Are we closer to a standard of care for Richter’s syndrome? Novel treatments on the horizon

ABSTRACT

Introduction

The therapeutic landscape for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has significantly evolved over the past decade with dramatically improved outcomes with the introduction of targeted therapies. This unfortunately has not been the case for Richter transformation (RT), the histologic transformation to a more aggressive lymphoma, most typically diffuse large B-cell lymphoma (DLBCL). As such, RT continues to be one of the most challenging complications of CLL/SLL. Historically, RT has a poor response to treatment, with a minority reaching complete remission (CR) and overall survival (OS) being less than a year.

Areas covered

The focus of this review is to discuss the effectiveness of commonly used regimens, and review existing data for emerging regimens being examined in ongoing clinical trials to improve prognosis and outcomes in patients with RT. Despite extensive efforts to optimize therapies for RT, there is still no generalized consensus on either first-line treatment regimens or regimens in the relapsed/refractory setting. RT continues to carry a high mortality rate without durable response to current therapeutic agents.

Expert opinion

Ongoing and future research may identify novel treatment approaches that will eventually improve outcomes for patients with RT. The optimal care for RT patients is a clinical trial, when feasible.

KEYWORDS:

• Richter transformation
• Richter syndrome
• chronic lymphocytic leukemia
• small lymphocytic lymphoma
• Richter’s transformation

Article highlights

• RT continues to be one of the most challenging complications of CLL/SLL, with poor responses to therapy and median OS under a year.

• Early trials combining venetoclax with chemoimmunotherapy have led to promising results in frontline therapy of RT.

• Combination studies of BTK inhibitors with immunotherapy have proven efficacious in both frontline and relapsed/refractory trials.

• Encouraging efficacy has also been noted in trials including primarily relapsed/refractory RT using pirtobrutinib and bispecific antibodies.

• The optimal therapy for an RT patient is treatment on a clinical trial, when feasible.

Declaration of interest

CC Coombs has received honoraria/served as a consultant for AbbVie, Allogene, AstraZeneca, Beigene, Genentech, Janssen, LOXO/Lilly, MEI Pharma, Mingsight, Octapharma, TG Therapeutics, has served on the speaker’s bureau for AbbVie, AstraZeneca, Beigene, Genentech, and has received research funding (paid to institution) from AbbVie, LOXO/Lilly. SM O’Brien has served as a consultant and/or received research support from AbbVie, AstraZeneca, Autolus, Beigene, Bristol Myers Squibb, Caribou Biosciences, Inc., Eli Lilly and Company, Gilead, GlaxoSmithKline, Janssen Oncology, Johnson and Johnson, Kite, Loxo Oncology, Inc., Merck, Mustang Bio, Nurix Therapeutics, Inc., Pfizer, Pharmacyclics, Regeneron, TG Therapeutics, and Vaniam Group LLC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.