☆ 4.7 Review

Clinical experiences with venetoclax and other pro-apoptotic agents in lymphoid malignancies: lessons from monotherapy and chemotherapy combination

JOURNAL OF HEMATOLOGY & ONCOLOGY (2022)

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Article Hematology

Venetoclax plus dose-adjusted R-EPOCH for Richter syndrome

Matthew S. Davids et al.

Summary: In this study, we found that the oral Bcl-2 inhibitor venetoclax could increase the sensitivity of Richter syndrome (RS) of chronic lymphocytic leukemia (CLL) to chemoimmunotherapy and improve treatment outcomes. In a single-arm trial, the combination of venetoclax and chemotherapy resulted in a 50% complete response rate, with deeper and more durable responses compared to historical regimens. Our data suggest that further studies comparing venetoclax with chemoimmunotherapy to chemoimmunotherapy alone are warranted.

BLOOD (2022)

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Article Hematology

The impact of early discontinuation/dose modification of venetoclax on outcomes in patients with relapsed/refractory chronic lymphocytic leukemia: post-hoc analyses from the phase III MURANO study

Anthony R. Mato et al.

Summary: The phase III MURANO study shows that fixed-duration venetoclax plus rituximab (VenR) improves survival in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and has a manageable safety profile. Premature discontinuation of venetoclax is associated with suboptimal outcomes, while treatment modification does not affect efficacy. Effective toxicity control is crucial for maximizing the benefits of venetoclax treatment.

HAEMATOLOGICA (2022)

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Article Oncology

Impact of venetoclax monotherapy on the quality of life of patients with relapsed or refractory chronic lymphocytic leukemia: results from the phase 3b VENICE II trial

Tara Cochrane et al.

Summary: The study shows that venetoclax monotherapy has a positive impact on the health-related quality of life of patients with relapsed/refractory CLL, especially in terms of global health status/quality of life. No new safety signals were reported in the study.

LEUKEMIA & LYMPHOMA (2022)

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Article Oncology

Venetoclax for Children and Adolescents with Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

Amber Gibson et al.

Summary: This study retrospectively reviewed the safety and efficacy of Venetoclax in pediatric and young adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL) or lymphoma (LBL). The results showed that Venetoclax is safe and effective to use in pediatric patients with ALL/LBL and should be considered in both the relapsed and upfront settings.

CANCERS (2022)

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Article Hematology

Dose-finding study of ibrutinib and venetoclax in relapsed or refractory mantle cell lymphoma

Craig A. Portell et al.

Summary: This study aimed to identify the optimal drug dosage combination for relapsed mantle cell lymphoma (MCL) patients. Among the 35 participants, the combination of VEN 200 mg and IBR 420 mg showed a high overall response rate (93.8%) and a low incidence of adverse reactions (6.2%). Higher dosage combinations did not improve treatment efficacy and were associated with higher toxicity.

BLOOD ADVANCES (2022)

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Article Hematology

Clonal hematopoiesis, myeloid disorders and BAX-mutated myelopoiesis in patients receiving venetoclax for CLL

Piers Blombery et al.

Summary: The BCL2 inhibitor venetoclax has therapeutic roles in CLL and AML and can lead to clinical and molecular abnormalities in the myeloid compartment. Mutations in the apoptosis effector BAX may result in resistance to venetoclax. Co-occurrence of BAX mutations with DNMT3A or ASXL1 mutations was observed in clonal hematopoiesis.

BLOOD (2022)

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Article Cell Biology

The BCL-2 inhibitor ABT-199/venetoclax synergizes with proteasome inhibition via transactivation of the MCL-1 antagonist NOXA

Sandra Weller et al.

Summary: The BCL-2 inhibitor ABT-199 enhances its anti-tumor effect by blocking BCL-2 and inhibiting MCL-1 through the activation of NOXA. This finding suggests the potential of combining ABT-199 with other drugs for improved cancer treatment.

CELL DEATH DISCOVERY (2022)

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Article Oncology

Targeted Venetoclax Therapy in t(11;14) Multiple Myeloma: Real World Data From Seven Hungarian Centers

Virag Reka Szita et al.

Summary: Despite the introduction of novel agents, multiple myeloma remains incurable for most patients, necessitating further therapeutic options. Venetoclax, a selective BCL-2 inhibitor, shows promising results in patients with translocation t(11;14) myeloma. In the relapsed/refractory setting, Venetoclax demonstrates a high objective response rate and median survival. High risk features such as deletion 17p or renal failure do not appear to adversely affect the efficacy of Venetoclax.

PATHOLOGY & ONCOLOGY RESEARCH (2022)

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Article Hematology

A phase 2 study of venetoclax plus R-CHOP as first-line treatment for patients with diffuse large B-cell lymphoma

Franck Morschhauser et al.

Summary: The study evaluated the efficacy and safety of venetoclax with R-CHOP in treating DLBCL, showing that adding venetoclax can increase overall response rate and PFS, particularly in the subgroup of patients with Bcl-2 protein overexpression.

BLOOD (2021)

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Article Oncology

Venetoclax Increases Intratumoral Effector T Cells and Antitumor Efficacy in Combination with Immune Checkpoint Blockade

Frederick J. Kohlhapp et al.

Summary: Venetoclax, a selective BCL2 inhibitor, can enhance the anticancer efficacy of immune checkpoint inhibitors by increasing PD-1+ T effector memory cells in mouse models. It does not impair human T-cell function and can provide a survival advantage in effector T cells, indicating its potential in combination with ICIs for cancer therapy.

CANCER DISCOVERY (2021)

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Article Hematology

Targeting BCL-2 with venetoclax and dexamethasone in patients with relapsed/refractory t(11;14) multiple myeloma

Jonathan L. Kaufman et al.

Summary: Venetoclax (Ven) is a selective small-molecule BCL-2 inhibitor that exhibits antitumoral activity against MM cells with t(11;14) translocation. The combination of Ven and dexamethasone (VenDex) showed significant efficacy and manageable safety in patients with t(11;14) positive relapsed/refractory multiple myeloma.

AMERICAN JOURNAL OF HEMATOLOGY (2021)

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Meeting Abstract Hematology

A Phase 1 Study to Evaluate the Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Lisaftoclax (APG-2575), a Novel BCL-2 Inhibitor (BCL-2i), in Patients (pts) with Certain Relapsed or Refractory (R/R) Hematologic Malignancies (HMs)

Mingyuan Sun et al.

BLOOD (2021)

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Meeting Abstract Hematology

A Phase II Study of Mini-Hyper-CVD Plus Venetoclax in Patients with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia

Sangeetha Venugopal et al.

BLOOD (2021)

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Meeting Abstract Hematology

Phase II Study of Venetoclax in Combination with Obinutuzumab and Bendamustine in Patients with High Tumor Burden Follicular Lymphoma As Front Line Therapy (PrECOG 0403)

Craig A. Portell et al.

BLOOD (2021)

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Meeting Abstract Hematology

Debulking before Initiation of Venetoclax Therapy in Untreated Patients with Chronic Lymphocytic Leukemia: Results from a Phase 3b Study

Ian W. Flinn et al.

BLOOD (2021)

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Meeting Abstract Hematology

Rituximab, Bendamustine and Cytarabine Followed By Venetoclax (V-RBAC) in High-Risk Elderly Patients with Mantle Cell Lymphoma

Carlo Visco et al.

BLOOD (2021)

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Meeting Abstract Hematology

ReVenG: A Phase 2 Study of Venetoclax Plus Obinutuzumab Retreatment in Patients with Relapsed Chronic Lymphocytic Leukemia

Matthew S. Davids et al.

BLOOD (2021)

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Meeting Abstract Hematology

Randomized Phase II/III Study of DA-EPOCH-R plus /- Venetoclax in Previously Untreated Double Hit Lymphoma: Initial Results from Alliance A051701

Jeremy S. Abramson et al.

BLOOD (2021)

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Meeting Abstract Hematology

Preliminary Safety and Efficacy Data from Patients (Pts) with Relapsed/Refractory (R/R) B-Cell Malignancies Treated with the Novel B-Cell Lymphoma 2 (BCL2) Inhibitor BGB-11417 in Monotherapy or in Combination with Zanubrutinib

Constantine S. Tam et al.

BLOOD (2021)

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Meeting Abstract Hematology

A Randomized Phase III Study of Venetoclax-Based Time-Limited Combination Treatments (RVe, GVe, GIVe) Vs Standard Chemoimmunotherapy (CIT: FCR/BR) in Frontline Chronic Lymphocytic Leukemia (CLL) of Fit Patients: First Co-Primary Endpoint Analysis of the International Intergroup GAIA (CLL13) Trial

Barbara Eichhorst et al.

BLOOD (2021)

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Meeting Abstract Hematology

Rapid and Sustained Reduction of Immunosuppressive T-Cells and Focusing of the T-Cell Repertoire in t(11;14) Relapsed/Refractory Multiple Myeloma Patients Treated with Venetoclax in Combination with Daratumumab and Dexamethasone

Nizar J. Bahlis et al.

BLOOD (2021)

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Meeting Abstract Hematology

Final Overall Survival Results from BELLINI, a Phase 3 Study of Venetoclax or Placebo in Combination with Bortezomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma

Shaji Kumar et al.

BLOOD (2021)

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Meeting Abstract Hematology

High Rates of Undetectable Minimal Residual Disease Remissions with TimeLimited Bendamustine, Rituximab, and Venetoclax (BR-VR) in Untreated Chronic Lymphocytic Leukemia (CLL)

Andrew H. Lipsky et al.

BLOOD (2021)

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Article Oncology

Safety and efficacy of navitoclax, a BCL-2 and BCL-XL inhibitor, in patients with relapsed or refractory lymphoid malignancies: results from a phase 2a study

Sven de Vos et al.

Summary: Navitoclax, a novel BCL-2 and BCL-X-L inhibitor, has shown promising antitumor activity in lymphoid tumors, but only a minority of patients demonstrated clinical activity. Adverse events mainly included thrombocytopenia and neutropenia, with some patients experiencing serious adverse events but no fatalities.

LEUKEMIA & LYMPHOMA (2021)

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Article Pharmacology & Pharmacy

Development and Characterization of Venetoclax Nanocrystals for Oral Bioavailability Enhancement

Shabari Girinath Kala et al.

Summary: Venetoclax, used in the treatment of chronic lymphocytic leukemia, has low oral bioavailability, but nanocrystals can improve its solubility and dissolution rate for better oral administration. By optimizing process parameters, nanocrystals of Venetoclax were successfully formulated, showing significant increase in saturation solubility and dissolution rate compared to the free drug.

AAPS PHARMSCITECH (2021)

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Article Hematology

Venetoclax sensitivity in multiple myeloma is associated with B-cell gene expression

Vikas A. Gupta et al.

Summary: This study found that Venetoclax sensitivity is closely associated with the expression of B-cell genes and genomic features identified in transposase-accessible chromatin sequencing, and there are potential novel biomarkers associated with Venetoclax sensitivity.

BLOOD (2021)

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Article Oncology

Venetoclax and navitoclax in Combination with Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

Vinod A. Pullarkat et al.

Summary: In this phase I study, combining venetoclax with low-dose navitoclax and chemotherapy showed good tolerability and promising efficacy in patients with relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma. Responses were observed in patients across histologic and genomic subtypes, even in those who had failed stem cell transplant therapies.

CANCER DISCOVERY (2021)

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Article Cell Biology

Venetoclax imparts distinct cell death sensitivity and adaptivity patterns in T cells

Lindsey M. Ludwig et al.

Summary: BH3 mimetics, particularly the BCL-2 specific inhibitor venetoclax (ABT-199), have shown potential as anti-cancer therapeutics and also impact the immune system, particularly T cell subsets. Short-term BCL-2 inhibition leads to changes in T cell populations towards a more memory cell state, while long-term blockade does not significantly alter T cell landscape.

CELL DEATH & DISEASE (2021)

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Article Oncology

Apoptotic Blocks in Primary Non-Hodgkin B Cell Lymphomas Identified by BH3 Profiling

Ryan N. Rys et al.

Summary: The study suggests that some non-Hodgkin lymphomas have defects in pro-apoptotic signaling, leading to enhanced anti-apoptotic ability of cells, with the presence of MCL1 protein likely being the main reason for poor response to venetoclax. Combining venetoclax with doxorubicin and vincristine may potentially improve treatment outcomes.

CANCERS (2021)

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Article Hematology

Intact TP-53 function is essential for sustaining durable responses to BH3-mimetic drugs in leukemias

Rachel Thijssen et al.

Summary: Selective targeting of BCL-2 with BH3-mimetic venetoclax has shown promising results in treating various leukemias. However, for patients with TP53 mutations, a combined BH3-mimetic approach targeting both BCL-2 and MCL-1 proves to be more effective in suppressing leukemia burden. It is crucial to use sufficiently lethal treatment strategies to maximize outcomes for patients with TP53-mutant disease and to avoid the risk of disease progression driven by emergent TP53-mutant clones.

BLOOD (2021)

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Editorial Material Hematology

How I treat chronic lymphocytic leukemia after venetoclax

Thomas E. Lew et al.

Summary: Venetoclax-based regimens have improved therapeutic options for CLL patients, achieving remissions without chemotherapy. However, long-term follow-up reveals frequent disease resistance and progression in patients with TP53 aberrations.

BLOOD (2021)

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Article Oncology

BCL2 Expression in First-Line Diffuse Large B-Cell Lymphoma Identifies a Patient Population With Poor Prognosis

Elizabeth Punnoose et al.

Summary: The expression of BCL2 in patients with DLBCL is associated with a poorer progression-free survival. The study supports the use of an IHC scoring system to select BCL2-positive patients for future research.

CLINICAL LYMPHOMA MYELOMA & LEUKEMIA (2021)

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Article Hematology

Venetoclax with dose-adjusted EPOCH-R as initial therapy for patients with aggressive B-cell lymphoma: a single-arm, multicentre, phase 1 study

Sarah C. Rutherford et al.

Summary: This study evaluated the safety and efficacy of venetoclax in combination with dose-adjusted EPOCH-R for patients with aggressive B-cell lymphomas, showing acceptable safety profile and encouraging preliminary activity at the recommended dose.

LANCET HAEMATOLOGY (2021)

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Article Oncology

Venetoclax Shows Low Therapeutic Activity in BCL2-Positive Relapsed/Refractory Peripheral T-Cell Lymphoma: A Phase 2 Study of the Fondazione Italiana Linfomi

Laura Ballotta et al.

Summary: Venetoclax monotherapy shows activity in a minority of R/R PTCL patients, but the majority of patients interrupt treatment due to disease progression. The biological characteristics of patients who may benefit from this treatment have not yet been identified.

FRONTIERS IN ONCOLOGY (2021)

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Article Oncology

Expanding the Repertoire for Large Small Molecules: Prodrug ABBV-167 Efficiently Converts to Venetoclax with Reduced Food Effect in Healthy Volunteers

Ahmed Hamed Salem et al.

Summary: Venetoclax, a BCL-2 inhibitor, has significantly transformed treatment for chronic lymphocytic leukemia and other blood-related cancers. The development of the phosphate prodrug ABBV-167 has successfully increased venetoclax's water solubility, leading to rapid conversion to the parent drug upon oral administration. These findings suggest a new approach to delivering beyond-rule-of-5 molecules to humans through solubility-enhancing prodrugs.

MOLECULAR CANCER THERAPEUTICS (2021)

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Review Hematology

BCL2 and MCL1 inhibitors for hematologic malignancies

Andrew W. Roberts et al.

Summary: BH3 mimetics are a new class of anticancer drugs that target prosurvival BCL2 proteins to induce apoptosis, with Venetoclax being the first approved BCL2 inhibitor showing activity in various lymphoid and myeloid neoplasms. Long-term exposure may lead to secondary resistance. Success of BCL2 inhibitors has led to development of BH3 mimetics targeting MCL1, with promising preclinical activity but potential challenges due to MCL1's physiological roles in nonhematologic tissues.

BLOOD (2021)

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Article Hematology

Efficacy of venetoclax plus rituximab for relapsed CLL: 5-year follow-up of continuous or limited-duration therapy

Shuo Ma et al.

Summary: The long-term follow-up of the phase 1b study of venetoclax and rituximab in patients with relapsed CLL showed durable deep responses with both continuous and limited-duration therapy. Retreatment with VenR was effective for patients experiencing disease progression after discontinuing therapy.

BLOOD (2021)

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Article Oncology

Long-term Follow-up of Patients with Relapsed or Refractory Non-Hodgkin Lymphoma Treated with Venetoclax in a Phase I, First-in-Human Study

Matthew S. Davids et al.

Summary: In this study, all patients received venetoclax monotherapy at doses of 200 to 1200 mg daily and were evaluated for ORR, PFS, DoR, and AEs. Venetoclax monotherapy was found to have a manageable safety profile and achieve durable responses in a subset of patients with FL, MCL, WM, and MZL, particularly in those who achieved CR. Further research is needed to explore combination strategies to enhance the durability of response to venetoclax.

CLINICAL CANCER RESEARCH (2021)

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Article Hematology

UNFAVORABLE GENETICS IMPACT MRD RESPONSE TO VENETOCLAX+RITUXIMAB RETREATMENT IN RELAPSED OR REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA (R/R CLL): PHASE 3 MURANO SUBSTUDY

J. Q. Wu et al.

HEMATOLOGICAL ONCOLOGY (2021)

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Article Hematology

PRELIMINARY SAFETY DATA FROM PATIENTS (PTS) WITH RELAPSED/REFRACTORY (R/R) B‐CELL MALIGNANCIES TREATED WITH THE NOVEL B‐CELL LYMPHOMA 2 (BCL2) INHIBITOR BGB‐11417

C. Y. Cheah et al.

HEMATOLOGICAL ONCOLOGY (2021)

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Meeting Abstract Oncology

First-in-human study of lisaftoclax (APG-2575), a novel BCL-2 inhibitor (BCL-2i), in patients (pts) with relapsed/refractory (R/R) CLL and other hematologic malignancies (HMs).

Sikander Ailawadhi et al.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Article Oncology

Phase I Study of Venetoclax Plus Daratumumab and Dexamethasone, With or Without Bortezomib, in Patients With Relapsed or Refractory Multiple Myeloma With and Without t(11;14)

Nizar J. Bahlis et al.

Summary: Venetoclax in combination with daratumumab and dexamethasone or bortezomib showed promising efficacy and safety in patients with multiple myeloma. Particularly effective in patients with t(11;14) translocation in RRMM.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Article Hematology

Outcomes of patients with CLL sequentially resistant to both BCL2 and BTK inhibition

Thomas E. Lew et al.

Summary: Patients with double class-resistant CLL have a poor prognosis and face high clinical challenges. They are heavily pretreated, enriched for adverse disease genetics, and have a short survival period after second-line TA therapy.

BLOOD ADVANCES (2021)

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Article Hematology

Phase 2 study of venetoclax plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma

Luciano J. Costa et al.

Summary: The study found that treatment with VenKd showed promising response rates in RRMM patients, with an overall response rate of 80% and 92% in t(11;14) patients. The median progression-free survival was 22.8 months.

BLOOD ADVANCES (2021)

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Article Oncology

Clinical Experience With Venetoclax Combined With Chemotherapy for Relapsed or Refractory T-Cell Acute Lymphoblastic Leukemia

Guillaume Richard-Carpentier et al.

CLINICAL LYMPHOMA MYELOMA & LEUKEMIA (2020)

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Article Hematology

Multiple BCL2 mutations cooccurring with Gly101Val emerge in chronic lymphocytic leukemia progression on venetoclax

Piers Blombery et al.

BLOOD (2020)

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Article Hematology

Efficacy of venetoclax in high risk relapsed mantle cell lymphoma (MCL) - outcomes and mutation profile from venetoclax resistant MCL patients

Preetesh Jain et al.

AMERICAN JOURNAL OF HEMATOLOGY (2020)

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Article Hematology

BTK inhibitor therapy is effective in patients with CLL resistant to venetoclax

Victor S. Lin et al.

BLOOD (2020)

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Article Hematology

Prognostic and predictive impact of genetic markers in patients with CLL treated with obinutuzumab and venetoclax

Eugen Tausch et al.

BLOOD (2020)

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Article Hematology

Novel BCL2 mutations in venetoclax-resistant, ibrutinib-resistant CLL patients with BTK/PLCG2 mutations

Fabienne Lucas et al.

BLOOD (2020)

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Article Hematology

Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial

Andrew H. Wei et al.

BLOOD (2020)

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Article Oncology

A randomized, open-label, Phase III study of obinutuzumab or rituximab plus CHOP in patients with previously untreated diffuse large B-Cell lymphoma: final analysis of GOYA

Laurie H. Sehn et al.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2020)

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Article Medicine, General & Internal

Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia

C. D. DiNardo et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

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Article Oncology

AZD4320, A Dual Inhibitor of Bcl-2 and Bcl-xL, Induces Tumor Regression in Hematologic Cancer Models without Dose-limiting Thrombocytopenia

Srividya B. Balachander et al.

CLINICAL CANCER RESEARCH (2020)

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Article Oncology

Venetoclax Plus Rituximab in Relapsed Chronic Lymphocytic Leukemia: 4-Year Results and Evaluation of Impact of Genomic Complexity and Gene Mutations From the MURANO Phase III Study

Arnon P. Kater et al.

JOURNAL OF CLINICAL ONCOLOGY (2020)

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Article Oncology

Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial

Othman Al-Sawaf et al.

LANCET ONCOLOGY (2020)

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Article Oncology

Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial

Shaji K. Kumar et al.

LANCET ONCOLOGY (2020)

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Article Education, Scientific Disciplines

Preventing and monitoring for tumor lysis syndrome and other toxicities of venetoclax during treatment of chronic lymphocytic leukemia

Kirsten Fischer et al.

HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM (2020)

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Article Education, Scientific Disciplines

How do we sequence therapy for marginal zone lymphomas?

Alessandro Broccoli et al.

HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM (2020)

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Meeting Abstract Hematology

Outcomes of Patients with Relapsed Mantle Cell Lymphoma Treated with Venetoclax: A Multicenter Retrospective Analysis

Yazeed Sawalha et al.

BLOOD (2020)

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Meeting Abstract Hematology

Venetoclax Re-Treatment of Chronic Lymphocytic Leukemia (CLL) Patients after a Previous Venetoclax-Based Regimen

Meghan C. Thompson et al.

BLOOD (2020)

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Meeting Abstract Hematology

Five-Year Analysis of Murano Study Demonstrates Enduring Undetectable Minimal Residual Disease (uMRD) in a Subset of Relapsed/Refractory Chronic Lymphocytic Leukemia (R/R CLL) Patients (Pts) Following Fixed-Duration Venetoclax-Rituximab (VenR) Therapy (Tx)

Arnon P. Kater et al.

BLOOD (2020)

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Meeting Abstract Hematology

Efficacy of Subsequent Novel Targeted Therapies, Including Repeated Venetoclax-Rituximab (VenR), in Patients (Pts) with Relapsed/Refractory Chronic Lymphocytic Leukemia (R/R CLL) Previously Treated with Fixed-Duration Venr in the Murano Study

Rosemary Anne Harrup et al.

BLOOD (2020)

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Meeting Abstract Hematology

Ibrutinib (Ibr) Plus Venetoclax (Ven) for First-Line Treatment of Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL): 1-Year Disease-Free Survival (DFS) Results From the MRD Cohort of the Phase 2 CAPTIVATE Study

William G. Wierda et al.

BLOOD (2020)

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Article Hematology

Undetectable peripheral blood MRD should be the goal of venetoclax in CLL, but attainment plateaus after 24 months

Thomas E. Lew et al.

BLOOD ADVANCES (2020)

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Letter Hematology

Efficacy of venetoclax monotherapy in patients with relapsed, refractory mantle cell lymphoma after Bruton tyrosine kinase inhibitor therapy

Toby A. Eyre et al.

HAEMATOLOGICA (2019)

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Article Hematology

Phase 1b study of venetoclax-obinutuzumab in previously untreated and relapsed/refractory chronic lymphocytic leukemia

Ian W. Flinn et al.

BLOOD (2019)

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Article Hematology

Venetoclax plus R- or G-CHOP in non-Hodgkin lymphoma: results from the CAVALLI phase 1b trial

Andrew D. Zelenetz et al.

BLOOD (2019)

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Review Oncology

Relapsed T Cell ALL: Current Approaches and New Directions

Christine M. McMahon et al.

CURRENT HEMATOLOGIC MALIGNANCY REPORTS (2019)

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Article Hematology

Efficacy of venetoclax in relapsed chronic lymphocytic leukemia is influenced by disease and response variables

Andrew W. Roberts et al.

BLOOD (2019)

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Editorial Material Hematology

Venetoclax resistance and acquired BCL2 mutations in chronic lymphocytic leukemia

Eugen Tausch et al.

HAEMATOLOGICA (2019)

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Article Medicine, General & Internal

Ibrutinib and Venetoclax for First-Line Treatment of CLL

Nitin Jain et al.

NEW ENGLAND JOURNAL OF MEDICINE (2019)

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Letter Hematology

Characterization of a novel venetoclax resistance mutation (BCL2 Phe104Ile) observed in follicular lymphoma

Piers Blombery et al.

BRITISH JOURNAL OF HAEMATOLOGY (2019)

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Article Hematology

SAKK 35/15: A PHASE I TRIAL OF OBINUTUZUMAB IN COMBINATION WITH VENETOCLAX IN PREVIOUSLY UNTREATED FOLLICULAR LYMPHOMA PATIENTS

A. Stathis et al.

HEMATOLOGICAL ONCOLOGY (2019)

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Article Oncology

Ibrutinib Plus Venetoclax in Relapsed/Refractory Chronic Lymphocytic Leukemia: The CLARITY Study

Peter Hillmen et al.

JOURNAL OF CLINICAL ONCOLOGY (2019)

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Article Medicine, General & Internal

Ibrutinib-Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia

T. D. Shanafelt et al.

NEW ENGLAND JOURNAL OF MEDICINE (2019)

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Article Medicine, General & Internal

Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions

K. Fischer et al.

NEW ENGLAND JOURNAL OF MEDICINE (2019)

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Article Oncology

Mitochondrial Reprogramming Underlies Resistance to BCL-2 Inhibition in Lymphoid Malignancies

Romain Guieze et al.

CANCER CELL (2019)

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Meeting Abstract Oncology

A Phase 1, First-in-Human Study of AMG 176, a Selective MCL-1 Inhibitor, in Patients With Relapsed or Refractory Multiple Myeloma

Andrew Spencer et al.

CLINICAL LYMPHOMA MYELOMA & LEUKEMIA (2019)

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Meeting Abstract Hematology

T(11;14) and High BCL2 Expression Are Predictive Biomarkers of Response to Venetoclax in Combination with Bortezomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: Biomarker Analyses from the Phase 3 Bellini Study

Simon Harrison et al.

BLOOD (2019)

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Meeting Abstract Hematology

Quantitative Analysis of Minimal Residual Disease (MRD) Shows High Rates of Undetectable MRD after Fixed-Duration Chemotherapy-Free Treatment and Serves As Surrogate Marker for Progression-Free Survival: A Prospective Analysis of the Randomized CLL14 Trial

Kirsten Fischer et al.

BLOOD (2019)

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Article Oncology

Fixed Duration of Venetoclax-Rituximab in Relapsed/Refractory Chronic Lymphocytic Leukemia Eradicates Minimal Residual Disease and Prolongs Survival: Post-Treatment Follow-Up of the MURANO Phase III Study

Arnon P. Kater et al.

JOURNAL OF CLINICAL ONCOLOGY (2019)

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Article Biochemistry & Molecular Biology

Dynamic molecular monitoring reveals that SWI-SNF mutations mediate resistance to ibrutinib plus venetoclax in mantle cell lymphoma

Rishu Agarwal et al.

NATURE MEDICINE (2019)

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Article Oncology

Acquisition of the Recurrent Gly101Val Mutation in BCL2 Confers Resistance to Venetoclax in Patients with Progressive Chronic Lymphocytic Leukemia

Piers Blombery et al.

CANCER DISCOVERY (2019)

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Article Hematology

Combination therapy incorporating Bcl-2 inhibition with Venetoclax for the treatment of refractory primary plasma cell leukemia with t (11;14)

Wilson I. Gonsalves et al.

EUROPEAN JOURNAL OF HAEMATOLOGY (2018)

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Article Hematology

Venetoclax for patients with chronic lymphocytic leukemia who progressed during or after idelalisib therapy

Steven Coutre et al.

BLOOD (2018)

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Article Oncology

Comprehensive Safety Analysis of Venetoclax Monotherapy for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia

Matthew S. Davids et al.

CLINICAL CANCER RESEARCH (2018)

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Article Oncology

Venetoclax for Patients With Chronic Lymphocytic Leukemia With 17p Deletion: Results From the Full Population of a Phase II Pivotal Trial

Stephan Stilgenbauer et al.

JOURNAL OF CLINICAL ONCOLOGY (2018)

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Article Oncology

Venetoclax for chronic lymphocytic leukaemia progressing after ibrutinib: an interim analysis of a multicentre, open-label, phase 2 trial

Jeffrey A. Jones et al.

LANCET ONCOLOGY (2018)

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Article Medicine, General & Internal

Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma

R. Schmitz et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

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Article Medicine, General & Internal

Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia

J. F. Seymour et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

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Article Medicine, General & Internal

Ibrutinib plus Venetoclax for the Treatment of Mantle-Cell Lymphoma

Constantine S. Tam et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

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Article Multidisciplinary Sciences

Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia

Carmen D. Herling et al.

NATURE COMMUNICATIONS (2018)

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Article Oncology

Venetoclax, bendamustine, and rituximab in patients with relapsed or refractory NHL: a phase 1b dose-finding study

S. de Vos et al.

ANNALS OF ONCOLOGY (2018)

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Article Oncology

Bendamustine followed by obinutuzumab and venetoclax in chronic lymphocytic leukaemia (CLL2-BAG): primary endpoint analysis of a multicentre, open-label, phase 2 trial

Paula Cramer et al.

LANCET ONCOLOGY (2018)

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Article Medicine, General & Internal

Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma

F. Morschhauser et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

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Review Oncology

BH3-Mimetic Drugs: Blazing the Trail for New Cancer Medicines

Delphine Merino et al.

CANCER CELL (2018)

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Letter Oncology

Revised Dose Ramp-Up to Mitigate the Risk of Tumor Lysis Syndrome When Initiating Venetoclax in Patients With Mantle Cell Lymphoma

Matthew S. Davids et al.

JOURNAL OF CLINICAL ONCOLOGY (2018)

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Article Hematology

A single-institution retrospective cohort study of first-line R-EPOCH chemoimmunotherapy for Richter syndrome demonstrating complex chronic lymphocytic leukaemia karyotype as an adverse prognostic factor

Kerry A. Rogers et al.

BRITISH JOURNAL OF HAEMATOLOGY (2018)

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Article Oncology

Phase I First-in-Human Study of Venetoclax in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

Matthew S. Davids et al.

JOURNAL OF CLINICAL ONCOLOGY (2017)

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Article Oncology

Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study

John F. Seymour et al.

LANCET ONCOLOGY (2017)

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Article Medicine, General & Internal

Obinutuzumab for the First-Line Treatment of Follicular Lymphoma

R. Marcus et al.

NEW ENGLAND JOURNAL OF MEDICINE (2017)

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Article Hematology

Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma

Shaji Kumar et al.

BLOOD (2017)

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Article Hematology

Promising efficacy and acceptable safety of venetoclax plus bortezomib and dexamethasone in relapsed/refractory MM

Philippe Moreau et al.

BLOOD (2017)

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Article Hematology

Clinicopathological features and outcomes of progression of CLL on the BCL2 inhibitor venetoclax

Mary Ann Anderson et al.

BLOOD (2017)

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Article Hematology

Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia

Philip A. Thompson et al.

BLOOD (2016)

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Letter Oncology

BH3 profiling identifies heterogeneous dependency on Bcl-2 family members in multiple myeloma and predicts sensitivity to BH3 mimetics

C. Touzeau et al.

LEUKEMIA (2016)

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Article Oncology

Dexamethasone treatment promotes Bcl-2 dependence in multiple myeloma resulting in sensitivity to venetoclax

S. M. Matulis et al.

LEUKEMIA (2016)

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Article Hematology

Venetoclax responses of pediatric ALL xenografts reveal sensitivity of MLL-rearranged leukemia

Seong Lin Khaw et al.

BLOOD (2016)

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Article Hematology

The BCL2 selective inhibitor venetoclax induces rapid onset apoptosis of CLL cells in patients via a TP53-independent mechanism

Mary Ann Anderson et al.

BLOOD (2016)

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Article Hematology

Transcriptome sequencing reveals a profile that corresponds to genomic variants in Waldenstrom macroglobulinemia

Zachary R. Hunter et al.

BLOOD (2016)

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Article Oncology

Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study

Stephan Stilgenbauer et al.

LANCET ONCOLOGY (2016)

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Article Oncology

Expression Profile of BCL-2, BCL-XL, and MCL-1 Predicts Pharmacological Response to the BCL-2 Selective Antagonist Venetoclax in Multiple Myeloma Models

Elizabeth A. Punnoose et al.

MOLECULAR CANCER THERAPEUTICS (2016)

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Article Medicine, General & Internal

Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia

Andrew W. Roberts et al.

NEW ENGLAND JOURNAL OF MEDICINE (2016)

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Article Biochemistry & Molecular Biology

FBXO10 deficiency and BTK activation upregulate BCL2 expression in mantle cell lymphoma

Y. Li et al.

ONCOGENE (2016)

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Review Oncology

Thirty years of BCL-2: translating cell death discoveries into novel cancer therapies

Alex R. D. Delbridge et al.

NATURE REVIEWS CANCER (2016)

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Article Hematology

Phase 1 study of the safety, pharmacokinetics, and antitumour activity of the BCL2 inhibitor navitoclax in combination with rituximab in patients with relapsed or refractory CD20+ lymphoid malignancies

Andrew W. Roberts et al.

BRITISH JOURNAL OF HAEMATOLOGY (2015)

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Article Oncology

BH3 Inhibitor Sensitivity and Bcl-2 Dependence in Primary Acute Lymphoblastic Leukemia Cells

Sarah E. Alford et al.

CANCER RESEARCH (2015)

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Article Oncology

A phase 2 study of the BH3 mimetic BCL2 inhibitor navitoclax (ABT-263) with or without rituximab, in previously untreated B-cell chronic lymphocytic leukemia

Thomas J. Kipps et al.

LEUKEMIA & LYMPHOMA (2015)

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Article Cell Biology

Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy

Joel D. Leverson et al.

SCIENCE TRANSLATIONAL MEDICINE (2015)

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Article Hematology

Poor efficacy and tolerability of R-CHOP in relapsed/refractory chronic lymphocytic leukemia and Richter transformation

Petra Langerbeins et al.

AMERICAN JOURNAL OF HEMATOLOGY (2014)

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Article Hematology

Double hit lymphoma: the MD Anderson Cancer Center clinical experience

Yasuhiro Oki et al.

BRITISH JOURNAL OF HAEMATOLOGY (2014)

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Article Hematology

Outcomes of first-line treatment for chronic lymphocytic leukemia with 17p deletion

Paolo Strati et al.

HAEMATOLOGICA (2014)

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Letter Oncology

The Bcl-2 specific BH3 mimetic ABT-199: a promising targeted therapy for t(11;14) multiple myeloma

C. Touzeau et al.

LEUKEMIA (2014)

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Article Medicine, General & Internal

Idelalisib and Rituximab in Relapsed Chronic Lymphocytic Leukemia

Richard R. Furman et al.

NEW ENGLAND JOURNAL OF MEDICINE (2014)

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Article Biochemistry & Molecular Biology

ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets

Andrew J. Souers et al.

NATURE MEDICINE (2013)

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Article Medicine, General & Internal

Targeting BTK with Ibrutinib in Relapsed Chronic Lymphocytic Leukemia

John C. Byrd et al.

NEW ENGLAND JOURNAL OF MEDICINE (2013)

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Article Oncology

Substantial Susceptibility of Chronic Lymphocytic Leukemia to BCL2 Inhibition: Results of a Phase I Study of Navitoclax in Patients With Relapsed or Refractory Disease

Andrew W. Roberts et al.

JOURNAL OF CLINICAL ONCOLOGY (2012)

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Article Hematology

Distribution of Bim determines Mcl-1 dependence or codependence with Bcl-xL/Bcl-2 in Mcl-1-expressing myeloma cells

Alejo A. Morales et al.

BLOOD (2011)

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Article Oncology

ABT-737 Induces Apoptosis in Mantle Cell Lymphoma Cells with a Bcl-2high/Mcl-1low Profile and Synergizes with Other Antineoplastic Agents

Cyrille Touzeau et al.

CLINICAL CANCER RESEARCH (2011)

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Article Oncology

Phase I Dose Finding Studies of Obatoclax (GX15-070), a Small Molecule Pan-BCL-2 Family Antagonist, in Patients with Advanced Solid Tumors or Lymphoma

Jimmy J. Hwang et al.

CLINICAL CANCER RESEARCH (2010)

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Article Oncology

Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity

Wyndham H. Wilson et al.

LANCET ONCOLOGY (2010)

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Article Hematology

Phase I study of obatoclax mesylate (GX15-070), a small molecule pan-Bcl-2 family antagonist, in patients with advanced chronic lymphocytic leukemia

Susan M. O'Brien et al.

BLOOD (2009)

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Article Oncology

Bcl-2 Inhibitors: Targeting Mitochondrial Apoptotic Pathways in Cancer Therapy

Min H. Kang et al.

CLINICAL CANCER RESEARCH (2009)

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Article Oncology

5-Year Survival in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia in a Randomized, Phase III Trial of Fludarabine Plus Cyclophosphamide With or Without Oblimersen

Susan O'Brien et al.

JOURNAL OF CLINICAL ONCOLOGY (2009)

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Article Hematology

Phase II multicenter study of oblimersen sodium, a Bcl-2 antisense oligonucleotide, in combination with rituximab in patients with recurrent B-cell non-Hodgkin lymphoma

Barbara Pro et al.

BRITISH JOURNAL OF HAEMATOLOGY (2008)

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Article Hematology

BCL-2 dependence and ABT-737 sensitivity in acute lymphoblastic leukemia

Victoria Del Gaizo Moore et al.

BLOOD (2008)

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Article Oncology

Noxa up-regulation and Mcl-1 cleavage are associated to apoptosis induction by bortezomib in multiple myeloma

Patricia Gomez-Bougie et al.

CANCER RESEARCH (2007)

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Article Biochemistry & Molecular Biology

Programmed anuclear cell death delimits platelet life span

Kylie D. Mason et al.

CELL (2007)

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Article Hematology

Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma

Wee J. Chng et al.

BLOOD (2006)

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Article Oncology

Translocation t(14;18) and gain of chromosome 18/BCL2:: effects on BCL2 expression and apoptosis in B-cell non-Hodgkin's lymphomas

E Galteland et al.

LEUKEMIA (2005)

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Article Oncology

Phase I to II multicenter study of oblimersen sodium, a Bcl-2 antisense oligonucleotide, in patients with advanced chronic lymphocytic leukemia

SM O'Brien et al.

JOURNAL OF CLINICAL ONCOLOGY (2005)

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Article Biochemistry & Molecular Biology

Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function

L Chen et al.

MOLECULAR CELL (2005)

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Review Oncology

The BCL2 family: Regulators of the cellular life-or-death switch

S Cory et al.

NATURE REVIEWS CANCER (2002)

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