4.2 Review

SOHO State of the Art Updates and Next Questions | Treatment of Richter's Transformation

Related references

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Article Biochemistry & Molecular Biology

Evolutionary history of transformation from chronic lymphocytic leukemia to Richter syndrome

Erin M. Parry et al.

Summary: Richter syndrome (RS), an aggressive malignancy that arises from chronic lymphocytic leukemia (CLL), has been studied to understand its genetic mechanisms. Through computational analysis of CLL-RS whole-exome sequencing data, specific somatic driver mutations, recurrent copy-number alterations, and chromosomal abnormalities were identified in RS cells. The study also revealed distinct molecular subtypes of RS and the potential use of cell-free DNA analysis for early diagnosis and monitoring.

NATURE MEDICINE (2023)

Article Medicine, General & Internal

Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia

J. R. Brown et al.

Summary: In a multinational phase 3 trial, zanubrutinib was found to be superior to ibrutinib in treating relapsed or refractory CLL or SLL, with better efficacy and fewer side effects.

NEW ENGLAND JOURNAL OF MEDICINE (2023)

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)

Article Oncology

Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients With Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study

Lihua E. Budde et al.

Summary: This study evaluated the safety, tolerability, and efficacy of mosunetuzumab in patients with relapsed or refractory B-cell non-Hodgkin lymphomas (B-NHLs). The results showed that mosunetuzumab has a manageable safety profile and induces durable complete responses in some patients.

JOURNAL OF CLINICAL ONCOLOGY (2022)

Article Medicine, General & Internal

Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma

Herve Tilly et al.

Summary: In untreated intermediate-risk or high-risk DLBCL patients, those who received pola-R-CHP had a lower risk of disease progression, relapse, or death compared to those who received R-CHOP. Overall survival and safety profiles were similar between the two groups.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

Article Oncology

Results of ARI-0001 CART19 Cells in Patients With Chronic Lymphocytic Leukemia and Richter's Transformation

Valentin Ortiz-Maldonado et al.

Summary: This study reported the outcome of nine CLL patients treated with ARI-0001 CART19 cells, showing that this therapy is feasible, safe, and effective for high-risk CLL or RT patients.

FRONTIERS IN ONCOLOGY (2022)

Article Hematology

The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee

Elias Campo et al.

Summary: Since 1994, the classification of lymphoid neoplasms has been continuously updated through international efforts, with recent progress driven by genomic studies. This proposal presents the International Consensus Classification of mature lymphoid, histiocytic, and dendritic cell tumors, which has refined diagnostic criteria and incorporated new insights from genomics.

BLOOD (2022)

Article Hematology

The complex karyotype landscape in chronic lymphocytic leukemia allows the refinement of the risk of Richter syndrome transformation

Andrea Visentin et al.

Summary: Complex karyotype (CK) at chronic lymphocytic leukemia (CLL) diagnosis is a negative biomarker of adverse outcome. The impact of CK on the risk of developing Richter syndrome (RS) is unknown. A multicenter real-life retrospective study was conducted to test its prognostic impact. The results demonstrate that CK landscape at CLL diagnosis allows the risk of RS transformation to be refined and a prognostic model is established.

HAEMATOLOGICA (2022)

Article Oncology

Selinexor Combined with Ibrutinib Demonstrates Tolerability and Safety in Advanced B-Cell Malignancies: A Phase I Study

Deborah M. Stephens et al.

Summary: The combination of selinexor and ibrutinib has demonstrated tolerability and durable responses in patients with relapsed/refractory CLL/NHL. Notable responses were seen in patients with CLL with minimal prior therapy.

CLINICAL CANCER RESEARCH (2022)

Review Oncology

Biology and Treatment of Richter Transformation

Adalgisa Condoluci et al.

Summary: Richter transformation (RT) is an aggressive lymphoma that develops on a background of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with a poor prognosis. Recent developments in preclinical models and genetic rationale-based therapeutic strategies aim to improve patient outcomes in this setting.

FRONTIERS IN ONCOLOGY (2022)

Article Oncology

CD47xCD19 bispecific antibody triggers recruitment and activation of innate immune effector cells in a B-cell lymphoma xenograft model

Xavier Chauchet et al.

Summary: This study provides detailed mechanisms of how the CD47xCD19 bispecific antibody NI-1701 controls tumor growth in a lymphoma mouse model, including transforming the tumor microenvironment, enhancing immune effector cell responses, and facilitating dendritic cell-mediated phagocytosis. These findings suggest the potential therapeutic value of NI-1701 in the treatment of B-cell lymphoma.

EXPERIMENTAL HEMATOLOGY & ONCOLOGY (2022)

Article Oncology

A phase two study of high dose blinatumomab in Richter's syndrome

Philip A. Thompson et al.

Summary: Richter's Syndrome, a aggressive transformation of CLL, can be treated with high dose blinatumomab which shows promising efficacy in reducing lymph node disease and achieving complete response. The treatment is well-tolerated with mild side effects. Immunophenotyping reveals that patients with better treatment response have lower expression of immune checkpoints.

LEUKEMIA (2022)

Review Oncology

The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms

Rita Alaggio et al.

Summary: This article provides an overview of the upcoming 5th edition of the World Health Organization classification of lymphoid tumors, highlighting changes from the previous edition such as reorganization of entities, modification of nomenclature, revision of diagnostic criteria, deletion of entities, introduction of new entities, and inclusion of tumor-like lesions.

LEUKEMIA (2022)

Article Hematology

Real-world outcomes following venetoclax therapy in patients with chronic lymphocytic leukemia or Richter syndrome: a FILO study of the French compassionate use cohort

Florian Bouclet et al.

Summary: The BCL2 inhibitor venetoclax shows high efficacy in CLL patients, with complex karyotype identified as a predictor of inferior survival outcomes. Tumor lysis syndrome and infections were common adverse events, while venetoclax demonstrated a well-balanced safety/efficacy profile in this real-world setting.

ANNALS OF HEMATOLOGY (2021)

Article Hematology

ROR1 targeting with the antibody-drug conjugate VLS-101 is effective in Richter syndrome patient-derived xenograft mouse models

Tiziana Vaisitti et al.

Summary: The Richter syndrome (RS) is a transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, with limited treatment options and high fatality rates. Targeting the receptor tyrosine kinase-like orphan receptor 1 (ROR1) with the antibody-drug conjugate (ADC) VLS-101 has shown promising results in RS patient-derived xenografts, indicating the therapeutic potential of this approach for hematological cancers. A phase 1 clinical trial of VLS-101 (NCT03833180) is currently ongoing in patients with RS and other hematological malignancies.

BLOOD (2021)

Article Hematology

Autologous and allogeneic hematopoietic cell transplantation for diffuse large B-cell lymphoma-type Richter syndrome

Alex F. Herrera et al.

Summary: Hematopoietic cell transplantation (HCT), including autologous and allogeneic HCT, may lead to durable remissions in therapy-sensitive patients with Richter syndrome. Complete response was associated with better outcomes in the allo-HCT cohort, while cytogenetic abnormalities and prior novel therapy did not impact outcomes.

BLOOD ADVANCES (2021)

Article Hematology

Reduced-intensity conditioning hematopoietic stem cell transplantation for chronic lymphocytic leukemia and Richter's transformation

Oscar B. Lahoud et al.

Summary: This study demonstrates that allogeneic hematopoietic stem cell transplantation (HSCT) can potentially cure patients with chronic lymphocytic leukemia (CLL), with favorable progression-free survival (PFS) and overall survival (OS) rates. The impact of novel agents on HSCT outcomes was found to be negligible. Reduced intensity conditioning (RIC) HSCT may be a successful treatment option for CLL patients with Richter's transformation and poor-risk CLL patients.

BLOOD ADVANCES (2021)

Review Health Care Sciences & Services

Non-Covalent BTK Inhibitors-The New BTKids on the Block for B-Cell Malignancies

Katharine L. Lewis et al.

Summary: The B-cell receptor signalling pathway is crucial in the development of B-cell malignancies, with Bruton's tyrosine kinase (BTK) activation as a central element. While covalent BTK inhibitors have revolutionized treatment, issues such as adverse events and resistance have led to the exploration of non-covalent BTK inhibitors as an alternative therapeutic option. These non-covalent BTK inhibitors offer promise for patients intolerant to or experiencing disease progression with traditional covalent BTK inhibitors.

JOURNAL OF PERSONALIZED MEDICINE (2021)

Letter Hematology

Pembrolizumab in relapsed or refractory Richter syndrome

Philippe Armand et al.

BRITISH JOURNAL OF HAEMATOLOGY (2020)

Article Medicine, General & Internal

Transformation to plasmablastic lymphoma in CLL upon ibrutinib treatment

Kristo Marvyin et al.

BMJ CASE REPORTS (2020)

Letter Hematology

BCR kinase inhibitors, idelalisib and ibrutinib, are active and effective in Richter syndrome

Andrea Visentin et al.

BRITISH JOURNAL OF HAEMATOLOGY (2019)

Review Radiology, Nuclear Medicine & Medical Imaging

PET/Computed Tomography in Chronic Lymphocytic Leukemia and Richter Transformation

Joanna M. Rhodes et al.

PET CLINICS (2019)

Review Hematology

Biology and treatment of Richter syndrome

Davide Rossi et al.

BLOOD (2018)

Article Education, Scientific Disciplines

Richter transformation in the era of novel agents

Wei Ding

HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM (2018)

Article Medicine, Research & Experimental

Ibrutinib treatment improves T cell number and function in CLL patients

Meixiao Long et al.

JOURNAL OF CLINICAL INVESTIGATION (2017)

Meeting Abstract Oncology

Richter's syndrome (RS) in patients with chronic lymphocytic leukemia (CLL) on novel agent therapy.

Matthew Steven Davids et al.

JOURNAL OF CLINICAL ONCOLOGY (2017)

Article Medicine, General & Internal

Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia

Andrew W. Roberts et al.

NEW ENGLAND JOURNAL OF MEDICINE (2016)

Review Hematology

How we treat Richter syndrome

Sameer A. Parikh et al.

BLOOD (2014)

Article Immunology

Genetic lesions associated with chronic lymphocytic leukemia transformation to Richter syndrome

Giulia Fabbri et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2013)