Photo Credit: David A Litman
According to data from the 66th ASH Annual Meeting, advancements in the treatment of relapsed/refractory mantle cell lymphoma (R/R MCL) have introduced novel therapies such as BTK inhibitors (BTKis). However, real-world (RW) data on treatment patterns, clinical outcomes, and racial disparities remain limited. Additionally, little is known about the outcomes of patients with TP53 mutations, a high-risk genetic feature. For this study, authors evaluated the RW clinical outcomes of chemoimmunotherapy (CIT) versusnovel therapies in patients with R/R MCL, focusing on differences by race/ethnicity and the impact of TP53 mutations.
A retrospective cohort analysis of 1,377 adult patients with R/R MCL was conducted using US Flatiron Health databases. Patients who initiated second-line (2L) or third-line (3L) therapy from 2018 onward were included. CIT comprised chemotherapy with anti-CD20 antibodies, while novel therapies included BTKis, CAR-T therapy, and other targeted treatments. RW outcomes, including median time to next treatment (mrwTTNT) and median overall survival (mrwOS), were assessed using Kaplan-Meier analysis and adjusted for age and sex.
The cohort was predominantly non-Latinx (NL)-White (75%), with smaller proportions of NL-Black (4%), Latinx (6%), NL-Asian/other (8%), and unknown/undocumented race (7%). The median age was 71 years, and 63% had progressive disease within 24 months of first-line therapy (POD24). Variations in MCL subtypes, Ki67%, and LDH levels were noted across racial groups.
First-line therapies were primarily bendamustine-rituximab (54%) and R-CHOP (18%). The most common novel therapies in 2L were acalabrutinib and ibrutinib. In 3L,novel therapies such as brexucabtagene autoleucel were increasingly used. Transplantation rates before 2L and CAR-T therapy in 3L were highest among White patients.
In 2L, mrwTTNT was longer with novel therapies (11.9 months) than CIT (9.9 months), particularly for NL-Black, NL-Asian/other, and NL-White patients. Latinx patients experienced longer mrwTTNT with CIT. Similarly, novel therapies were associated with improved mrwOS in NL-Black and NL-Asian/other patients, while CIT favored NL-White and Latinx patients. In 3L,novel therapies demonstrated improved mrwTTNT (7.9 months) and mrwOS (32.5 months) across most groups, except for Latinx patients who showed better outcomes with CIT.
Only 5% of patients were tested for TP53 mutations, with 72 patients identified as positive. These patients had poor prognoses, but novel therapies in 2L resulted in numerically longer mrwTTNT and mrwOS compared to CIT.
According to the authors, novel therapies were associated with improved mrwTTNT and mrwOS across most racial groups, except for Latinx patients who experienced greater benefit from CIT. Limited testing for TP53 mutations underscores the need for improved screening and targeted therapies for high-risk patients. Further research is essential to explore the reasons behind these disparities and optimize treatment strategies.
