With the initial shock of AbbVie and Johnson & Johnson's disease-specific approval pull for Imbruvica now fading into the rearview, the partners are making the case for the BTK inhibitor to stage a comeback in mantle cell lymphoma (MCL).
Used alongside AbbVie’s leukemia med Venclexta, Imbruvica helped a statistically significant number of patients with previously treated, relapsed or refractory MCL live longer without their disease getting worse versus Imbruvica alone.
The results came from a primary analysis of AbbVie’s phase 3 Sympatico study and were presented this week at the 65th American Society of Hematology annual meeting.
The data make Imbruvica’s star burn a little brighter after AbbVie and J&J in April unveiled plans to voluntarily withdraw the drug in previously treated MCL and marginal zone lymphoma (MZL). The partners decided to pull Imbruvica’s accelerated approvals after results from phase 3 confirmatory trials failed to convince the FDA of the drug's benefit, the companies said at the time.
While Imbruvica solo stumbled in MCL, the medicine could still have a future as a combination regimen, the University of Texas MD Anderson Cancer Center’s Michael Wang, M.D., an investigator on the Sympatico trial, said in a press briefing.
“In my personal opinion, this combination in the countries where ibrutinib is indicated should be a new standard therapy for relapsed/refractory mantle cell lymphoma,” Wang said during the presentation of AbbVie’s study, referring to Imbruvica by its generic name.
At the trial’s 52-month mark, Imbruvica and Venclexta helped patients live a median of 31.9 months without their disease getting worse, compared to just 22.1 months in the cohort that received Imbruvica plus placebo. After 24 months, 57% of those on the combination regimen were alive without any disease progression, compared with 45% for Imbruvica paired with a dummy medicine.
Imbruvica plus Venclexta also “significantly improved” complete response rates and patients’ time to next treatment (TTNT), Wang said in his presentation.
Despite the combo’s strong PFS performance, the jury is still out when it comes to the oncological gold standard of overall survival (OS), which proved numerically but not significantly improved at the time of AbbVie’s interim analysis.
During the presentation, there was a question as to whether a lack of significant OS benefit could blunt Wang's expectations for the Imbruvica-Venclexta combo in mantle cell lymphoma.
It’s mostly a waiting game at this point, he said, adding that the needed data for a full overall survival analysis could come by early 2025.
Ultimately, MCL is somewhat of a niche indication for Imbruvica, which mainly earns its keep thanks to an approval in chronic lymphocytic leukemia (CLL)—an indication left untouched in AbbVie’s approval purge this spring.
Between April’s approval withdrawals, the MCL pull proved more of a surprise, given that Imbruvica met the primary endpoint of the phase 3 SHINE study showing it could reduce the risk of disease progression or death in newly diagnosed MCL.
That said, the drug failed to significantly prolong patients’ lives, according to data shared at the 2022 American Society of Clinical Oncology annual meeting. At that time, Craig Tendler, M.D., vice president of oncology clinical development and global medical affairs at J&J’s Janssen, played down the lack of an overall survival showing, partly because many patients in the control arm went on to receive a BTK inhibitor following disease progression.