Ofatumumab (OFA) Maintenance Prolongs PFS in Relapsed CLL: Prolong Study Interim Analysis Results

Background: Despite encouraging progress in treatment results, CLL remains incurable and patients (pts) eventually relapse. Currently, the effects of maintenance therapy are unknown for CLL. OFA, a human anti-CD20 monoclonal antibody, has proven efficacy as a monotherapy in refractory CLL. PROLONG is an open-label, two-arm randomized study of OFA versus observation (obs) for pts in remission after induction treatment for relapsed CLL. Here, we report interim analysis results for the key primary and secondary endpoints of the study.

Methods: Pts in CR or PR after 2^nd or 3^rd line treatment for CLL were randomized 1:1 to receive OFA (300 mg followed 1 week later by 1000 mg every 8 weeks for up to 2 years) or observation. Pts on OFA received premedication with acetaminophen, antihistamine and glucocorticoid. Pts were stratified by number and type of prior therapy, and remission status (CR or PR) after induction treatment. The primary endpoint was progression free survival (PFS) from randomization as assessed by investigator. The predefined interim analysis of efficacy occurred at 2/3 study events (minimum 187), with a p<0.001 required for a positive analysis. The interim analysis was reviewed by an Independent Data Monitoring Committee. Secondary endpoints included duration of response, OS, and safety.

Results: 474 pts were randomized prior to the interim analysis. Baseline characteristics were similar between arms (Table 1). The median duration of OFA treatment was 12.5 months. The median follow-up was 26.1 months for OFA and 24.0 months for obs. The median PFS was 28.6 months for OFA and 15.2 months for obs (HR=0.48; p<0.0001) (Figure 1). Time to start of next therapy was significantly longer in the OFA arm compared to the obs arm (median 38.0 vs. 27.4 months, HR=0.63; p=0.0076). At this time, there is no differences in OS (HR=0.92, p=0.74).

Adverse events (AEs) during the study occurred in 87% OFA pts vs. 75% obs pts. OFA pts had 25% Grade 3-4 AEs vs. 17% obs pts. Grade3-4 infections were 18% OFA vs. 13% obs. The most common (>5% of all pts) grade 3-4 AEs that occurred were neutropenia (22% OFA vs. 9% obs) and pneumonia (7% OFA vs. 4% obs). Death rate was similar in both arms (14%). AEs that lead to permanent discontinuation of treatment occurred in 8% OFA pts.

Conclusions: OFA maintenance provided significant clinical benefit for pts with relapsed CLL. OFA was well-tolerated with no unexpected toxicities. Additional data analyses are ongoing and efficacy outcomes according to patient subgroups will be presented.

Acknowledgments: The authors thank the patients for their participation in the study, the other PROLONG investigators, and the HOVON Committee.

Figure 1

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Figure 1

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Graph of PFS OFA vs. obs

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Graph of PFS OFA vs. obs

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