, according to a recent review published in Best Practice & Research Clinical Haematology.
Use of high-dose cytarabine plus rituximab as frontline treatment is well established, with median overall survival now exceeding 10 years, said Rory McCulloch, MD, and Simon Rule, MD, of the department of Haematology, Derriford Hospital, Plymouth, England. However, there is no proven benefit to conventional therapy in patients with asymptomatic, non-bulky disease, making a watch-and-wait strategy appropriate for these patients, the authors said.
On the opposite end of the spectrum there is a subgroup of patients characterized by TP53 mutations and poor prognostic index scores that have poor outcomes in spite of conventional therapy.
These patients might have improved outcomes either with early allogeneic haematopoietic cell transplantation (allo-HCT), or, especially, clinical trials of novel agents in the upfront setting, the authors noted.
“There are a host of exciting novel agents, most prominently the BTK inhibitors, that are game changing with respect to their activity,” wrote Dr. McCulloch and Dr. Rule. “Based on the long-term results seen with conventional therapy, it is premature to be considering such new drugs in the frontline setting outside the context of a clinical trial, but it is hard to believe they will not become incorporated into treatment protocols in the future.”
Watch-and-wait treatment strategies for lower-risk patients are supported by the results of two single-center, retrospective studies published in 2009 that suggest the practice has no adverse impact on overall survival. More recent registry studies, published in 2016 and 2017, have shown that a significant proportion of patients can be managed according to the watch-and-wait strategy.
Although it’s been challenging to precisely define the group of patients for whom watch-and-wait is appropriate, enrollment criteria for studies have generally specified that patients be asymptomatic with non-bulky disease and non-blastoid morphology, they said.