SlideShare ist ein Scribd-Unternehmen logo
1 von 31
Downloaden Sie, um offline zu lesen
Three major advancements in the field of 
Lymphoma Treatment in the 21st century 
Dr. Raymond SM Wong 
Department of Medicine & Therapeutics 
Prince of Wales Hospital 
The Chinese University of Hong Kong
Major Advancements in Lymphoma Treatment 
1. Improvement of efficacy of antibody-directed 
therapy 
• Antibody-drug conjugates 
2. Targeting B-cell receptor (BCR) signaling 
• BCR Signal Transduction Inhibitor Therapy 
3. Combating the epigenome 
• Epigenetic drugs
Monoclonal antibody for lymphoma
Overall Survival among 399 Patients with DLBCL Assigned to 
CHOP vs R-CHOP 
Coiffier B et al. N Engl J Med 2002;346:235-242.
Antibody-Drug Conjugates 
• Most monoclonal antibodies are not sufficiently potent to be 
therapeutically active on their own 
• Antibody–drug conjugates (ADCs) use antibodies to deliver a 
potent cytotoxic compound selectively to tumor cells, thus 
improving the therapeutic index of chemotherapeutic agents 
• Becoming an increasingly important sub-class of antibody-related 
therapeutics
Brentuximab vedotin 
• Anti-CD30 monoclonal antibody 
linked to monomethyl auristatin 
E (MMAE), a microtubule-disrupting 
agent, by a cleavable 
linker 
• Approved for use in relapsed 
classical Hodgkin lymphoma’s 
and in systemic anaplastic large 
cell lymphoma
Hodgkin’s Lymphoma 
• Conventional treatment relies on 
standard chemotherapy, radiation 
therapy, and autologous or allogeneic 
stem cell transplantation in cases of 
relapsed disease 
• In spite of a high cure rate, patients 
who are not cured with first- or second-line 
therapy, including stem cell 
transplantation, have an estimated 
median survival of < 3 years 
• No new drugs have been approved for 
HL by the US FDA in more than 30 years
Targeted therapy of HRS cells 
Younes A Hematology 2009;2009:507-519 
©2009 by American Society of Hematology 
• HRS cells express a 
variety of receptors 
and antigens that can 
be targeted by 
monoclonal 
antibodies. 
• Many of these 
receptors trigger well-defined 
signaling 
pathways that 
promote HRS cell 
survival and can be 
targeted by a variety 
of small molecules.
Mechanism of action of brentuximab vedotin 
Siddiqi T, et al, 2014
Pivotal Phase II Study of Brentuximab Vedotin for Patients 
With Relapsed or Refractory Hodgkin's Lymphoma 
Younes A, et al. JCO 2012
Response rate of select therapies in HL 
Batlevi C L , and Younes A Hematology 2013;2013:394-399 
©2013 by American Society of Hematology
Development of novel antibody-drug conjugates 
Siddiqi T, et al, 2014
Targeting B-cell receptor signaling 
Fowler N and Davis E. Hematology 2013
B-cell receptor signaling 
Bruton’s tyrosine kinase (BTK) 
• is a non-receptor kinase 
• its function is essential to 
normal B cells 
• is phosphorylated by SYK 
and then phosphorylates 
phospholipase Cγ2, leading 
to activation of protein 
kinase C beta and, in turn, 
CARD11 
Phosphoinositide 3-kinase (PI3K) 
• PI3K/AKT pathway is critical 
for essential cellular 
processes such as 
metabolism, growth, and 
proliferation 
• The p110 delta and p110 
gamma isoforms are 
expressed primarily in cells 
of hematopoietic origin
Mechanism of Action of Idelalisib and Ibrutinib 
Fruman DA, Cantley LC. N Engl J Med 2014;370:1061-1062.
Ibrutinib 
• An orally available, selective inhibitor of Bruton's tyrosine 
kinase. 
• It blocks BCR signaling in normal peripheral B cells and 
showed antitumor activity in several types of non-Hodgkin's 
lymphoma 
• Bruton tyrosine kinase is 
commonly overexpressed 
in mantle cell lymphoma
Ibrutinib phase 2 trial in mantle cell lymphoma 
Wang ML et al. N Engl J Med 
2013;369:507-516.
Idelalisib (GS-1101 or CAL-101) 
• An oral agent that primarily 
inhibits the delta isoform of PI3K 
• Just been approved by FDA to treat 
patients with 
• relapsed chronic lymphocytic 
leukemia (CLL) 
• relapsed follicular lymphoma 
(FL) 
• relapsed small lymphocytic 
lymphoma (SLL)
Phase 2 study of Idelalisib for indolent lymphoma 
Gopal AK, et al. NEJM 2014
Idelalisib for indolent lymphoma 
Gopal AK, et al. NEJM 2014
BCR Inhibitors
BCR Inhibitors 
Fowler N and Davis E. Hematology 2013
Targeting the epigenome 
• Recurrent mutations in epigenetic enzymes, such as chromatin 
modifiers and DNA methyltransferases, have been discovered 
in NHL
Alteractions of chromatin states in NHL due to 
mutations in chromatin-related protein 
• CRC: chromatin remodeler 
• DNMT: DNA 
methyltransferase 
• HAT: Histone 
acetyltransferase 
• HDAC: Histone deacetylase 
• HMT: Histone 
methyltransferase 
• PcG: polycomb group 
• TF: Transcription factor 
Hassler MR, et al. 2013
Vorinostat 
• an histone deacetylase inhibitor 
• also known as suberoylanilide hydroxamic acid, SAHA 
• Approved by FDA for the treatment of cutaneous T-cell 
lymphoma failed other treatment
Phase 2 trial of Vorinostat for CTCL 
Duvic M, et al. Blood 2007
Phase 2 trial of Vorinostat for CTCL 
Duvic M, et al. Blood 2007
Selected epigenetic drugs in clinical development 
for DLBCL 
Cerchietti L, et al. Hematology 2013
Hassler MR, et 
al. 2013
Summary 
• The rapid improvement of our understanding of the molecular 
basis of various lymphomas have led to the development of 
many new treatment 
• Many of these new agents have shown promising results in 
clinical trials and are going into clinical practice 
• Despite early success as well as substantial and durable 
responses in some patients, there is still much work to be done 
• The greatest impact these new treatment will likely to come 
from combination therapy, possibly in the frontline setting 
• Further studies are needed to answer these key questions and 
ultimately lead to the development of highly effective 
mechanism based drug regimens
The End 
Thank you

Weitere ähnliche Inhalte

Was ist angesagt?

donor selection in Haplo Transplant
donor selection in Haplo Transplantdonor selection in Haplo Transplant
donor selection in Haplo Transplantspa718
 
smoldering myeloma
smoldering myelomasmoldering myeloma
smoldering myelomaspa718
 
Perrotti A.P. From empiric therapy to guide lines of silent and aggressive li...
Perrotti A.P. From empiric therapy to guide lines of silent and aggressive li...Perrotti A.P. From empiric therapy to guide lines of silent and aggressive li...
Perrotti A.P. From empiric therapy to guide lines of silent and aggressive li...Gianfranco Tammaro
 
Is it time to consider targeted therapy in combination for newly diagnosed AML?
Is it time to consider targeted therapy in combination for newly diagnosed AML?Is it time to consider targeted therapy in combination for newly diagnosed AML?
Is it time to consider targeted therapy in combination for newly diagnosed AML?spa718
 
Relapsed Myeloma
Relapsed MyelomaRelapsed Myeloma
Relapsed Myelomaspa718
 
Slide deck updates on cml (1)
Slide deck updates on cml (1)Slide deck updates on cml (1)
Slide deck updates on cml (1)madurai
 
Recent Advances In The Development Of Innovative Therapies The Celgene Pipeline
Recent Advances In The Development  Of Innovative Therapies The Celgene PipelineRecent Advances In The Development  Of Innovative Therapies The Celgene Pipeline
Recent Advances In The Development Of Innovative Therapies The Celgene Pipelinespa718
 
Follicular lymphoma
Follicular lymphomaFollicular lymphoma
Follicular lymphomahatem honor
 
Cellular Therapy for multiple myeloma
Cellular Therapy for multiple myelomaCellular Therapy for multiple myeloma
Cellular Therapy for multiple myelomaspa718
 
aplastic anemia
aplastic anemiaaplastic anemia
aplastic anemiaspa718
 
8 jason westin
8 jason westin8 jason westin
8 jason westinspa718
 
smoldering myeloma
smoldering myelomasmoldering myeloma
smoldering myelomaspa718
 
Ideal induction regimen for AML in adolescents and young adults 
Ideal induction regimen for AML in adolescents and young adults Ideal induction regimen for AML in adolescents and young adults 
Ideal induction regimen for AML in adolescents and young adults spa718
 
ASH 2015 NHL clinical update
ASH 2015 NHL clinical updateASH 2015 NHL clinical update
ASH 2015 NHL clinical updateChandan K Das
 
Elderly Acute Myeloid Leukemia
Elderly Acute Myeloid LeukemiaElderly Acute Myeloid Leukemia
Elderly Acute Myeloid Leukemiaspa718
 
Peripheral Blood Stem Cell Transplant
Peripheral Blood Stem Cell TransplantPeripheral Blood Stem Cell Transplant
Peripheral Blood Stem Cell Transplantspa718
 
Acute Lymphoblastic Lymphoma: Treatment Update
Acute Lymphoblastic Lymphoma: Treatment UpdateAcute Lymphoblastic Lymphoma: Treatment Update
Acute Lymphoblastic Lymphoma: Treatment Updatespa718
 
Targeted therapy for Hodgkin’s Lymphoma
Targeted therapy for Hodgkin’s LymphomaTargeted therapy for Hodgkin’s Lymphoma
Targeted therapy for Hodgkin’s Lymphomaspa718
 
FOLLICULAR LYMPHOMA; UPDATES ON TREATMENT STRATEGIES
FOLLICULAR LYMPHOMA; UPDATES  ON TREATMENT STRATEGIESFOLLICULAR LYMPHOMA; UPDATES  ON TREATMENT STRATEGIES
FOLLICULAR LYMPHOMA; UPDATES ON TREATMENT STRATEGIESspa718
 
Role of Stem cell transplant in Chronic Myeloid Leukemia in present era
Role of Stem cell transplant in Chronic Myeloid Leukemia in present eraRole of Stem cell transplant in Chronic Myeloid Leukemia in present era
Role of Stem cell transplant in Chronic Myeloid Leukemia in present eraAlok Gupta
 

Was ist angesagt? (20)

donor selection in Haplo Transplant
donor selection in Haplo Transplantdonor selection in Haplo Transplant
donor selection in Haplo Transplant
 
smoldering myeloma
smoldering myelomasmoldering myeloma
smoldering myeloma
 
Perrotti A.P. From empiric therapy to guide lines of silent and aggressive li...
Perrotti A.P. From empiric therapy to guide lines of silent and aggressive li...Perrotti A.P. From empiric therapy to guide lines of silent and aggressive li...
Perrotti A.P. From empiric therapy to guide lines of silent and aggressive li...
 
Is it time to consider targeted therapy in combination for newly diagnosed AML?
Is it time to consider targeted therapy in combination for newly diagnosed AML?Is it time to consider targeted therapy in combination for newly diagnosed AML?
Is it time to consider targeted therapy in combination for newly diagnosed AML?
 
Relapsed Myeloma
Relapsed MyelomaRelapsed Myeloma
Relapsed Myeloma
 
Slide deck updates on cml (1)
Slide deck updates on cml (1)Slide deck updates on cml (1)
Slide deck updates on cml (1)
 
Recent Advances In The Development Of Innovative Therapies The Celgene Pipeline
Recent Advances In The Development  Of Innovative Therapies The Celgene PipelineRecent Advances In The Development  Of Innovative Therapies The Celgene Pipeline
Recent Advances In The Development Of Innovative Therapies The Celgene Pipeline
 
Follicular lymphoma
Follicular lymphomaFollicular lymphoma
Follicular lymphoma
 
Cellular Therapy for multiple myeloma
Cellular Therapy for multiple myelomaCellular Therapy for multiple myeloma
Cellular Therapy for multiple myeloma
 
aplastic anemia
aplastic anemiaaplastic anemia
aplastic anemia
 
8 jason westin
8 jason westin8 jason westin
8 jason westin
 
smoldering myeloma
smoldering myelomasmoldering myeloma
smoldering myeloma
 
Ideal induction regimen for AML in adolescents and young adults 
Ideal induction regimen for AML in adolescents and young adults Ideal induction regimen for AML in adolescents and young adults 
Ideal induction regimen for AML in adolescents and young adults 
 
ASH 2015 NHL clinical update
ASH 2015 NHL clinical updateASH 2015 NHL clinical update
ASH 2015 NHL clinical update
 
Elderly Acute Myeloid Leukemia
Elderly Acute Myeloid LeukemiaElderly Acute Myeloid Leukemia
Elderly Acute Myeloid Leukemia
 
Peripheral Blood Stem Cell Transplant
Peripheral Blood Stem Cell TransplantPeripheral Blood Stem Cell Transplant
Peripheral Blood Stem Cell Transplant
 
Acute Lymphoblastic Lymphoma: Treatment Update
Acute Lymphoblastic Lymphoma: Treatment UpdateAcute Lymphoblastic Lymphoma: Treatment Update
Acute Lymphoblastic Lymphoma: Treatment Update
 
Targeted therapy for Hodgkin’s Lymphoma
Targeted therapy for Hodgkin’s LymphomaTargeted therapy for Hodgkin’s Lymphoma
Targeted therapy for Hodgkin’s Lymphoma
 
FOLLICULAR LYMPHOMA; UPDATES ON TREATMENT STRATEGIES
FOLLICULAR LYMPHOMA; UPDATES  ON TREATMENT STRATEGIESFOLLICULAR LYMPHOMA; UPDATES  ON TREATMENT STRATEGIES
FOLLICULAR LYMPHOMA; UPDATES ON TREATMENT STRATEGIES
 
Role of Stem cell transplant in Chronic Myeloid Leukemia in present era
Role of Stem cell transplant in Chronic Myeloid Leukemia in present eraRole of Stem cell transplant in Chronic Myeloid Leukemia in present era
Role of Stem cell transplant in Chronic Myeloid Leukemia in present era
 

Andere mochten auch

How Radiation Therapy Is Used in the Treatment of Lymphoma
How Radiation Therapy Is Used in the Treatment of Lymphoma How Radiation Therapy Is Used in the Treatment of Lymphoma
How Radiation Therapy Is Used in the Treatment of Lymphoma Dana-Farber Cancer Institute
 
Hodgkins & Non-Hodgkins Lymphomas
Hodgkins & Non-Hodgkins LymphomasHodgkins & Non-Hodgkins Lymphomas
Hodgkins & Non-Hodgkins LymphomasDinoosh De Livera
 
Haematological Malignancies
Haematological MalignanciesHaematological Malignancies
Haematological Malignanciesmeducationdotnet
 
Clinical Trials, Emerging New Drugs and Future Concepts in the Treatment of L...
Clinical Trials, Emerging New Drugs and Future Concepts in the Treatment of L...Clinical Trials, Emerging New Drugs and Future Concepts in the Treatment of L...
Clinical Trials, Emerging New Drugs and Future Concepts in the Treatment of L...Dana-Farber Cancer Institute
 
Blood Cancers: An Overview
Blood Cancers: An OverviewBlood Cancers: An Overview
Blood Cancers: An OverviewQueens Library
 
Haematological malignancies - part one
Haematological malignancies - part oneHaematological malignancies - part one
Haematological malignancies - part oneess_online
 
principles of chemotherapy
principles of chemotherapyprinciples of chemotherapy
principles of chemotherapyDR NILESH KATOLE
 
Radiotherapy Lymphomas
Radiotherapy LymphomasRadiotherapy Lymphomas
Radiotherapy Lymphomasfondas vakalis
 
Hodgkin’s Lymphoma
Hodgkin’s  LymphomaHodgkin’s  Lymphoma
Hodgkin’s LymphomaArnab Bose
 
non-hodgkin’s-lymphoma
non-hodgkin’s-lymphomanon-hodgkin’s-lymphoma
non-hodgkin’s-lymphomaChandan N
 
Hodgkin lymphoma
Hodgkin lymphomaHodgkin lymphoma
Hodgkin lymphomatashagarwal
 
Hodgkin’S And Non Hodgkin’S Lymphoma
Hodgkin’S And Non Hodgkin’S LymphomaHodgkin’S And Non Hodgkin’S Lymphoma
Hodgkin’S And Non Hodgkin’S Lymphomafondas vakalis
 
Non hodgkin lymphoma
Non hodgkin lymphomaNon hodgkin lymphoma
Non hodgkin lymphomatashagarwal
 

Andere mochten auch (20)

An Overview of Lymphoma Treatment
An Overview of Lymphoma TreatmentAn Overview of Lymphoma Treatment
An Overview of Lymphoma Treatment
 
How Radiation Therapy Is Used in the Treatment of Lymphoma
How Radiation Therapy Is Used in the Treatment of Lymphoma How Radiation Therapy Is Used in the Treatment of Lymphoma
How Radiation Therapy Is Used in the Treatment of Lymphoma
 
Hodgkins & Non-Hodgkins Lymphomas
Hodgkins & Non-Hodgkins LymphomasHodgkins & Non-Hodgkins Lymphomas
Hodgkins & Non-Hodgkins Lymphomas
 
Lymphoma
LymphomaLymphoma
Lymphoma
 
Rt in lymphoma
Rt in lymphomaRt in lymphoma
Rt in lymphoma
 
Haematological Malignancies
Haematological MalignanciesHaematological Malignancies
Haematological Malignancies
 
Lymphomas 5
Lymphomas 5Lymphomas 5
Lymphomas 5
 
Clinical Trials, Emerging New Drugs and Future Concepts in the Treatment of L...
Clinical Trials, Emerging New Drugs and Future Concepts in the Treatment of L...Clinical Trials, Emerging New Drugs and Future Concepts in the Treatment of L...
Clinical Trials, Emerging New Drugs and Future Concepts in the Treatment of L...
 
Blood Cancers: An Overview
Blood Cancers: An OverviewBlood Cancers: An Overview
Blood Cancers: An Overview
 
Haematological malignancies - part one
Haematological malignancies - part oneHaematological malignancies - part one
Haematological malignancies - part one
 
principles of chemotherapy
principles of chemotherapyprinciples of chemotherapy
principles of chemotherapy
 
Radiotherapy Lymphomas
Radiotherapy LymphomasRadiotherapy Lymphomas
Radiotherapy Lymphomas
 
Hodgkin’s Lymphoma
Hodgkin’s  LymphomaHodgkin’s  Lymphoma
Hodgkin’s Lymphoma
 
non-hodgkin’s-lymphoma
non-hodgkin’s-lymphomanon-hodgkin’s-lymphoma
non-hodgkin’s-lymphoma
 
Lymphoma
Lymphoma Lymphoma
Lymphoma
 
Hodgkin lymphoma
Hodgkin lymphomaHodgkin lymphoma
Hodgkin lymphoma
 
Hodgkin’S And Non Hodgkin’S Lymphoma
Hodgkin’S And Non Hodgkin’S LymphomaHodgkin’S And Non Hodgkin’S Lymphoma
Hodgkin’S And Non Hodgkin’S Lymphoma
 
Lymphoma
LymphomaLymphoma
Lymphoma
 
Non hodgkin lymphoma
Non hodgkin lymphomaNon hodgkin lymphoma
Non hodgkin lymphoma
 
Lymphoma
LymphomaLymphoma
Lymphoma
 

Ähnlich wie Lymphoma

Evidence-Based Clinical Updates in the Treatment of Patients with Relapsed/Re...
Evidence-Based Clinical Updates in the Treatment of Patients with Relapsed/Re...Evidence-Based Clinical Updates in the Treatment of Patients with Relapsed/Re...
Evidence-Based Clinical Updates in the Treatment of Patients with Relapsed/Re...Carevive
 
Metronomic Chemotherapy
Metronomic ChemotherapyMetronomic Chemotherapy
Metronomic ChemotherapySonali Karekar
 
Upfront treatment of CML: How to select TKI?.pptx
Upfront treatment of CML:How to select TKI?.pptxUpfront treatment of CML:How to select TKI?.pptx
Upfront treatment of CML: How to select TKI?.pptxPritish Chandra Patra
 
Crohns symposium mathew philps beyond biologicals
Crohns symposium mathew philps  beyond biologicalsCrohns symposium mathew philps  beyond biologicals
Crohns symposium mathew philps beyond biologicalsrrsolution
 
К.Тверской, Pfizer
К.Тверской, Pfizer К.Тверской, Pfizer
К.Тверской, Pfizer Pharmcluster
 
Unmet need in multiple myeloma
Unmet need in multiple myelomaUnmet need in multiple myeloma
Unmet need in multiple myelomaPLMMedical
 
Lenalidomide maintenance compared with placebo in responding elderly
Lenalidomide maintenance compared with placebo in responding elderlyLenalidomide maintenance compared with placebo in responding elderly
Lenalidomide maintenance compared with placebo in responding elderlyravi jaiswal
 
Stem Cell Transplantation in Hodgkin’s Lymphoma Past, Present and Future
Stem Cell Transplantation in  Hodgkin’s Lymphoma  Past, Present and FutureStem Cell Transplantation in  Hodgkin’s Lymphoma  Past, Present and Future
Stem Cell Transplantation in Hodgkin’s Lymphoma Past, Present and FutureAmir Abbas Hedayati Asl
 
cancer genetics, tumor marker and targeted therapy in cancer
cancer genetics, tumor marker and targeted therapy in cancercancer genetics, tumor marker and targeted therapy in cancer
cancer genetics, tumor marker and targeted therapy in cancerShivshankar Badole
 
University of Missouri - Columbia, POSH Inhibitor-Based Cancer Therapy
University of Missouri - Columbia, POSH Inhibitor-Based Cancer TherapyUniversity of Missouri - Columbia, POSH Inhibitor-Based Cancer Therapy
University of Missouri - Columbia, POSH Inhibitor-Based Cancer Therapykphodel
 
The Importance of Biomarkers in Hematology/Oncology Drug Development - Steven...
The Importance of Biomarkers in Hematology/Oncology Drug Development - Steven...The Importance of Biomarkers in Hematology/Oncology Drug Development - Steven...
The Importance of Biomarkers in Hematology/Oncology Drug Development - Steven...Life Sciences Network marcus evans
 
TARGETED DRUG DELIVERY IN CANCER
TARGETED DRUG DELIVERY IN CANCERTARGETED DRUG DELIVERY IN CANCER
TARGETED DRUG DELIVERY IN CANCERSanthi Dasari
 
TARGETED DRUG DELIVERY IN CANCER
TARGETED DRUG DELIVERY IN CANCERTARGETED DRUG DELIVERY IN CANCER
TARGETED DRUG DELIVERY IN CANCERSanthi Dasari
 
TARGETED DRUG DELIVERY IN CANCER
TARGETED DRUG DELIVERY IN CANCERTARGETED DRUG DELIVERY IN CANCER
TARGETED DRUG DELIVERY IN CANCERTamil Jothi
 
Io combos and the big stick
Io combos and the big stick Io combos and the big stick
Io combos and the big stick Paul D. Rennert
 
Approved Programmed Cell Death-1 Inhibitors in Hodgkin Lymphoma: The first Br...
Approved Programmed Cell Death-1 Inhibitors in Hodgkin Lymphoma: The first Br...Approved Programmed Cell Death-1 Inhibitors in Hodgkin Lymphoma: The first Br...
Approved Programmed Cell Death-1 Inhibitors in Hodgkin Lymphoma: The first Br...asclepiuspdfs
 
Cancer chemotherapy for medical students
Cancer chemotherapy for medical studentsCancer chemotherapy for medical students
Cancer chemotherapy for medical studentstaklo simeneh
 

Ähnlich wie Lymphoma (20)

Evidence-Based Clinical Updates in the Treatment of Patients with Relapsed/Re...
Evidence-Based Clinical Updates in the Treatment of Patients with Relapsed/Re...Evidence-Based Clinical Updates in the Treatment of Patients with Relapsed/Re...
Evidence-Based Clinical Updates in the Treatment of Patients with Relapsed/Re...
 
Metronomic Chemotherapy
Metronomic ChemotherapyMetronomic Chemotherapy
Metronomic Chemotherapy
 
Upfront treatment of CML: How to select TKI?.pptx
Upfront treatment of CML:How to select TKI?.pptxUpfront treatment of CML:How to select TKI?.pptx
Upfront treatment of CML: How to select TKI?.pptx
 
Crohns symposium mathew philps beyond biologicals
Crohns symposium mathew philps  beyond biologicalsCrohns symposium mathew philps  beyond biologicals
Crohns symposium mathew philps beyond biologicals
 
К.Тверской, Pfizer
К.Тверской, Pfizer К.Тверской, Pfizer
К.Тверской, Pfizer
 
Unmet need in multiple myeloma
Unmet need in multiple myelomaUnmet need in multiple myeloma
Unmet need in multiple myeloma
 
Lenalidomide maintenance compared with placebo in responding elderly
Lenalidomide maintenance compared with placebo in responding elderlyLenalidomide maintenance compared with placebo in responding elderly
Lenalidomide maintenance compared with placebo in responding elderly
 
Stem Cell Transplantation in Hodgkin’s Lymphoma Past, Present and Future
Stem Cell Transplantation in  Hodgkin’s Lymphoma  Past, Present and FutureStem Cell Transplantation in  Hodgkin’s Lymphoma  Past, Present and Future
Stem Cell Transplantation in Hodgkin’s Lymphoma Past, Present and Future
 
New Horizons for Advanced Endometrial Cancer Treatment: Utilizing Innovative ...
New Horizons for Advanced Endometrial Cancer Treatment: Utilizing Innovative ...New Horizons for Advanced Endometrial Cancer Treatment: Utilizing Innovative ...
New Horizons for Advanced Endometrial Cancer Treatment: Utilizing Innovative ...
 
cancer genetics, tumor marker and targeted therapy in cancer
cancer genetics, tumor marker and targeted therapy in cancercancer genetics, tumor marker and targeted therapy in cancer
cancer genetics, tumor marker and targeted therapy in cancer
 
Best of ASH 2016
Best of ASH 2016Best of ASH 2016
Best of ASH 2016
 
University of Missouri - Columbia, POSH Inhibitor-Based Cancer Therapy
University of Missouri - Columbia, POSH Inhibitor-Based Cancer TherapyUniversity of Missouri - Columbia, POSH Inhibitor-Based Cancer Therapy
University of Missouri - Columbia, POSH Inhibitor-Based Cancer Therapy
 
The Importance of Biomarkers in Hematology/Oncology Drug Development - Steven...
The Importance of Biomarkers in Hematology/Oncology Drug Development - Steven...The Importance of Biomarkers in Hematology/Oncology Drug Development - Steven...
The Importance of Biomarkers in Hematology/Oncology Drug Development - Steven...
 
TARGETED DRUG DELIVERY IN CANCER
TARGETED DRUG DELIVERY IN CANCERTARGETED DRUG DELIVERY IN CANCER
TARGETED DRUG DELIVERY IN CANCER
 
TARGETED DRUG DELIVERY IN CANCER
TARGETED DRUG DELIVERY IN CANCERTARGETED DRUG DELIVERY IN CANCER
TARGETED DRUG DELIVERY IN CANCER
 
TARGETED DRUG DELIVERY IN CANCER
TARGETED DRUG DELIVERY IN CANCERTARGETED DRUG DELIVERY IN CANCER
TARGETED DRUG DELIVERY IN CANCER
 
Io combos and the big stick
Io combos and the big stick Io combos and the big stick
Io combos and the big stick
 
Approved Programmed Cell Death-1 Inhibitors in Hodgkin Lymphoma: The first Br...
Approved Programmed Cell Death-1 Inhibitors in Hodgkin Lymphoma: The first Br...Approved Programmed Cell Death-1 Inhibitors in Hodgkin Lymphoma: The first Br...
Approved Programmed Cell Death-1 Inhibitors in Hodgkin Lymphoma: The first Br...
 
Cancer chemotherapy for medical students
Cancer chemotherapy for medical studentsCancer chemotherapy for medical students
Cancer chemotherapy for medical students
 
molecular medicine.pptx
molecular medicine.pptxmolecular medicine.pptx
molecular medicine.pptx
 

Mehr von spa718

1600 1620 siwanon jirawatnotai
1600 1620 siwanon jirawatnotai1600 1620 siwanon jirawatnotai
1600 1620 siwanon jirawatnotaispa718
 
Controversies in hepato-biliary surgery
Controversies in hepato-biliary surgery Controversies in hepato-biliary surgery
Controversies in hepato-biliary surgery spa718
 
Controversies in Colorectal Cancer
Controversies in Colorectal CancerControversies in Colorectal Cancer
Controversies in Colorectal Cancerspa718
 
Pancreatic Cancer
Pancreatic CancerPancreatic Cancer
Pancreatic Cancerspa718
 
Chemoradiation vs Surgery for rectal cancer
Chemoradiation vs Surgery for rectal cancerChemoradiation vs Surgery for rectal cancer
Chemoradiation vs Surgery for rectal cancerspa718
 
Cholangiocarcinoma
CholangiocarcinomaCholangiocarcinoma
Cholangiocarcinomaspa718
 
Immunotherapy for Colorectal Cancer
Immunotherapy for Colorectal CancerImmunotherapy for Colorectal Cancer
Immunotherapy for Colorectal Cancerspa718
 
Surgical Approach to Non Small Cell Lung Cancer
Surgical Approach to Non Small Cell Lung CancerSurgical Approach to Non Small Cell Lung Cancer
Surgical Approach to Non Small Cell Lung Cancerspa718
 
Role of Radiation Therapy for Lung Cancer
Role of Radiation Therapy for Lung CancerRole of Radiation Therapy for Lung Cancer
Role of Radiation Therapy for Lung Cancerspa718
 
Update on Management of Triple Negative Breast Cancer
Update on Management of Triple Negative Breast CancerUpdate on Management of Triple Negative Breast Cancer
Update on Management of Triple Negative Breast Cancerspa718
 
Technical Advances in radiotherapy for Lung (and liver) Cancer
Technical Advances in radiotherapy for Lung (and liver) CancerTechnical Advances in radiotherapy for Lung (and liver) Cancer
Technical Advances in radiotherapy for Lung (and liver) Cancerspa718
 
Controversies in Surgical Approach to Breast Cancer
Controversies in Surgical Approach to Breast CancerControversies in Surgical Approach to Breast Cancer
Controversies in Surgical Approach to Breast Cancerspa718
 
ImmunoOncology in Lung Cancer
ImmunoOncology in Lung CancerImmunoOncology in Lung Cancer
ImmunoOncology in Lung Cancerspa718
 
Breast Cancer Highlights: ASCO 2015
Breast Cancer Highlights: ASCO 2015Breast Cancer Highlights: ASCO 2015
Breast Cancer Highlights: ASCO 2015spa718
 
Updates in Radiotherapy for Breast Cancer
Updates in Radiotherapy for Breast CancerUpdates in Radiotherapy for Breast Cancer
Updates in Radiotherapy for Breast Cancerspa718
 
Regulatory T Cells and GVHD
Regulatory T Cells and GVHDRegulatory T Cells and GVHD
Regulatory T Cells and GVHDspa718
 
Immunotherapy for Multiple Myeloma
Immunotherapy for Multiple MyelomaImmunotherapy for Multiple Myeloma
Immunotherapy for Multiple Myelomaspa718
 
NHL immunotherapy
NHL immunotherapyNHL immunotherapy
NHL immunotherapyspa718
 
AML and Cell Therapy
AML and Cell TherapyAML and Cell Therapy
AML and Cell Therapyspa718
 
Allogeneic HSCT in Elderly
Allogeneic HSCT in ElderlyAllogeneic HSCT in Elderly
Allogeneic HSCT in Elderlyspa718
 

Mehr von spa718 (20)

1600 1620 siwanon jirawatnotai
1600 1620 siwanon jirawatnotai1600 1620 siwanon jirawatnotai
1600 1620 siwanon jirawatnotai
 
Controversies in hepato-biliary surgery
Controversies in hepato-biliary surgery Controversies in hepato-biliary surgery
Controversies in hepato-biliary surgery
 
Controversies in Colorectal Cancer
Controversies in Colorectal CancerControversies in Colorectal Cancer
Controversies in Colorectal Cancer
 
Pancreatic Cancer
Pancreatic CancerPancreatic Cancer
Pancreatic Cancer
 
Chemoradiation vs Surgery for rectal cancer
Chemoradiation vs Surgery for rectal cancerChemoradiation vs Surgery for rectal cancer
Chemoradiation vs Surgery for rectal cancer
 
Cholangiocarcinoma
CholangiocarcinomaCholangiocarcinoma
Cholangiocarcinoma
 
Immunotherapy for Colorectal Cancer
Immunotherapy for Colorectal CancerImmunotherapy for Colorectal Cancer
Immunotherapy for Colorectal Cancer
 
Surgical Approach to Non Small Cell Lung Cancer
Surgical Approach to Non Small Cell Lung CancerSurgical Approach to Non Small Cell Lung Cancer
Surgical Approach to Non Small Cell Lung Cancer
 
Role of Radiation Therapy for Lung Cancer
Role of Radiation Therapy for Lung CancerRole of Radiation Therapy for Lung Cancer
Role of Radiation Therapy for Lung Cancer
 
Update on Management of Triple Negative Breast Cancer
Update on Management of Triple Negative Breast CancerUpdate on Management of Triple Negative Breast Cancer
Update on Management of Triple Negative Breast Cancer
 
Technical Advances in radiotherapy for Lung (and liver) Cancer
Technical Advances in radiotherapy for Lung (and liver) CancerTechnical Advances in radiotherapy for Lung (and liver) Cancer
Technical Advances in radiotherapy for Lung (and liver) Cancer
 
Controversies in Surgical Approach to Breast Cancer
Controversies in Surgical Approach to Breast CancerControversies in Surgical Approach to Breast Cancer
Controversies in Surgical Approach to Breast Cancer
 
ImmunoOncology in Lung Cancer
ImmunoOncology in Lung CancerImmunoOncology in Lung Cancer
ImmunoOncology in Lung Cancer
 
Breast Cancer Highlights: ASCO 2015
Breast Cancer Highlights: ASCO 2015Breast Cancer Highlights: ASCO 2015
Breast Cancer Highlights: ASCO 2015
 
Updates in Radiotherapy for Breast Cancer
Updates in Radiotherapy for Breast CancerUpdates in Radiotherapy for Breast Cancer
Updates in Radiotherapy for Breast Cancer
 
Regulatory T Cells and GVHD
Regulatory T Cells and GVHDRegulatory T Cells and GVHD
Regulatory T Cells and GVHD
 
Immunotherapy for Multiple Myeloma
Immunotherapy for Multiple MyelomaImmunotherapy for Multiple Myeloma
Immunotherapy for Multiple Myeloma
 
NHL immunotherapy
NHL immunotherapyNHL immunotherapy
NHL immunotherapy
 
AML and Cell Therapy
AML and Cell TherapyAML and Cell Therapy
AML and Cell Therapy
 
Allogeneic HSCT in Elderly
Allogeneic HSCT in ElderlyAllogeneic HSCT in Elderly
Allogeneic HSCT in Elderly
 

Lymphoma

  • 1. Three major advancements in the field of Lymphoma Treatment in the 21st century Dr. Raymond SM Wong Department of Medicine & Therapeutics Prince of Wales Hospital The Chinese University of Hong Kong
  • 2. Major Advancements in Lymphoma Treatment 1. Improvement of efficacy of antibody-directed therapy • Antibody-drug conjugates 2. Targeting B-cell receptor (BCR) signaling • BCR Signal Transduction Inhibitor Therapy 3. Combating the epigenome • Epigenetic drugs
  • 4. Overall Survival among 399 Patients with DLBCL Assigned to CHOP vs R-CHOP Coiffier B et al. N Engl J Med 2002;346:235-242.
  • 5. Antibody-Drug Conjugates • Most monoclonal antibodies are not sufficiently potent to be therapeutically active on their own • Antibody–drug conjugates (ADCs) use antibodies to deliver a potent cytotoxic compound selectively to tumor cells, thus improving the therapeutic index of chemotherapeutic agents • Becoming an increasingly important sub-class of antibody-related therapeutics
  • 6. Brentuximab vedotin • Anti-CD30 monoclonal antibody linked to monomethyl auristatin E (MMAE), a microtubule-disrupting agent, by a cleavable linker • Approved for use in relapsed classical Hodgkin lymphoma’s and in systemic anaplastic large cell lymphoma
  • 7. Hodgkin’s Lymphoma • Conventional treatment relies on standard chemotherapy, radiation therapy, and autologous or allogeneic stem cell transplantation in cases of relapsed disease • In spite of a high cure rate, patients who are not cured with first- or second-line therapy, including stem cell transplantation, have an estimated median survival of < 3 years • No new drugs have been approved for HL by the US FDA in more than 30 years
  • 8. Targeted therapy of HRS cells Younes A Hematology 2009;2009:507-519 ©2009 by American Society of Hematology • HRS cells express a variety of receptors and antigens that can be targeted by monoclonal antibodies. • Many of these receptors trigger well-defined signaling pathways that promote HRS cell survival and can be targeted by a variety of small molecules.
  • 9. Mechanism of action of brentuximab vedotin Siddiqi T, et al, 2014
  • 10. Pivotal Phase II Study of Brentuximab Vedotin for Patients With Relapsed or Refractory Hodgkin's Lymphoma Younes A, et al. JCO 2012
  • 11. Response rate of select therapies in HL Batlevi C L , and Younes A Hematology 2013;2013:394-399 ©2013 by American Society of Hematology
  • 12. Development of novel antibody-drug conjugates Siddiqi T, et al, 2014
  • 13. Targeting B-cell receptor signaling Fowler N and Davis E. Hematology 2013
  • 14. B-cell receptor signaling Bruton’s tyrosine kinase (BTK) • is a non-receptor kinase • its function is essential to normal B cells • is phosphorylated by SYK and then phosphorylates phospholipase Cγ2, leading to activation of protein kinase C beta and, in turn, CARD11 Phosphoinositide 3-kinase (PI3K) • PI3K/AKT pathway is critical for essential cellular processes such as metabolism, growth, and proliferation • The p110 delta and p110 gamma isoforms are expressed primarily in cells of hematopoietic origin
  • 15. Mechanism of Action of Idelalisib and Ibrutinib Fruman DA, Cantley LC. N Engl J Med 2014;370:1061-1062.
  • 16. Ibrutinib • An orally available, selective inhibitor of Bruton's tyrosine kinase. • It blocks BCR signaling in normal peripheral B cells and showed antitumor activity in several types of non-Hodgkin's lymphoma • Bruton tyrosine kinase is commonly overexpressed in mantle cell lymphoma
  • 17. Ibrutinib phase 2 trial in mantle cell lymphoma Wang ML et al. N Engl J Med 2013;369:507-516.
  • 18. Idelalisib (GS-1101 or CAL-101) • An oral agent that primarily inhibits the delta isoform of PI3K • Just been approved by FDA to treat patients with • relapsed chronic lymphocytic leukemia (CLL) • relapsed follicular lymphoma (FL) • relapsed small lymphocytic lymphoma (SLL)
  • 19. Phase 2 study of Idelalisib for indolent lymphoma Gopal AK, et al. NEJM 2014
  • 20. Idelalisib for indolent lymphoma Gopal AK, et al. NEJM 2014
  • 22. BCR Inhibitors Fowler N and Davis E. Hematology 2013
  • 23. Targeting the epigenome • Recurrent mutations in epigenetic enzymes, such as chromatin modifiers and DNA methyltransferases, have been discovered in NHL
  • 24. Alteractions of chromatin states in NHL due to mutations in chromatin-related protein • CRC: chromatin remodeler • DNMT: DNA methyltransferase • HAT: Histone acetyltransferase • HDAC: Histone deacetylase • HMT: Histone methyltransferase • PcG: polycomb group • TF: Transcription factor Hassler MR, et al. 2013
  • 25. Vorinostat • an histone deacetylase inhibitor • also known as suberoylanilide hydroxamic acid, SAHA • Approved by FDA for the treatment of cutaneous T-cell lymphoma failed other treatment
  • 26. Phase 2 trial of Vorinostat for CTCL Duvic M, et al. Blood 2007
  • 27. Phase 2 trial of Vorinostat for CTCL Duvic M, et al. Blood 2007
  • 28. Selected epigenetic drugs in clinical development for DLBCL Cerchietti L, et al. Hematology 2013
  • 29. Hassler MR, et al. 2013
  • 30. Summary • The rapid improvement of our understanding of the molecular basis of various lymphomas have led to the development of many new treatment • Many of these new agents have shown promising results in clinical trials and are going into clinical practice • Despite early success as well as substantial and durable responses in some patients, there is still much work to be done • The greatest impact these new treatment will likely to come from combination therapy, possibly in the frontline setting • Further studies are needed to answer these key questions and ultimately lead to the development of highly effective mechanism based drug regimens

Hinweis der Redaktion

  1. Targeted therapy of HRS cells. HRS cells express a variety of receptors and antigens that can be targeted by monoclonal antibodies. Many of these receptors trigger well-defined signaling pathways that promote HRS cell survival. These signaling pathways can be targeted by a variety of small molecules.
  2. Response rate of select therapies in HL.