Survival Outcomes Among Patients With Mantle Cell Lymphoma Treated With Bruton Tyrosine Kinase Inhibitors

A population-based cohort analysis on patients who were diagnosed with mantle cell lymphoma (MCL) found that overall survival and lymphoma-specific survival may improve with Bruton tyrosine kinase (BTK) inhibitors  when used as a second-line treatment (Blood Adv. 2022; bloodadvances.2021006934.doi:10.1182/bloodadvances.2021006934).

Ibrutinib, acalabrutinib, and zanubrutinib BTK inhibitors were approved for second-line use in MCL in 2013, 2017, and 2019, respectively. BTK inhibitors  provide a well-tolerated chemotherapy-free option for patients with advanced age and high-risk features.

“In this population-based study, we evaluated survival outcomes prior to and after the approval of ibrutinib, and hypothesized that survival benefit observed early after approval would be greatest in older patients not typically candidates for consolidative transplantation in the first-line setting,” wrote Mengyang Di, MD, PhD, Department of Hematology/Oncology, Yale University School of Medicine, New Haven, CT, and colleagues. 

Data on patients diagnosed with MCL between the years 2007-2018 was extracted from the Surveillance, Epidemiology, and End Results database. Authors followed the selected patients to the end of 2018 or death, whichever came first.

A diagnosis between the years of 2007 and 2011 placed a patient in the pre-BTK inhibitor era, while a diagnosis between the years 2014 and 2018 meant that a patient was in the BTK inhibitor era. Patients were divided based on age at diagnosis: less than 60 years, 60-69 years, 70-79 years, and 80 years or older. 

All-cause mortality and mortality from MCL were observed. All-cause mortality was analyzed through a multivariable Cox proportional hazards regression model, and was adjusted for age, sex, race, stage, and median household income at census level.  

Authors identified 3,424 patients who were diagnosed with MCL between 2007 and 2011, and 4,201 patients who were diagnosed between 2014 and 2018. Among the 7,625 total participants, 71% were male, 90% were male and white, and 49% of patients were aged 70 years or older. The median follow-up was 9.2 years for patients diagnosed with MCL between 2007 and 2011, and 2.4 years for those diagnosed between 2014 and 2018. 

Among all participants, the 3-year all-cause mortality rate was 39.8%, and the 3-year mortality from MCL rate was 27.3%, both presenting an increase as age increased. 

“The 3-year all-cause mortality was lower in the BTK iinhibitor era among all age groups, except patients [aged] <60 years old, and the 3-year MFM was lower in the BTK inhibitor era among all age groups,” wrote Dr Di and colleagues, adding, “The numeric difference of 3-year outcomes was more substantial in patients aged 70-79 for both all-cause mortality (pre-BTK inhibitor  era: 47.8%, BTK inhibitor era: 40.4%) and mortality from MCL (pre-BTK inhibitor era: 33.9%, BTK inhibitor era: 27.5%).”

Results from the multivariable analysis revealed that the risk of death was significantly lower during the BTK inhibitor era in those aged 60-69 years (HR:0.85, 95% CI: 0.72-1.00) and 70-79 years(HR: 0.80, 95% CI: 0.70-0.92), and that mortality from MCL was significantly lower during the BTK inhibitor era in these two age groups (60-69: sHR: 0.78; 70-79: sHR: 0.76).

“In this large population-based cohort analysis of individuals diagnosed with MCL, overall and lymphoma-specific survival improved in the BTKi era,” concluded Dr Di and colleagues, adding, “At a median follow up of 2.4 years in our BTKi cohort, significant survival benefits were observed in those older than 60 but less than 80 years of age, and the observed benefits were greatest in the 70-79 age group.”