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Ofatumumab maintenance extends PFS, time to next treatment in relapsed CLL
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Ofatumumab maintenance therapy prolonged PFS and time to next treatment in patients with relapsed chronic lymphocytic leukemia, according to the results of a randomized phase 3 study.
Because allogeneic hematopoietic stem cell transplantation — the only potentially curative treatment for relapsed CLL — is only feasible in a few patients, prolonged PFS and OS are often the aims of therapy in this population.
Marinus H.J. van Oers, MD, PhD, professor of hematology at Academic Medical Center in Amsterdam, and colleagues conducted the open-label, multicenter PROLONG study to assess the safety and efficacy of ofatumumab (Arzerra, Novartis) maintenance vs. observation for patients with relapsed CLL in remission following re-induction treatment.
The study included 473 adult patients in complete or partial remission after second- or third-line treatment from 130 treatment centers in 24 countries. Eligibility criteria included WHO performance status of 0 to 2, response assessment conducted within the previous 3 months and no evidence of refractory disease.
The researchers randomly assigned patients to ofatumumab (300 mg followed by 1,000 mg 1 week later, then every 8 weeks for up to 2 years; n = 237) or observation (n = 236).
PFS served as the primary endpoint. OS, time to next treatment, PFS after next-line therapy and safety served as secondary endpoints.
Median follow-up was 19.1 months (interquartile range [IQR], 10.3-28.8).
PFS appeared significantly prolonged among patients assigned ofatumumab maintenance (29.4 months vs. 15.2 months; HR = 0.5; 95% CI, 0.38-0.66).
No difference in OS occurred between the two arms (HR = 0.85; 95% CI, 0.52-1.37). However, patients assigned ofatumumab had a median longer time to next treatment (38 months vs. 31.1 months; HR = 0.66; 95% CI, 0.47-0.92).
Twenty patients in the ofatumumab arm and three patients in the observation arm permanently discontinued treatment due to adverse events. The most common grade 3 or higher adverse events included neutropenia (ofatumumab, n = 56; observation, n = 23) and infections (ofatumumab, n = 31; observation, n = 20).
Two deaths related to adverse events occurred in the ofatumumab arm, as well as five deaths in the observation arm. However, no deaths could be attributed to the study drug.
Follow-up remained ongoing at time of reporting.
“Our data of ofatumumab maintenance are very timely in the present era of novel treatment modalities,” van Oers and colleagues wrote. “Although data on long-term safety are limited, continued treatment with these kinase inhibitors until relapse is recommended. … Our data on the PFS and safety of ofatumumab maintenance treatment are important for the future discussions on the optimum maintenance strategies in relapsed CLL."
Questions persist regarding the cost and efficacy of maintenance therapy, Adrian Wiestner, MD, PhD, senior investigator in the laboratory of lymphoid malignancies at the NIH’s National Heart, Lung, and Blood Institute, wrote in an accompanying editorial.
“Whether the benefit of maintenance therapy justifies the cost, and whether maintenance therapy is superior to retreatment at the time of progression are important questions,” Wiestner wrote. “Patients in the PROLONG study were in remission at the time of enrollment, which could result in two important limitations. First, the proportion of patients having received retreatment at the participating institutions and not enrolled in PROLONG was unknown, and possible selection bias could not be readily identified. Second, because patients were in remission, baseline tumor characterization is probably incomplete. … Nevertheless, the study provides important data about the clinical benefit of ofatumumab maintenance.” – by Cameron Kelsall
Disclosure: GlaxoSmithKline and Genmab provided funding for this study. van Oers reports advisory roles with AbbVie, GlaxoSmithKline and Roche. Please see the full study for a list of all other researchers’ relevant financial disclosures. Wiestner reports grants from Acerta Pharma and Pharmacyclics.
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