Targeted Therapies

HIGHLIGHTS OF THE 1999 ASCO ANNUAL MEETING
HIGHLIGHTS OF THE 1999 ASH ANNUAL MEETING
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HIGHLIGHTS OF THE 2002 ASCO ANNUAL MEETING
HIGHLIGHTS OF THE 2002 ASH ANNUAL MEETING
HIGHLIGHTS OF THE 2003 ASCO ANNUAL MEETING
HIGHLIGHTS OF THE 2003 ASH ANNUAL MEETING
HIGHLIGHTS OF THE 2004 ASCO ANNUAL MEETING
HIGHLIGHTS OF THE 2004 ASH ANNUAL MEETING
HIGHLIGHTS OF THE 2005 ASCO ANNUAL MEETING
HIGHLIGHT OF THE 2005 ASH ANNUAL MEETING

ACUTE MYELOID LEUKEMIA
Gemtuzumab ozogamicin treatment in children
Mylotarg in first relapse
Nuclear factor (NF)-kB expression

ACUTE LYMPHOBLASTIC LEUKEMIA
Post-transplantation imatinib therapy

ACUTE PROMYELOCYTIC LEUKEMIA (APL)
Results of all-trans retinoic acid (ATRA) and anthracycline monochemotherapy in the elderly

ADOPTIVE IMMUNOTHERAPY
Antileukemic activity of allorestricted cytotoxic T lymphocytes (CTLs)

ALLOGENEIC STEM-CELL TRANSPLANTATION
Donor lymphocyte infusion (DLI) therapy for relapsed multiple myeloma
Therapy for renal-cell carcinoma

B-CELL LYMPHOMA
Homodimers of Rituxan
Idiotype (Id)-pulsed dendritic cell (DC) vaccination
Pretargeted radioimmunotherapy

BEVACIZUMAB
Front-line therapy for advanced colorectal cancer (advCRC)
Phase III study of combination therapy with IFL

BEVACIZUMAB THERAPY FOR BREAST CANCER
Bevacizumab plus capecitabine vs capecitabine alone

B-LYMPHOPROLIFERATIVE DISORDER
Anti-interleukin-6 (IL-6) treatment

BONE MARROW TRANSPLANTATION
Allospecific T-cell depletion
Improved outcome with T-cell depletion

BORTEZOMIB
Phase II studies in NHL
Studies in NHL

BREAST CANCER
Addition of trastuzumab to chemotherapy improves neoadjuvant results
Anti-HER2 monoclonal antibody (MAb) and geldanamycin (GA) immunoconjugate
Combination docetaxel and trastuzumab therapy
Effects of soluble recombinant human CD40 ligand
HER2/neu vaccine
Neoadjuvant trastuzumab
Phase II trial of ZD6474
Reactivated memory T cells
Recombinant human Anti-HER2 monoclonal antibody
Trastuzumab combined with chemotherapy
Trastuzumab combined with taxanes
Trastuzumab plus docetaxel
Trastuzumab plus chemotherapy in metastatic disease

CANCER VACCINES
Anti-carcinoembryonic antigen (CEA) immune response

CASTLEMAN DISEASE
Anti–interleukin (IL)-6 receptor antibody therapy

CERVICAL CANCER
Human leukocyte antigen class I gene mutations

CETUXIMAB
Activity against EGFR–negative colorectal cancer
Metastatic colorectal cancer (MCRC)
Phase II studies in squamous cell carcinoma of the head and neck and a report of hypomagnesemia

CHRONIC IDIOPATHIC THROMBOCYTOPENIC PURPURA
Efficacy of rituximab therapy

CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)
Campath-1H after fludarabine failure
CD20 levels and response to rituximab
CD40 activation of CLL-B-cells
Clinical significance of tumor necrosis factor-a (TNF-a) plasma level
Combination Campath-1H and fludarabine therapy
Early prediction of outcome to alemtuzumab therapy
Eradication of minimal residual disease with alemtuzumab
First-line treatment with Campath-1H
Fludarabine followed by alemtuzumab (Campath-1H)
Fludarabine, cyclophosphamide, rituximab (FCR) combination therapy
Fludarabine with concurrent or sequential rituximab
Fludarabine plus alemtuzumab
New Rituximab dosing regimens
Rituximab plus fludarabine

CHRONIC MYELOGENOUS LEUKEMIA (CML)
Donor lymphocyte infusions and durable remissions
Donor lymphocyte infusion (DLI) administration and GVHD
Effects of interferon-a (IFN) therapy on allogeneic bone marrow transplantation (BMT) outcomes
Effect of pretransplant interferon (IFN) therapy
High-dose imatinib mesylate after failure of interferon
Interferon effects
Leukemia-reactive cytotoxic T lymphocytes
Molecular heterogeneity in cytogenetic responders
Resistance to STI-571
T-cell-depleted (TCD) vs. non-T-cell depleted allogeneic bone marrow transplantation (BMT)
Polyethylene glycol (PEG) interferon (IFN)-a therapy
Response to imatinib mesylate
T-cell depletion combined with donor leukocyte infusion therapy
Treatment with interferon alpha (IFN-a) and low-dose cytarabine (ara-C)

COLON CANCER
Responses to an anti-idiotype monoclonal antibody
Edrecolomab adjuvant therapy does not provide clinical benefit

COLORECTAL CANCER
Bevacizumab plus fluorouracil (FU)/leucovorin (LV)

COLORECTAL CARCINOMA
Bevacizumab added to irinotecan, fluorouracil, and leucovorin (IFL)
Bevacizumab in combination with fluorouracil and leucovorin

CUTANEOUS T CELL LYMPHOMA
Interleukin-12 therapy

CYTOMEGALOVIRUS (CMV) INFECTION
Role of Campath-1H

DENDRITIC CELLS (DCS)
DC derived from acute myelogenous leukemia (AML) cells
Effects of vascular endothelial growth factor (VEGF)
Effects of interleukin-6 and macrophage colony-stimulating factor (M-CSF)

DENDRITIC CELL (DC) FUNCTION AND DEVELOPMENT
Effects of FLT3-ligand (FL) administration

EFFECT OF CANCER ON IMMUNE FUNCTION
Defective function of Langerhans cells (LC)

EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) INHIBITION
ZD1839 (Iressa)

EPSTEIN-BAR VIRUS-LYMPHOPROLIFERATIVE DISEASE (EBV-LPD)
Preemptive rituximab

FARNESYL TRANSFERASE INHIBITION
Tipifarnib

FLT3 INHIBITORS IN ACUTE MYELOID LEUKEMIA (AML)
Phase II studies of 2 novel agents

GEMTUZUMAB OZOGAMICIN
Association with hepatic venoocclusive disease

GLIOBLASTOMA
Response to kinase inhibitors

GRAFT-VERSUS-HOST DISEASE (GVHD)
Anti-CD147 therapy
CD6+ donor marrow T-cell depletion (TCD)
Effect of adding Campath-1G to the conditioning regimen
Granulocyte-colony stimulating factor (G-CSF) mobilization of dendritic cells (DCs)
Immune reconstitution
Monoclonal antibody (MoAb) therapy
Monoclonal antibody (mAb) treatment in a murine model
Treatment with daclizumab
Use of CD52 monoclonal antibodies (MoAbs) to prevent GVHD
Visilizumab treatment of steroid-refractory acute GVHD

GRAFT VS. TUMOR INDUCTION
Donor leukocyte infusion (May 1999), (June 1999)

HAIRY CELL LEUKEMIA
Efficacy of the anti-CD22 recombinant immunotoxin BL22

HEMATOLOGIC MALIGNANCIES
Bortezomib plus doxorubicin: Phase I combination study
Immune recognition of myeloma cells
In vivo CAMPATH-1H for graft-versus-host disease (GVHD) prevention

HEPATOCELLULAR CARCINOMA
Adoptive immunotherapy
Erlotinib therapy
Escape from immune surveillance
Incidence of chronic hepatitis C virus
Interferon therapy and chronic HCV patients: reduced risk

HER-2/NEU GENE
Anti-HER-2/neu treatments
Immune Antitumor Response

HER2-TARGETED THERAPY
Cardiac safety of trastuzumab (T)
Phase I study of pertuzumab


HODGKIN'S DISEASE
Bispecific molecule (H22xKi-4)
Treatment with radioimmunotherapy

IDIOPATHIC THROMBOCYTOPENIA (ITP)
Effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF)

IMATINIB MESYLATE
Combined effects with zoledronate
Molecular targeting of platelet-derived growth factor B (PDGFB)
Results in chronic myeloid leukemia (CML) patients with derivative chromosome 9 deletions

INHIBITORS OF EGFR
GW572016

INTERFERON ALFA THERAPY
Colon carcinoma
Chronic myelogenous leukemia (CML)

INTERLEUKIN 2
Direct gene transfer

LENALIDOMIDE
Efficacy in myelodysplastic syndromes (MDS)

LEUKEMIA
Adoptive immunotherapy to prevent relapse of acute leukemia
Cytotoxic T lymphocytes (CTL) specific for the Wilm’s tumor gene encoded transcription factor (WT1)
CD38 ligation
Gemtuzumab zogamicin
131I-anti-CD45 antibody in acute leukemia
Immune gene therapy for chronic lymphocytic leukemia
Immunostimulation of chronic lymphocytic leukemia (CLL) B cells
Immunotherapy with ex vivo-generated cytotoxic T lymphocytes
Inhibition of Bcr-Abl tyrosine kinase
Mechanisms of resistance to the tyrosine kinase inhibitor STI571
Persistence of BCR-ABL rearrangement in chronic myeloid leukemia
Priming with granulocyte colony-stimulating factor (G-CSF) in acute myeloid leukemia (AML)
Rituximab treatment of relapsed patients with hairy cell leukemia (HCL)
T-cell depletion of bone marrow transplants
Treatment of relapsed leukemia with unrelated donor leukocyte infusions

LOW-GRADE NON-HODGKIN'S LYMPHOMA (NHL)
Treatment with anti-CD20 monoclonal antibody and CHOP chemotherapy

LUNG CANCER
NY-ESO-1 expression

LUNG CARCINOMA
Phase I study of G3139 in small-cell lung cancer (SCLC)
Predictors of sensitivity to gefitinib in advanced non-small-cell lung cancer (NSCLC)

LYMPHOID MALIGNANCIES
Alemtuzumab plus rituximab
First-line and maintenance rituximab treatment
Mechanisms of rituximab resistance

MALIGNANT GLIOMA
Iodine-131-labeled 81C6 monoclonal antibody (mAb) therapy
Nonablative allogeneic hematopoietic transplantation
Retroviral delivery of interleukin-4

MALIGNANT LYMPHOMA
Rituximab for central nervous system (CNS) lymphomas
Rituximab for relapsed Hodgkin's disease

MALIGNANT PLEURAL MESOTHELIOMA (MPM)
Intrapleural administration of interleukin-2 (IL-2)

MANTLE CELL LYMPHOMA
Bendamustine plus rituximab
Graft vs. lymphoma
in duction therapy with rituximab plus CHOP
Rituximab plus alternating chemotherapy results in durable remissions

METASTATIC BREAST CANCER
Phase III study of oral marimastat
Trastuzumab and vinorelbine as first-line therapy

METASTATIC MELANOMA
Adjuvant interferon alfa-2b
Autologous Melanoma Vaccine
Combination chemoimmunotherapy
Combination of chemotherapy with interleukin-2 (IL-2) and interferon alfa (IFNa)
Phase I study of a chimeric monoclonal antibody

MONOCLONAL ANTIBODIES
Alemtuzumab
Cetuximab in refractory colorectal cancer

MULTIPLE MYELOMA (MM)
Bortezomib therapy of relapsed and refractory MM
Bortezomib vs high-dose dexamethasone
Cytokine-based tumor cell vaccine
Dendritic cells (DC)
Effects of aminobisphosphonate on T cells
First-line lenalidomide plus high-dose dexamethasone
Idiotype (Id)-specific cytotoxic T lymphocytes
Idiotype vaccination
Immunomodulatory drugs
Interferon and Multiple Myeloma
Meta-analysis of interferon (IFN) trials
Muc-1 core protein expression
Novel agents
Nuclear factor (NF)-kB blockade
Thalidomide alone or with dexamethasone
Thalidomide and doxorubicin and deep venous thrombosis (DVT)
Therapy with attenuated measles virus
Vaccination Therapy
Vascular endothelial growth factor (VEGF) effects

MYELODYSPLASTIC SYNDROME
CC-5013 treatment of MDS-associated anemia
Thalidomide therapy

MYELOFIBROSIS WITH MYELOID METAPLASIA (MMM)
Combination thalidomide plus prednisone therapy

MYELOID LEUKEMIA
Targeted a particle radioimmunotherapy

MYLOTARG
Hepatic toxicity

NEUROBLASTOMA
Anti-G_D2 monoclonal antibody therapy

NEW AGENTS
New monoclonal antibody therapies
Novel strategies
Phase I study of lapatinib
Phase II studies of temsirolus

NON-HODGKIN'S LYMPHOMA (NHL)
Antibody-targeted chemotherapy with CMC-544
Astatine-211 (²¹¹At)-labeled rituximab (chimeric anti-CD20 monoclonal antibody)
Bispecific antibody (BsAb) therapy
CHOP followed by tositumomab/iodine-131 tositumomab
CHOP plus rituximab vs. CHOP alone
Clearing of bcl-2-positive cells with rituximab therapy
Clinical outcome after idiotype vaccination
Down-regulation of Bcl-2 by rituximab
Extended rituximab treatments in follicular lymphoma (FL)
First line rituximab (anti-CD20 monoclonal antibody therapy)
First-line therapy of low-grade NHL with rituximab
Fludarabine followed by radioimmunotherapy
Ibritumomab tiuxetan radioimmunotherapy
Ifosfamide-carboplatin-etoposide (ICE) plus rituximab (RICE)
Impact of rituximab plus CHOP
Interferon alfa consolidation
In vitro biologic response to rituximab
In vivo purging with chemotherapy and rituximab
Iodine-131-tositumomab multimodal therapy
Iodine-131 (I-131) tositumomab in previously treated patients
Long-term follow-up after radioimmunotherapy
Long-term follow-up after treatment with rituximab plus CHOP (R-CHOP)
Long-term results of rituximab plus CHOP (R-CHOP) in diffuse large B-cell lymphoma
Molecular profiling
Myelodysplasia and acute myeloid leukemia following NHL therapy
Negative adjuvant therapy trial with anti-B4-blocked ricin (Anti-B4-bR) immunotoxin
Oral CD40 ligand (CD40L) gene therapy
Phase I/II trial of epratuzumab
Phase I/II study of galiximab
Pivotal trial of Iodine I 131 tositumomab
Posttransplant lymphoproliferative disorders
R-CHOP vs. CHOP in advanced follicular lymphoma
Radioimmunotherapy (RIT) with IDEC-Y2B8
Response criteria
Rituximab (an anti-CD20 MoAb) pharmacokinetics
Rituximab in combination with CHOP
Rituximab-EPOCH salvage therapy
Rituximab plus epratuzumab
Rituximab retreatment
Rituximab treatment: a European experience
Safety profile of Zevalin®
Use of dendritic cells (DCs) to induce idiotype-specific CTLs
Vaccine induced molecular remission

NON-SMALL CELL LUNG CARCINOMA (NSCLC)
Bevacizumab plus erlotinib for non-small cell lung cancer
Bevacizumab plus carboplatin and paclitaxel
Epidermal growth factor receptor (EGFR) gene copy number and mutations and increased sensitivity to gefitinib
Erlotinib; clinical and molecular results
Gefitinib therapy of recurrent or refractory NSCLC
Identification of activating mutations that underlie responsiveness to gefitinib

OVARIAN CANCER
Phototherapy and cisplatin

p53 TUMOR SUPPRESSION FUNCTION
Effect on anti-angiogenesis therapy

PALLIATION OF TRANSPLANTATION COMPLICATIONS
Anti-B-cell antibody therapy of B-lymphoproliferative disorder (PTBCL)

PANCREATIC CANCER
Bevacizumab plus gemcitabine
Phase I trial of a tumor vaccine
Phase II study of the farnesyltransferase inhibitor R115777

Phase I and II Studies
Phase I study of cantuzumab mertansine
Phase II study of trastuzumab in gynecologic tumors

Phase I Studies of New Therapies
Cancer vaccine
Farnesyl transferase inhibitor
Oncolytic virus

PHASE I STUDY RESULTS
Novel agents

PLASMA CELL DYSCRASIA
Treatment with thalidomide

POST-TRANSPLANTATION LYMPHOPROLIFERATIVE DISEASE (PTLD)
Effectiveness of partly HLA-matched allogeneic cytotoxic lymphocytes (CTLs)

PRECLINICAL STUDIES
Fc receptor modulation of antibody cytotoxicity

PROSTATE CANCER
Antigen-loaded dendritic cells
Antigen-specific cellular immunity
Bispecific antibody therapy

PROTEASOME INHIBITOR
Molecular mechanisms of activity

Radioimmunotherapy (RIT)
^90Y ibritumomab tiuxetan vs. rituximab
Iodine-¹³¹-tagged anti-CD30 antibody treatment of refractory Hodgkin's lymphoma (HL)
Iodine-131–labeled chimeric tumor necrosis treatment
^131I tositumomab for previously untreated and relapsed non-Hodgkin’s lymphoma (NHL)
^131I tositumomab treatment of mantle cell lymphoma (MCL)
^{I 131-}tositumomab treatment of previously untreated advanced FL
^Y90-Zevalin treatment of relapsed low grade and follicular non-Hodgkin's lymphoma (NHL)
^90y-ibritumomab for relapsed B-cell NHL following high-dose chemotherapy and ASCT

RECOMBINANT HUMANIZED MONOCLONAL ANTIBODY TO VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF)
Phase I studies

RELAPSED CHRONIC MYELOGENOUS LEUKEMIA (CML)
Donor lymphocyte infusion (DLI)

RENAL CELL CARCINOMA
Activity of SU11248 in metastatic RCC
Adjuvant interferon alfa therapy
Bevacizumab plus erlotinib
Graft vs. tumor effects: a case report
Cytokine therapy
Identification of a potential immunotherapy target
Pegylated interferon alfa-2a
Tumor infiltrating lymphocytes plus recombinant IL-2

RITUXIMAB
Acquired factor VIII inhibitors
Combined with CHOP for HIV-associated non-Hodgkin's lymphoma (NHL)
Concurrent versus sequential treatment with FND chemotherapy (fludarabine, mitoxantrone, dexamethasone)
Combination with hyper-CVAD in Burkitt (BL) and Burkitt-like (BLL) leukemia/lymphoma
Complement-dependent cytotoxicity (CDC)
Indolent non-Hodgkin's lymphoma (NHL)
In combination with CHOP (R-CHOP)
Optimizing therapy for patients with low-grade non-Hodgkin's lymphoma (NHL)
Prolonged Rituximab treatment
Synergy with glucocorticoids (GCs)
Treatment for B-cell malignancies
Treatment of fludarabine-associated immune thrombocytopenia (ITP)

RITUXIMAB-REFRACTORY FOLLICULAR NON-HODGKIN'S LYMPHOMA (NHL)
Radioimmunotherapy with ibritumomab tiuxetan (Zevalin; IDEC Pharmaceuticals)

RITUXIMAB THERAPY (ANTI-CD20 CHIMERIC ANTIBODY)
Effects on B-cell chronic lymphocytic leukemia (CLL)
Efficacy in bulky NHL
Cytokine release syndrome
Infusion-related side effects
Mechanism of action via generation of superoxide radicals
Mechanism of action
Minimal residual disease (MRD) after CHOP and rituximab
Therapy of gastric extranodal marginal zone (MALT) non-Hodgkin's lymphoma
Treatment of pure red blood cell aplasia (PRCA) in 2 CLL patients

RITUXIMAB WITH CHEMOTHERAPY AND AS A SINGLE AGENT
Rituximab-CHOP (R-CHOP) in patients with diffuse large B-cell lymphoma (DLBCL)
R-CHOP for follicular lymphoma
R-CVP in follicular lymphoma
Rituximab (R) plus fludarabine combination therapy of untreated chronic lymphocytic leukemia (CLL)
Maintenance therapy vs. retreatment with rituximab (R) for patients with indolent non-Hodgkin's lymphoma (NHL)
R-CHOP chemotherapy of mantle-cell lymphoma

T-CELL PROLYMPHOCYTIC LEUKEMIA (T-PILL)
High remission rate with CAMPATH-1H

THERAPY FOR RELAPSED/REFRACTORY NON-HODGKIN'S LYMPHOMA (NHL)
Extended rituximab therapy
Rituximab (a chimeric anti-CD20 monoclonal antibody) therapy)
Myeloablative 131 l-anti-CD20 antibody therapy
131 l- LYM-1 dose finding study
CAMPATH-1H (a human anti-CD52 monoclonal antibody) therapy
Radioimmunoconjugate therapy

TRANSPLANTATION
Effects of 131 l-anti-CD45 antibody in murine transplant models
HLA-mismatched hematopoietic stem cell transplantation

TUMOR ANTIGEN IDENTIFICATION
TRASTUZUMAB
Assessment of cardiac dysfunction
First-line therapy for metastatic breast cancer
In combination with ZD1839
Lethality-based selection of recombinant genes

TUMOR CELL VACCINATION
Cellular immune response mechanisms
Enhancement of graft-versus-tumor (GVT) activity

TUMOR NECROSIS FACTOR-RELATED APOPTOSIS-INDUCING LIGAND (TRAIL)
Preclinical studies

TUMOR-SPECIFIC ANTIGENS
Human myeloma cells

TYROSINE KINASE INHIBITION
Gefitinib in malignant mesothelioma
STI571 early clinical trials
Mechanisms of resistance

VACCINE THERAPY
Anti-idiotype vaccine for melanoma
Chronic myelogenous leukemia
muc1 tumor antigen
Renal cell carcinoma
Use in patients with mantle-cell lymphoma (MCL)
Vaccination with autologous melanoma cells
Vaccination with autologous tumor-derived heat-shock protein gp96

Waldenstrom’s Macroglobulinemia (WM)
Rituximab treatment

Targeted Therapies *Timely Information for Practicing Hematologists and Oncologists*
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