Five-year follow-up of the phase III COMPLEMENT 1 study focused on the efficacy with respect to overall and progression-free survival.
CHICAGO-Five-year follow-up of the phase III COMPLEMENT 1 study showed continued efficacy with respect to overall survival (OS) and progression-free survival (PFS) of ofatumumab plus chlorambucil in chronic lymphocytic leukemia (CLL), with no new safety signals. This final analysis (abstract 7528) was presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31–June 4 in Chicago. Previously, ofatumumab combined with chlorambucil was reported to be well tolerated and to improve PFS compared with chlorambucil alone.
“There was a small improvement in overall survival, but certainly [an] improvement in progression-free survival. I think the reason that improvement in PFS didn’t translate into a more substantial benefit in overall survival is that since this study was started, many new therapies for CLL have been approved, so the patients who progressed could go on to receive any of them,” commented Catherine Diefenbach, MD, assistant professor and clinical director of lymphoma at Perlmutter Cancer Center at New York University.
Although the study results aren’t earth-shattering, they should add to the clinician’s arsenal, said Diefenbach. “I'm not sure how much play this will get given the tolerability of many of the other newer regimens, but it is nice to have another option,” she told Cancer Network.
The original study included 447 patients who were previously untreated and unfit for fludarabine-based therapy due to advanced age or comorbidities. They were randomized to ofatumumab plus chlorambucil or chlorambucil alone. During the first 28-day cycle, those in the combined treatment arm were given 300 ofatumumab on day 1 and 1,000 mg on day 8. In later cycles, they received 1,000 mg on day 1. They also received 10 mg/m2 chlorambucil on days 1 to 7. Patients underwent 3 to 12 cycles of treatment. Individuals in the chlorambucil arm received only the indicated dose of chlorambucil.
Overall, 74% of patients completed the per protocol treatment, through maximum response or up to 12 cycles. The combined arm had a median PFS of 23.4 months compared with 14.7 months in the chlorambucil arm (hazard ratio [HR], 0.61; P < .001). Median overall survival was 84.7 months for the chlorambucil arm but was not available for the combined arm. The 5-year OS rate was 68.5% in the combined arm, compared with 65.7% in the chlorambucil arm. More patients in the chlorambucil arm received post-treatment anti-cancer therapy (66% vs 56%), and they initiated anti-cancer therapy earlier (486 days vs 743 days).
Mortality was 39% in the combination arm and 44% in the chlorambucil arm. There were 5 on-treatment deaths in both groups. In total, 64% of patients in the combined group had grade 3 or higher adverse events, compared with 48% in the chlorambucil group. The most common grade ≥ 3 events were neutropenia (26% vs 15%), thrombocytopenia (5% vs 10%), pneumonia (9% vs 5%), and anemia (5% vs 5%) for the combined and chlorambucil arms, respectively.