was a single-center retrospective study exam-ining patients with Ph+ ALL who underwent HCT from 2000-2019. The primary endpoint was progression free survival (PFS), while secondary endpoints include overall survival (OS), graft versus host disease free survival (GRFS), non-relapse mortality (NRM), and cumulative incidence of relapse (CIR), 

The University of Manchester ResearchLong-Term Efficacy and Safety of Zanubrutinib in Patientswith Relapsed/Refractory (R/R) Marginal Zone Lymphoma(MZL): Final Analysis of the Magnolia (BGB-3111-214) TrialDOI:10.1016/S2666-6367(23)00201-4Document VersionFinal published versionLink to publication record in Manchester Research ExplorerCitation for published version (APA):Linton, K. (2023). Long-Term Efficacy and Safety of Zanubrutinib in Patients with Relapsed/Refractory (R/R)Marginal Zone Lymphoma (MZL): Final Analysis of the Magnolia (BGB-3111-214) Trial. Transplantation andCellular Therapy. https://doi.org/10.1016/S2666-6367(23)00201-4Published in:Transplantation and Cellular TherapyCiting this paperPlease note that where the full-text provided on Manchester Research Explorer is the Author Accepted Manuscriptor Proof version this may differ from the final Published version. If citing, it is advised that you check and use thepublisher's definitive version.General rightsCopyright and moral rights for the publications made accessible in the Research Explorer are retained by theauthors and/or other copyright owners and it is a condition of accessing publications that users recognise andabide by the legal requirements associated with these rights.Takedown policyIf you believe that this document breaches copyright please refer to the University of Manchester’s TakedownProcedures [http://man.ac.uk/04Y6Bo] or contact openresearch@manchester.ac.uk providing relevant details, sowe can investigate your claim.Download date:15. Oct. 2025 Abstracts / Transplant Cell Ther 29 2S (2021) S1–S468 S105131Comparison of Cyclophosphamide Vs Melphalan Combined with TBI for Pediatric ALL: A Single Center ExperienceMaria A Pereda, MD; Brandon Nuechterlein, MPAS; Kristen Miller and Amy Keating, MD, University of Colorado, Aurora, COIntroduction: Total body irradiation (TBI) is considered the gold standard for pediatric acute lymphoblastic leukemia (ALL) hematopoietic stem cell transplant (HSCT). Different cytotoxic agents in combination with TBI have been studied but direct comparisons are lacking. We present the outcomes of a single center cohort comparing TBI + Melphalan (Mel) and TBI + Cyclophosphamide (CY) based regimens.Objective: To compare the outcomes of TBI+MEL vs TBI/CY based preparative regimens.Methods: Consecutive patients transplanted for ALL between July 2009 and December 2018 at Children’s Hospital Colorado were included. Clinical and demographic data were collected. Kaplan-Meier (KM) curves were reported for overall survival (OS), transplant-related mortality (TRM) censored at day 100, leukemia-free survival (LFS) and GVHD/Relapse-free survival (GRFS). Cumulative incidence functions (CIF) were reported for relapse. Log rank tests, two-sample independent t-tests or Chi-square/Fisher’s exact tests were used to compare by treat-ment group.Results: Ninety patients underwent HSCT for ALL. Patient characteristics and outcomes are summarized in Table 1 and 2, respectively. Mean (± standard deviation) age of trans-plant was 11.91±5.53 years. TBI+ Mel regimens were used in 56 patients (62%). No significance differences were observed in PICU admissions, TRM before day 100, or GVHD incidence. While there were no significant differences observed in 5-year OS (71% in CY, and 70% in Mel), LFS, GRFS and relapse (Figure 1), the cause of death differed between groups. Of patients treated with CY regimens, 80% of deaths were from late complications whereas Mel-treated patients died primarily from relapse (59%), p=0.02.Conclusions: For pediatric ALL, Melphalan + TBI provides similar outcomes to traditional Cy + TBI. Given the complica-tions associated with Cy, Mel may be an attractive alternative for those with disease that is well controlled (ie. next genera-tion sequencing MRD negative) or for patients who have higher complication risks.132Long-Term Efficacy and Safety of Zanubrutinib in Patients with Relapsed/Refractory (R/R) Marginal Zone Lymphoma (MZL): Final Analysis of the Magnolia (BGB-3111-214) TrialStephen Opat, MBBS (Hons), FRACP, FRCPA1; Alessandra Tedeschi, MD2; Bei Hu, MD3; Kim M Linton, MD4; Pamela McKay, MD5; Henry Chan, MBChB, FRACP, FRCPA6; Jie Jin, MD7; Mingyuan Sun, MD8; Magdalena Sobieraj-Teague, MD9; Pier Luigi Zinzani, MD, PhD10; Peter Browett, MD11; Xiaoyan Ke, MD12; Craig A. Portell, MD13; Catherine Thieblemont, MD, PhD14; Kirit Ardeshna, MD15; Fontanet Bijou, MD16; Patricia Walker, MBBS, BMedSci, FRACP, FRCPA17; Eliza A. Hawkes18; Shir-Jing Ho, MD19; Keshu Zhou, MD20; Zhiyu Liang21; Jianfeng Xu22; Chris Tankersley22; Richard Delarue22; Melannie Co, MD23 and Judith Trotman, MD24, 1 Monash University, Clayton, VIC, Australia, 2 ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy, Milan, Italy, 3 Levine Cancer Institute, Charlotte, NC, 4 Manchester Cancer Research Centre, Division of Cancer Sciences, Manchester, UK, Manchester, United Kingdom, 5 Beatson West of Scotland Cancer Centre, Glasgow, UK, Glasgow, United Kingdom, 6 North Shore Hospital, Auckland, New Zealand, 7 The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China, Zhejiang, China, 8 Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China, Tianjin, China, 9 Flinders Medical Centre, Bedford Park, SA, Australia, Bedford Park, SA, Australia, 10 Institute of Hematology “Seràgnoli”, University of Bologna, Bologna, Italy, 11 Hematology Unit, Auckland City Hospital, Auckland, New Zealand, 12 Peking University Third Hospital, Beijing, China, Beijing, China, 13 University of Virginia, Comprehensive Cancer Center, Charlottesville, VA, USA, Charlottesville, VA, 14 Paris University; Assistante publique-Hôpitaux de Paris, Hemato-oncology, F-75010, Paris, France, 15 University College London Hospitals, London, UK, London, United Kingdom, 16 Institut Bergonié, Bordeaux, France, Bordeaux, France, 17 Peninsula Private Hospital, Frankston, VIC, Australia, 18 Box Hill Hospital, Box Hill, VIC, Australia, Box Hill, VIC, Australia, 19 St. George Hospital, Kogarah, NSW, Australia, Kogarah, NSW, Australia, 20 Henan Cancer Hospital, Zhengzhou, Henan, China, Henan, China, 21 21BeiGene (Beijing) Co., Ltd., Beijing, China, BeiGene Switzerland GmbH and BeiGene USA, Inc., San Mateo, CA, USA, San Mateo, CA, 22 BeiGene (Beijing) Co., Ltd., Beijing, China, BeiGene Switzerland GmbH and BeiGene USA, Inc., San Mateo, S106 Abstracts / Transplant Cell Ther 29 2S (2021) S1–S468CA, USA, San Mateo, CA, 23 BeiGene (Shanghai) Co., Ltd and BeiGene USA, Inc., San Mateo, CA, 24 Concord Repatriation General Hospital, University of Sydney, Concord, NSW, Australia, Concord, NSW, AustraliaIntroduction: Advanced MZL is generally incurable, with periods of remission and relapse. Zanubrutinib (BGB-3111), a potent and highly specific next-generation Bruton tyrosine kinase (BTK) inhibitor, was approved in the US and Canada for R/R MZL based on the MAGNOLIA primary analysis (BGB-3111-214; NCT03846427); here, the final MAGNOLIA analysis is presented.Methods: This was a phase 2, multicenter, single-arm study of adult patients (pts) with R/R MZL (≥1 prior CD20-directed therapy). Zanubrutinib (160 mg twice daily) was given until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) by independent review committee (IRC) per Lugano classification. Secondary endpoints were investigator-assessed ORR, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Efficacy was assessed by positron emission tomog-raphy (PET)-based Lugano criteria for IRC-confirmed fluorode-oxyglucose (FDG)-avid disease at baseline; non-avid disease was assessed by computed tomography (CT)-based criteria.Results: As of May 4, 2022, 68 pts were treated (median age=70 y [range 37-95]; ≥75 y=27.9%). MZL subtypes included extran-odal (38.2%), nodal (38.2%), splenic (17.6%), and unknown (5.9%). The median number of prior therapies was 2 (range 1-6); 32.4% of pts had disease refractory to last therapy, most (89.7%) had prior chemoimmunotherapy, and 7 (10.3%) had rituximab monotherapy as their only prior treatment. Sixty-one pts (89.7%) had FDG-avid disease. After a median follow-up of 28.0 mos (range 1.6-32.9) and a median treatment duration of 24.2 mos (range 0.9-32.9), 66 pts were effica-cy-evaluable. IRC-assessed ORR (complete response [CR]+partial response [PR]) was 68.2% (CR=25.8%). By subtype, ORR/CR rates were 64.0%/40.0% (extranodal), 76.0%/20.0% (nodal), 66.7%/8.3% (splenic), and 50.0%/25.0% (unknown). Median DOR, PFS, and OS were not reached. Over 70.0% of pts were alive or progression-free after 2 years (Figure). Sensitivity analysis using only CT-based criteria (n=66) showed an ORR of 66.7% and CR of 24.2%. The most common treatment-emergent AEs were bruising (23.5%), diarrhea (22.1%), and constipation (17.6%). Neutropenia (8.8%) and COVID-19 pneumonia (5.9%) were the most common Grade ≥3 AEs. Five pts (7.4%) died due to unrelated AEs: COVID-19 pneumonia=2, acute myeloid leukemia=1, myocardial infarction=1, septic encephalopathy=1. Hypertension occurred in 3 pts (4.4%), atrial fibrillation and atrial flutter in 1 pt (1.5%) each; none led to treatment with-drawal. One pt (1.5%) had a Grade 3 gastrointestinal hemor-rhage while receiving rivaroxaban. None of the pts required dose reduction.Conclusions: In this final analysis with over 2 years of median follow-up, zanubrutinib continues to demonstrate durable disease control and was generally well tolerated, with no new safety signals observed.133Myeloablative Vs Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation in Philadelphia-Chromosome Positive Acute Lymphoblastic LeukemiaTamer Othman1; Paul Koller, MD2; Ni-Chun Tsai, MS, MPH3; Hoda Pourhassan, MD4; Vaibhav Agrawal, MD5; Salman Otoukesh, MD2; Idoroenyi Amanam, MD2; Dat Ngo6; Jason Chen7; Monzr M. Al Malki, MD2; Amandeep Salhotra, MD2; Haris Ali, MD2; Ahmed Aribi, MD8; Karamjeet S. Sandhu, MD2; Shukaib Arslan, MD2; Brian Ball, MD2; Forrest Stewart2; Peter Curtin, MD2; Andrew S. Artz, MD2; David S Snyder8; Guido Marcucci, MD2; Stephen J. Forman, MD2; Anthony S. Stein, MD2; Ryotaro Nakamura, MD9; Vinod Pullarkat, MD2; Ibrahim Aldoss, MD2 and Matthew Mei, MD8, 1 UC Davis Comprehensive Cancer Center, Sacramento, CA, 2 Department of Hematology/HCT, City of Hope National Medical Center, Duarte, CA, 3 Department of Computational and Quantitative Medicine-BRI, City of Hope National Medical Center, Duarte, CA, 4 Hematology and Hematopoietic Transplantation, City of Hope, duarte, CA, 5 Hematology/HCT, City of Hope National Medical Center, Duarte, CA, 6 Department of Pharmancy, City of Hope National Medical Center, Duarte, CA, 7 Department of Pharmacy, City of Hope National Medical Center, Duarte, CA, 8 Hematology/Hematopoietic Cell Transplant, City of Hope National Medical Center, Duarte, CA, 9 Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, Duarte, CABackground: Philadelphia-chromosome positive acute lymph-oblastic leukemia (Ph+ ALL) has historically been associated with a poor prognosis. Allogeneic hematopoietic cell trans-plantation (HCT) is recommended in first complete remission (CR1). Strategies to decrease non-relapse mortality (NRM) and to increase the number of patients eligible to receive HCT have led to the utilization of reduced intensity conditioning (RIC) for patients unfit or too old for myeloablative conditioning (MAC), at the cost of a higher risk of relapse. Limited data exist comparing MAC vs. RIC HCT in Ph+ ALL. Here, we compared the outcomes of MAC- and RIC-HCT in Ph+ ALL.Methods: This was a single-center retrospective study exam-ining patients with Ph+ ALL who underwent HCT from 2000-2019. The primary endpoint was progression free survival (PFS), while secondary endpoints include overall survival (OS), graft versus host disease free survival (GRFS), non-relapse mortality (NRM), and cumulative incidence of relapse (CIR), 

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Long-Term Efficacy and Safety of Zanubrutinib in Patients with Relapsed/Refractory (R/R) Marginal Zone Lymphoma (MZL): Final Analysis of the Magnolia (BGB-3111-214) Trial

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