Credit: Linda Bartlett
SAN FRANCISCO—Maintenance therapy with the anti-CD20 monoclonal antibody ofatumumab improves progression-free survival (PFS), but not overall survival (OS), in patients with relapsed chronic lymphocytic leukemia (CLL), according to an interim analysis of the PROLONG study.
The median PFS was about 29 months in patients who received ofatumumab and about 15 months for patients who did not receive maintenance (P<0.0001).
But there was no significant difference in the median OS, which was not reached in either treatment arm.
Marinus H.J. van Oers, MD, PhD, of the Academisch Medisch Centrum and HOVON in Amsterdam, The Netherlands, reported these results at the 2014 ASH Annual Meeting (abstract 21*). The study was sponsored by GlaxoSmithKline, makers of ofatumumab.
“[A]s of 2014, still we cannot say that we are able to cure CLL,” Dr van Oers noted. “And CLL is characterized by decreasing response duration with subsequent lines of treatment. In this respect, but also a number of other respects, there are similarities in biological behavior between CLL and follicular lymphoma.”
“There is definitely a role—although it’s somewhat debated—for maintenance treatment in follicular lymphoma. Therefore, it is rational to explore safe and effective maintenance treatment in CLL as well.”
To that end, Dr van Oers and his colleagues compared ofatumumab maintenance to observation in patients who were in remission after induction treatment for relapsed CLL. The team enrolled 474 patients who were in complete or partial remission after their 2nd- or 3rd-line treatment for CLL.
Patients were randomized to observation (n=236) or to receive ofatumumab (n=238) at 300 mg, followed 1 week later by 1000 mg every 8 weeks for up to 2 years. Patients on ofatumumab also received premedication with acetaminophen, antihistamine, and glucocorticoid.
The patients were stratified by the number and type of prior therapy, as well as remission status after induction treatment, and baseline characteristics were similar between the two treatment arms.
“The median age was about 65, and about 30% of patients were older than 70 years,” Dr van Oers noted. “[There was] a male preponderance, as you would expect, and the time since diagnosis was somewhere between 5 and 6 years.”
“Most patients were in [partial response], actually 80%, and most patients had received 2 prior regimens, about 70%. As for prior treatments, 80% of patients had received effective immuno-chemotherapy.”
“In both arms, there were only a few patients with unfavorable cytogenetics—11q and 17p deletion. [As for] β2 microglobulin, two-thirds [of patients in both arms] had low levels. And, in both arms, there were almost twice as many IGVH-mutated as unmutated patients.”
Patient outcomes
The median follow-up was 19.1 months. The study’s primary endpoint was PFS, which was defined as the time from randomization to the date of disease progression or death from any cause.
The median PFS was significantly longer in the ofatumumab arm than in the observation arm, at 29.4 months and 15.2 months, respectively (hazard ratio [HR]=0.50; P<0.0001).
Similarly, the time to the start of patients’ next therapy was significantly longer in the ofatumumab arm than in the in observation arm—a median of 38 months and 31.1 months, respectively (HR=0.66, P=0.108).
However, there was no significant difference in OS, which was not reached in either arm (HR=0.85, P=0.4877).
Adverse events (AEs) occurred in 86% of patients in the ofatumumab arm and 72% of patients in the observation arm (P<0.001). Sixty percent of AEs were considered related to ofatumumab. None of the AEs led to study withdrawal.
Grade 3 or higher AEs occurred in 46% of patients in the ofatumumab arm and 28% in the observation arm. They included neutropenia (24% and 10%, respectively; P<0.001), infections (13% and 8%, respectively), thrombocytopenia (2% and 3%, respectively), and infusion-related reactions (1% and 0%, respectively).
There were 5 deaths in the observation arm—1 due to progression and 4 due to causes other than progression, infection, or secondary malignancy. There were 2 deaths in the ofatumumab arm—1 due to infection/sepsis and 1 due to an “other” cause.
“So based on this planned interim analysis, we can conclude that ofatumumab maintenance in relapsed CLL results in a highly significant and clinically meaningful improvement of progression-free survival,” Dr van Oers said in closing.
“It significantly prolongs time to next treatment, it’s well-tolerated, and it’s associated with an adverse event profile which is quite characteristic of anti-CD20 monoclonal antibodies.”
*Information in the abstract differs from that presented at the meeting.