What to Consider When Selecting Targeted Agents for CLL
Posted: Monday, October 25, 2021
Although treatment approaches for front-line and relapsed chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia are still informed by factors such as patient-risk profile (del17p, IGHV), comorbidities, and patient preference, the treatment landscape is now dominated by targeted therapy, according to Jennifer R. Brown, MD, PhD, Director of the CLL Center at Dana-Farber Cancer Institute, Boston. “The tolerability of targeted agents has led them to largely take over, and appropriately so,” she said in her presentation during the NCCN 2021 Virtual Congress: Hematologic Malignancies.
Patients with CLL now have options. Most patients can choose between continuous therapy with one of several Bruton’s tyrosine kinase (BTK) inhibitors (ie, ibrutinib and acalabrutinib) or 1 year of time-limited therapy with venetoclax plus an anti-CD20 antibody (typically obinutuzumab in the front-line setting and rituximab in the relapsed setting). According to Dr. Brown, early data on the novel BTK inhibitor zanubrutinib are encouraging, with an 18-month progression-free survival of more than 90% among patients with 17p deletion in the front-line setting. Many patients experience a reasonable duration of benefit with BTK inhibitors, but some do require treatment discontinuation because of adverse events. Recent data from head-to-head trials of both acalabrutinib and zanubrutinib against ibrutinib have demonstrated improved safety profiles for the next-generation drugs.
Although significant progress has been made in the field, important questions remain, commented Dr. Brown. For instance, is continuous or time-limited therapy preferred in particular categories of patients (eg, those with 17p or IGHV)? Is there a preferred agent regimen and sequence in each category? “We don’t know the answer to most of these questions as of yet, but we’re working on it,” she added.
According to Dr. Brown, another important question concerns chemoimmunotherapy. In patients with mutated IGHV, venetoclax/obinutuzumab can lead to long durations of remission off therapy, but chemoimmunotherapy also appears to be a viable option for these patients. “This is the group where chemoimmunotherapy is still most reasonable, because of the potential very long-term durability of response, or even cure, with follow-up in excess of 10 years,” she said. Follow-up is still much shorter with venetoclax/obinutuzumab, she noted.
For patients with 17p deletions, the data support the use of a continuous BTK inhibitor. However, according to Dr. Brown, these patients should also be referred for clinical trials in which multidrug combinations are being tested and measurable residual disease monitoring is conducted.
Disclosure: For full disclosures of Dr. Brown, visit nccn.org/hem.