Among patients with chronic lymphocytic leukemia (CLL) who receive chemoimmunotherapy, those with a partial response (PR) have a poorer prognosis than those with a complete response (CR). A previous study found that a fixed duration regimen of venetoclax-obinutuzumab (VenG), compared with chemoimmunotherapy with chlorambucil-obinutuzumab, in patients with previously untreated CLL and coexisting conditions significantly improved progression-free survival (PFS). At the end of treatment, about half of patients presented a CR and 35% a PR to VenG. A study that was presented at the 62nd ASH Annual Meeting & Exposition sought to determine characteristics and outcomes of patients with a PR to fixed-duration VenG compared with those with a CR.
Patients with previously untreated CLL and coexisting conditions were randomly assigned to receive 12 cycles of venetoclax with six cycles of obinutuzumab or 12 cycles of chlorambucil with six cycles of obinutuzumab. The main outcome was investigator-assessed PFS; secondary outcomes were overall response rate, CR rate, and minimal residual disease (MRD) rate.
A total of 432 patients were enrolled in the study, of whom 216 were randomized to receive VenG. Median follow-up for the entire cohort was 39.6 months (interquartile range, 36.8-43 months). In the VenG group, 99 patients had a CR (45.8%), seven had a CR with incomplete bone marrow recovery (3.2%), 78 had a PR (36.1%), and nine had stable disease at the end of treatment (4.2%). There were 67 patients with PR and undetectable MRD (uMRD); response was determined to be PR due to residual lymphadenopathy >15 mm and <72 mm (n=37), >15 mm and ≤20mm (n=21), and >20 mm and <72 mm (n=16). Eighteen patients did not undergo bone marrow biopsy, so CR could not be reported.
Among the patients with a CR at the end of treatment, 90 had uMRD levels in peripheral blood, and 13 patients were MRD positive. There were 67 patients with a PR and uMRD, and nine patients with a CR who were MRD positive. PFS was similar between patients with uMRD levels who had a PR compared with CR. PFS was longer in patients with uMRD and a PR compared with those with detectable MRD and a CR.
“This analysis shows that [the] most frequent reason for patients being staged as PR after VenG were mild residual lymphadenopathy or missing bone marrow sample. The data indicate that patients who have PR after VenG have a similar outcome as patients with CR when uMRD levels are achieved,” the study authors concluded.