Back in 2013, AbbVie and Johnson & Johnson’s Imbruvica got its very first FDA go-ahead, which was for previously treated mantle cell lymphoma (MCL). Now, the company is trumpeting a trial win in newly diagnosed patients despite not showing a life-extension advantage.
Adding Imbruvica on top of Teva’s chemotherapy Treanda and Roche’s Rituxan reduced the risk of disease progression or death by 25%. Detailed data from the phase 3 SHINE study are being presented at the 2022 American Society of Clinical Oncology annual meeting.
The study enrolled patients over age 65. These older patients aren’t able to receive intensive chemotherapy or stem cell transplantation because of toxicities, Michael Wang, M.D., of the University of Texas MD Anderson Cancer Center and lead investigator of the study, explained in a statement. MCL is a rare type of blood cancer, accounting for 7% of all non-Hodgkin lymphoma cases.
After a median follow-up of seven years—or 84.7 months to be exact—patients who got the Imbruvica combo went 80.6 months without disease progression, versus 52.9 months for the Treanda-Rituxan group. Patients in both groups also received Rituxan maintenance treatment after six cycles of Treanda and Rituxan.
Although a long time has gone by since the trial started, the regimen used in the control arm is highly relevant and still in use today, Craig Tendler, M.D., vice president of oncology clinical development and global medical affairs at J&J’s Janssen, said in an interview with Fierce Pharma. The more than four years of progression-free period observed in the control arm was also “quite good” compared with real-world experience, he said.
J&J has already submitted the SHINE data to the European Medicines Agency for a potential first-line nod, Tendler said. The company is also speaking with the FDA about filing with this trial, plus support of additional studies including potentially a large ongoing study with the European MCL Network in transplant-eligible patients, he added. The SHINE study was also designed to serve as the confirmatory clinical trial for Imbruvica’s original accelerated approval in second-line MCL.
But there’s one caveat.
Imbruvica didn’t show a benefit in prolonging patients’ lives. At least for now, there is no difference in overall survival between treatment arms, the trial investigators noted.
Tendler shrugged off the lack of a life extension improvement. The overall survival data are still not mature at this point, he noted. Plus, patients also received active treatment after their tumor had progressed.
Among 106 (40.5%) patients who received subsequent therapies in the control arm, 41 got a BTK inhibitor like Imbruvica as a second-line treatment. By comparison, 52 (19.9%) patients in the Imbruvica arm got subsequent treatments. “So it’s not usual or unexpected that it will take more time for survival to mature,” Tendler said.
Even without a definite survival advantage, Tendler said Imbruvica’s ability to induce durable disease control without all the symptoms and complications of disease relapse is “establishing a new benchmark” for these elderly mantle cell lymphoma patients.
Patients in both arms also reported similar quality of life. It’s a positive finding because the addition of Imbruvica didn’t seem to abrogate patients’ ability to go on about their life, Tendler said.
For Imbruvica’s existing indications as well as in the current SHINE study, the BTK inhibitor is dosed repeatedly at least until disease progression. Janssen is working to turn the drug into a fixed-duration combo with Roche and AbbVie’s Venclexta in the all-important chronic lymphocytic leukemia indication. With positive data from the phase 3 GLOW trial and phase 2 CAPTIVATE, J&J has filed that regimen with European authorities and is discussing with the FDA.