Successful Treatment of Richter Transformation with Ibrutinib in a Patient with Chronic Lymphocytic Leukemia following Allogeneic Hematopoietic Stem Cell Transplant

Master, Samip; Leary, Cheri; Takalkar, Amol; Coltelingam, James; Mansour, Richard; Mills, Glenn; Koshy, Nebu

doi:10.1159/000477338

Cited by 12 publications

(5 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bruton’s tyrosine kinase (BTK), a component of BCR, plays a central role in B-cell malignancies, regulating cell proliferation and survival. Ibrutinib, the first-in-class BTK inhibitor, showed activity in DLBCL-RT ( 80 – 82 ), with a survival benefit and a 16 months PFS ( 82 ). Responses to ibrutinib rechallenge have been reported after incidental RT diagnosis upon ibrutinib discontinuation in three patients with CLL ( 83 ).…”

Section: Treatment Of Dlbcl-rtmentioning

confidence: 99%

Biology and Treatment of Richter Transformation

Condoluci

Rossi

2022

Front. Oncol.

View full text Add to dashboard Cite

Richter transformation (RT), defined as the development of an aggressive lymphoma on a background of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), represents a clinical unmet need because of its dismal prognosis. An increasing body of knowledge in the field of RT is arising from the recent development of preclinical models depicting the biology underlying this aggressive disease. Consistently, new therapeutic strategies based on a genetic rationale are exploring actionable pathogenic pathways to improve the outcome of patients in this setting. In this review, we summarize the current understandings on RT biology and the available treatment options.

show abstract

Section: Treatment Of Dlbcl-rtmentioning

confidence: 99%

Biology and Treatment of Richter Transformation

Condoluci

Rossi

2022

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…In a study of four patients with RS, responses in three patients, including one CR and two partial responses (PRs), were reported [ 59 ]. Other case studies reported responses in patients with DLBCL variant RS on ibrutinib [ 60 , 61 ], with PFS of up to 16 months [ 61 ].…”

Section: Treatment Options Of the Dlbcl Variant Of Rsmentioning

confidence: 99%

Richter Syndrome

Condoluci

Rossi

2021

Curr Oncol Rep

View full text Add to dashboard Cite

Purpose of Review Richter syndrome (RS) is an uncommon but aggressive evolution of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). RS is an unmet clinical need in the field of CLL. Recent advances in understanding the biology of this condition provide the rationale for testing new therapeutic concepts in order to improve the outcome of patients developing RS, which is so far poor. In this review, we summarize disease characteristics and available therapeutic options for RS. Recent Findings Current regimens with novel agents in monotherapy have shown little impact on survival. Nevertheless, the better reported outcome for RS has been achieved with the combination of chemo-immunotherapy with a novel agent, confirming the synergistic effect of the approaches. Still, the frailty of this population may impose a less toxic management leaving most patients with no reasonable therapeutic option. Summary Treatment options for RS need to be further expanded. Preclinical models in current development may allow to explore actionable pathways and identify new drug targeted combinations.

show abstract

“…Ibrutinib, a BTK inhibitor, has shown well tolerability in small cohorts of patients but poor clinical effects with only partial responses and a complete response obtained only in one patient [76][77][78][79]. Similar limited results have been obtained also with acalabrutinib, an irreversible BTK inhibitor, that showed a good tolerability profile, but poor responses when used as monotherapy [80].…”

Section: Small Molecules-targeted Therapymentioning

confidence: 78%

Novel Approaches for the Treatment of Patients with Richter’s Syndrome

Iannello

Deaglio

Vaisitti

2022

Curr. Treat. Options in Oncol.

View full text Add to dashboard Cite

Opinion statementIn the last 10–15 years, the way to treat cancers has dramatically changed towards precision medicine approaches. These treatment options are mainly based on selective targeting against signaling pathways critical for or detrimentally activated in cancer cells in cancer cells, as well as exploiting molecules that are specifically expressed on neoplastic cells, also known as tumor-associated antigens. These considerations hold true also in the hematological field where a plethora of novel targeted agents have reached patients’ bedside, significantly improving clinical responses. Chronic lymphocytic leukemia (CLL) is an example of how targeted therapies, such as BTK, PI3K, or Bcl-2 inhibitors as well as anti-CD20 antibodies, have improved patients’ management, even when adopted as frontline treatment. However, these advancements do not apply to Richter’s syndrome (RS), the transformation of CLL into a very aggressive and fatal lymphoma, occurring in 2–10% of patients. RS is usually a fast-growing lymphoma of the diffuse large B cell or the Hodgkin’s variant, with a dismal prognosis. Despite advancements in depicting and understanding the genetic background of RS and its pathogenesis, no significant clinical results have been registered. In the last couple of years, several studies have started to investigate the impact of novel drugs or drug combinations and some of them have opened for clinical trials, currently in phase I or II, whose results will be soon available. This review will present an overview of current and most recent therapeutic options in RS, discussing also how results coming from xenograft models may help in designing and identifying novel treatment opportunities to overcome the lack of effective therapies.

show abstract

Successful Treatment of Richter Transformation with Ibrutinib in a Patient with Chronic Lymphocytic Leukemia following Allogeneic Hematopoietic Stem Cell Transplant

Cited by 12 publications

References 37 publications

Biology and Treatment of Richter Transformation

Biology and Treatment of Richter Transformation

Richter Syndrome

Novel Approaches for the Treatment of Patients with Richter’s Syndrome

Contact Info

Product

Resources

About