STOCKHOLM – Patients with chronic lymphocytic leukemia (CLL) who experience relapse after therapy with a B-cell receptor signaling inhibitor tend to have a swiftly progressive disease course that requires immediate intervention. For these patients, a rapid venetoclax dose-escalation protocol may be a safe way to quickly regain disease control, and possibly bridge to salvage therapies, investigators reported.
Of 15 patients with CLL who relapsed after treatment with a B-cell receptor inhibitor (BCRi), all were able to get to their target dose of venetoclax under close inpatient monitoring at a median of 12 days, compared with the 35 days usually required for venetoclax dose escalation, reported Farrukh T. Awan, MD, of Ohio State University Comprehensive Cancer Center in Columbus, and his colleagues.
Only two patients developed clinical tumor lysis syndrome (TLS), a common occurrence with venetoclax therapy, and this adverse event was manageable, Dr. Awan said at the annual congress of the European Hematology Association.
“The reason why we have been doing a slow ramp up on venetoclax is the original toxicity issues that we saw early on,” he said in an interview. “But unfortunately, a lot of patients are progressing on these new agents and have very rapid disease progression, and what we have seen is that if you stop the ibrutinib, the disease progresses very quickly, and by the time they can get up to the effective dose of venetoclax, they’re too sick to continue, or they might even die from disease progression.”
Neil Osterweil/MDedge News
Dr. Farrukh T. Awan
To combat this problem, Dr. Awan and his colleagues developed a rapid dose escalation protocol that would ramp up from 20 mg to 400 mg, with increases every 1 or 2 days depending on tolerability and incident TLS. Lab tests for TLS were evaluated every 4-8 hours.
All patients were closely monitored in the hospital, and all were started on allopurinol or other uric acid–lowering agents before starting on venetoclax.
The investigators reported safety and efficacy outcomes for the patients in a retrospective analysis.
The median age of the patients, 12 men and 3 women, was 65 years (range, 58-86 years). Seven patients had Eastern Cooperative Oncology Group Performance Status of 0, seven had an ECOG score of 1, and one had a score of 2-4.
Ten patients had most recently been treated with a BCRi, either a Bruton’s tyrosine kinase inhibitor (ibrutinib or acalabrutinib), idelalisib, or entospletinib. Three patients received ibrutinib plus chemotherapy, and two received rituximab and dexamethasone followed by rituximab maintenance.
The median time to full venetoclax dose was 12 days (range, 5-21 days) and all 15 patients reached the target dose. The mean length of stay during the ramp-up period was 9.5 days (range, 6-22 days).
The incidence of clinical TLS was 13.2%, occurring in two patients, one at the initial 20-mg dose, and one at the 200-mg dose level. Another five patients had asymptomatic TLS. Other treatment-related adverse events were anemia in seven patients, neutropenia in six patients, thrombocytopenia in five patients, and lung infection in one patient.