Characteristics and Outcome of Patients with Chronic Lymphocytic Leukaemia and Partial Response to Venetoclax-Obinutuzumab

Background

Patients with chronic lymphocytic leukaemia (CLL) who present a partial response (PR) to chemoimmunotherapy have a poorer prognosis than patients with complete response (CR). The CLL14 trial previously demonstrated significant improvement of progression-free survival (PFS) with a fixed duration regimen of venetoclax-obinutuzumab (VenG) as compared to chemoimmunotherapy with chlorambucil-obinutuzumab (ClbG) in patients with previously untreated CLL and coexisting conditions. Overall, approximately 50% of patients showed a complete response to VenG at end of treatment and 35% showed a partial response.

The aim of this report is to outline the characteristics and outcome of patients who present a PR to fixed-duration venetoclax-obinutuzumab in contrast to patients with a CR.

Methods

Patients with previously untreated chronic lymphocytic leukaemia and coexisting conditions were randomized 1:1 to receive 12 cycles of venetoclax with 6 cycles of obinutuzumab or 12 cycles of chlorambucil with 6 cycles of obinutuzumab. The primary endpoint was investigator-assessed PFS. Overall response rate and rate of complete responses as well as rates of minimal residual disease (in peripheral blood and bone marrow, via flow cytometry, ASO PCR and next generation sequencing) were key secondary endpoints. Response was assessed according to iwCLL guidelines of 2018.

Results

Total number of enrolled patients was 432. Median follow-up was 39.6 months (interquartile range 36.8 – 43.0). Among the 216 patients who were randomly assigned to receive VenG, 99 (45.8%) had a CR, 7 (3.2%) a CR with incomplete bone marrow recovery (CRi), 78 (36.1%) a PR and 9 (4.2%) stable disease at end of treatment (Figure 1A). Among 67 patients with PR and uMRD, in 37 (55.2%), response was assessed as PR due to residual lymphadenopathy >15 mm and < 72 mm (21 patients >15 mm and ≤ 20mm; 16 patients > 20mm and < 72mm) (Table 1). In 18 patients (26.9%), no bone marrow biopsy had been performed and due to the missing result, no CR was allowed to be reported in accordance with iwCLL guidelines.

Of those patients who had a complete response at end of treatment, 90 patients had uMRD levels in PB, 13 patients were MRD positive (including 5 patients with non-evaluable MRD). Sixty-seven patients had a partial response and uMRD, 9 patients had PR and were MRD positive. Patients with uMRD levels and PR had a similar PFS as patients with uMRD and CR (Figure 1B). Moreover, patients with uMRD and PR had a longer PFS than patients with detectable MRD and CR.

Conclusion

This analysis shows that 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.