Relapsed and refractory disease
With similarly high efficacy observed with the new drug classes among relapsed and/or refractory patients, chemoimmunotherapy has likewise “become obsolete in nearly all patients naive to novel agents at relapse who typically present with genetically high-risk disease,” Dr. Bohn noted.
He wrote that most of the recommendations for frontline therapy hold true in the relapsed and refractory patients, with comorbidities and personal preferences again key drivers of treatment choices.
While data is currently limited regarding benefits of venetoclax-based regimens over BTK inhibitors in relapsed/refractory patients, there is “growing evidence suggesting similar clinical outcomes achievable with these agents in either order,” Dr. Bohn wrote.
Further recommendations regarding relapsed or refractory patients include:
- Among patients who do experience disease progression while on continuous treatment with BTK inhibitors, venetoclax-based regimes seem most effective. However, with relapse after venetoclax-based regimes, some growing evidence supports retreatment with the drug “depending on depth and duration of response achieved after first venetoclax exposure,” Dr. Bohn noted.
- For patients with deletion 17p, venetoclax shows promising efficacy during relapse when given as monotherapy until disease progression or occurrence of unacceptable toxicity.
- And for patients with TP53 abnormalities, the considerations are the same as for frontline therapy, with venetoclax showing promising efficacy when given in monotherapy until disease progression or occurrence of unacceptable toxicity.
Of note, PI3K inhibitors are generally not used in CLL patients naive to BTK and BCL2 inhibitors because of the higher risk of immune-mediated toxicities and infectious complications associated with the currently approved PI3K inhibitors idelalisib and duvelisib, he reported.
Nevertheless, “PI3K inhibitors remain a valuable therapeutic addition in patients refractory or intolerant to BTK inhibitors and venetoclax-based regimens,” Dr. Bohn said.
Newer agents, fixed duration
Commenting on the review, hematologist Seema A. Bhat, MD, an assistant professor with the Ohio State University Comprehensive Cancer Center, Columbus, said that the advances with targeted therapies in CLL are paying off with improved survival.
Dr. Seema Bhat
“With these recent advances in the treatment of CLL, especially the availability of targeted therapies, there has been an improvement in survival of patients with CLL, as the CLL-related death rate steadily reduced by approximately 3% per year between 2006 and 2015,” she said in an interview.
She added that even-newer agents in development, including the reversibly binding BTK inhibitor–like pirtobrutinib and nemtabrutinib, when approved, will further add to the treatment choices for patients.
Meanwhile, a key area of focus is the combination of BTK inhibitors and BCL2 inhibitors, specifically for a fixed duration of time to obtain a deeper response and hence possibility a time-limited therapy, she noted. “We are also excited about the possibility of having more fixed-duration treatments available for our patients, which will make their treatment journey less troublesome, both physically as well as financially.”
Dr. Bohn reported receiving personal fees from AbbVie, AstraZeneca and Janssen for advisory board participation. Dr. Bhat has served on advisory board for AstraZeneca and received honorarium from them.