Pharmacyclics and Johnson & Johnson’s ibrutinib has caused a stir at the American Society of Clinical Oncology meeting in Chicago, with many observers predicting that it will revolutionise treatment of chronic lymphocytic leukaemia.
Approved by the US Food and Drug Administration in February for CLL (it was also approved for mantle cell lymphoma in 2013) and marketed as Imbruvica, ibrutinib is poised to replace standard of care, particularly for elderly CLL patients who are unable to tolerate traditional chemotherapy.
“Identifying novel therapies that prolong survival is a significant need for these patients,” said John Byrd of the Ohio State University School of Medicine, making his comments before presenting the latest, and best, results so far for ibrutinib from a Phase III study at ASCO.
CLL is the most common form of adult leukaemia, and standard of care is chemotherapy followed by Rituxan (rituximab). However, elderly patients - the majority of individuals with CLL - often cannot tolerate this regimen, so for these patients the only treatment option available is GlaxoSmithKline/Genmab’s anti-CD20 antibody Arzerra (ofatumumab) which is easier to swallow, so to speak, but less effective than chemotherapy.
Enter ibrutinib. To establish the superiority of this new agent, Dr Byrd conducted a trial with 391 CLL patients comparing the first-in-class, once-daily orally-administered, covalent inhibitor of Bruton’s tyrosine kinase, versus ofatumumab.
The observed outcomes between the two treatment arms in this trial were striking. “The progression-free survival at six months was 88%,” reported Dr Byrd. “This equates to a reduction of expected deaths by 78%.”
And this reduction in mortality held up regardless of the molecular CLL subtype. In fact, the treatment was deemed so successful that at the six-month time point, ofatumumab patients were allowed to cross over to the ibrutinib treatment arm.
Post-cross over, at nine months, the rate of overall survival for the expanded ibrutinib treatment cohort demonstrated a 50% reduction in deaths that would have been otherwise observed with standard treatment. Regarding safety, Dr Byrd described the side effects as “acceptable”.
Gregory Masters of the Helen F Graham Cancer Center, and moderator of the ASCO press conference where the results were presented, was impressed. “To see an OS benefit in CLL…is really encouraging for patients with no other options. I think this drug’s efficacy may in fact transform the treatment of CLL, potentially replacing more toxic chemotherapy.”