The Janssen Pharmaceutical Companies of Johnson & Johnson announced primary results from the pivotal phase 3 GLOW study (NCT03462719) evaluating fixed-duration Imbruvica plus venetoclax (I+V) compared to chlorambucil plus obinutuzumab (Clb+O) for first-line treatment of elderly or unfit patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The study demonstrated superior progression-free survival (PFS) of a once-daily, all-oral, fixed-duration regimen of I+V versus Clb+O as first-line treatment of CLL; the study also showed improved duration of remission and significantly improved depth of remission.1 With I+V, undetectable minimal residual disease (uMRD) in peripheral blood (PB) was sustained by 85 per cent of patients one year after end of treatment. The safety and tolerability profile of I+V was consistent with CLL treatments in an older population with comorbidities. These data were featured in the European Hematology Association (EHA) 2021 Virtual Press Briefing and will be presented as a late-breaking abstract during the EHA Virtual Congress (Abstract #LB1902).

"In the GLOW study, two very active blood cancer treatments are combined to create a complementary therapeutic regimen with the hope that deep responses might enable treatment-free remission for patients," said Arnon Kater†, M.D., Ph.D., deputy head of hematology, University of Amsterdam Faculty of Medicine, the Netherlands and principal study investigator. "The data from GLOW showed that Imbruvica in an oral, once-daily fixed-duration combination with venetoclax outperformed a standard chemoimmunotherapy regimen for older or unfit patients, providing the first comparative evidence that this approach has the potential to improve depth of response and, therefore, extends time to progression versus standard therapy."

The GLOW study evaluated the efficacy and safety of first-line fixed-duration I+V versus Clb+O in elderly patients with CLL/SLL, or patients ages 18-64 with a cumulative illness rating scale (CIRS) score of greater than six or creatinine clearance less than 70 mL/min. The CIRS score measures comorbidity, or concurrent non-CLL illness, in patients across multiple body systems. GLOW excluded patients with del(17p) or known TP53 mutations. Randomization to fixed-duration I+V or a standard six 28-day cycle of Clb+O was stratified by immunoglobulin heavy chain variable region gene (IgHV) mutational status and del(11q) status.1 Patients in the I+V arm received three months of Imbruvica lead-in therapy followed by 12 months of combination I+V therapy, and all patients stopped therapy regardless of MRD status. In the study, 106 patients received I+V and 105 received Clb+O (n=211; median age, 71 years).

At a median follow-up of 27.7 months, independent review committee (IRC)-assessed PFS for fixed-duration I+V was superior to Clb+O [Hazard Ratio (HR) 0.216; 95 percent confidence interval [CI], 0.131-0.357; p < 0.0001] and the improvement in PFS favoring I+V was consistent across predefined subgroups, including older patients and patients with higher comorbidity scores.1 Median PFS was not reached for I+V and 21.0 months for Clb+O (95 per cent CI, 16.6-24.7). At three months after the end of treatment (EOT+3), the rate of uMRD was significantly higher for I+V versus Clb+O in bone marrow (51.9 per cent vs. 17.1 per cent, respectively; p < 0.0001) and peripheral blood (54.7 percent versus 39.0 per cent, respectively; p < 0.0001). Complete response (CR) rates (including CR with incomplete hematologic recovery) by IRC assessment were also significantly higher for fixed-duration I+V versus Clb+O (38.7 per cent vs. 11.4 per cent; p < 0.0001).