Venetoclax and Obinutuzumab May Benefit CLL Patients With Complex Karyotype

Patients with chronic lymphocytic leukemia (CLL) who have complex karyotype appear to have better clinical outcomes with venetoclax and obinutuzumab compared with chlorambucil and obinutuzumab, according to an analysis of the phase 3 CLL14 trial recently published in Blood.¹

The CLL14 trial (ClinicalTrials.gov Identifier: NCT02242942) previously showed that patients with CLL who received fixed-duration venetoclax and obinutuzumab had superior progression-free survival compared with chlorambucil and obinutuzumab.²

The current analysis included 397 patients, of whom 197 received chlorambucil and obinutuzumab and 200 received venetoclax and obinutuzumab. A total of 30 patients from the chlorambucil arm and 34 from the venetoclax arm had complex karyotype.

Patients with complex karyotype who received venetoclax and obinutuzumab had a similar overall response rate (ORR, 82.4% vs 87.3%; P =.42) and complete response rate (CR, 50.0% vs 51.8%; P =.85) compared with patients without complex karyotype; the overall survival (OS) was also similar (hazard ratio [HR], 1.511; 95% CI, 0.496-4.600).

In addition, among patients who received venetoclax and obinutuzumab, the rates of minimal residual disease (MRD) negativity in the peripheral blood (79.4% vs 77.1%; P =1.0) and bone marrow (58.8% vs 57.8%; P =1.0) were similar between patients with complex karyotype and patients without complex karyotype.

In contrast, patients with complex karyotype who received chlorambucil and obinutuzumab had a significantly worse ORR (50% vs 78%; P =.003), CR rate (10% vs 27.5%; P =.041), and OS (HR, 3.736; 95% CI, 1.357-10.287; P =.006) compared with patients without complex karyotype.

Also, among patients who received chlorambucil and obinutuzumab, the rates of MRD negativity in the peripheral blood (20.0% vs 40.1%; P =.041) and bone marrow (0.0% vs 22.2%; P =.002) were significantly lower for patients with complex karyotype compared with patients without complex karyotype.

“Frontline treatment with venetoclax and obinutuzumab, but not chlorambucil and obinutuzumab shows similar efficacy in patients with and without [complex karyotype],” the study authors wrote. “Thus, patients with [complex karyotype] might particularly benefit from upfront treatment with novel agents.”

References

1. Al-Sawaf O, Lilienweiss E, Bahlo J, et al. High efficacy of venetoclax plus obinutuzumab in patients with complex karyotype and chronic lymphocytic leukemia [published online January 27, 2020]. Blood. doi: 10.1182/blood.2019003451
2. Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225-2236.