Real-World Characteristics, Treatment Patterns, and Outcomes of Patients with Mantle Cell Lymphoma By LOT
Authors: Sineshaw Helmneh M. , Bai Claire , De Nigris Enrico , Prescott Jennifer , Ogbu Uzor C. , Zettler Christina M. , Fernandes Laura L. , Wang Ching-Kun 
Published: December 2024

Introduction: Mantle Cell Lymphoma (MCL) is a rare malignancy accounting for about 3% of all non-Hodgkin lymphomas in the United States. Patients (pts) with aggressive MCL typically receive chemoimmunotherapy (CIT) with or without stem cell transplant (SCT) or recently approved therapies, such as Bruton's tyrosine kinase-inhibitors (BTKis, such as acalabrutinib approved in 2017) or chimeric antigen receptor T-cell therapy (CAR-T, such as brexucabtagene autoleucel approved in 2020). In light of recent approvals of new therapies, there is a need to explore contemporaneous, real-world (rw) pt characteristics, treatment (tx) patterns, and outcomes in MCL by line of therapy (LOT).
Methods: We used the COTA rw database to identify eligible pts. Eligible pts were aged ≥ 18 years at dx with stage I-IV MCL on or after 1/1/2012 who had initiated first-line (1L) tx. Pts were ineligible if they had concurrent primary malignancies at the time of dx, prior dx of a hematologic malignancy, clinical trial participation during MCL tx, or missing or imprecise (i.e., year-only) key study dates. The index date was the date of relevant LOT start, and the observation period was the duration of time from index to date of death or last visit. Characteristics and tx patterns were summarized using means, medians, and/or counts and percentages. SCT eligibility (based on lab values, comorbidities, and other relevant variables) was derived using available data. The following rw time to event outcomes were evaluated using the Kaplan-Meier method: time to tx discontinuation (rwTTD), time to next tx (rwTTNT), duration of response (rwDOR), progression-free survival (rwPFS), and overall survival (rwOS). Rw overall response rate (rwORR) was calculated as the proportion of pts who achieved a complete or partial response during the course of a single LOT. The Hougaard copula model was used to determine the association (τ) between rwPFS and rwOS using the Weibull margin distribution.
Results: Of 499 eligible and 1L treated pts, 173 (34.7%) proceeded to receive 2L, of which 72 (41.6% of 2L treated) went on to receive 3L, and 29 (40.3% of 3L treated) received 4L or later LOTs. The majority of pts were 50 years or older (94.8%), male (71.5%), and White (74.9%). Almost two-thirds (58.7%) of pts were treated in a community setting, and most were diagnosed with Stage III (14.0%) or IV disease (77.2%). Among patients with known TP53 mutation status (N=162), 74.7% had wild-type TP53, and 25.3% had TP53 mutation. Among patients with known TP53 expression status (N=90), similarly 74.4% were negative for TP53 expression, and about one-quarter were positive for TP53 expression.
The most common 1L tx regimens were bendamustine + rituximab (BR) with (12.6%) or without (23.0%) R maintenance therapy. Fifty (10.0%) pts received autologous SCT in 1L, although 347 pts (69.5%) were eligible based on derived eligibility. Twenty-six 2L pts received a BTKi in 1L, and 36 3L pts were exposed to a BTKi in 1L or 2L. The LOT in which the greatest proportion of pts received BTKi monotherapies was 2L (acalabrutinib: 13.9%; ibrutinib: 12.1%). Seven percent of pts in 3L received CAR-T therapy. Premature tx discontinuation was higher in later LOT, ranging from about 35% in 2L to over 41% in 4L+, and median rwTTD from 1L, 2L, 3L, and 4L initiation was 5.4, 5.6, 2.6, and 2.6 months, respectively.
Median rwTTNT from 1L, 2L, 3L, and 4L initiation was 36.8, 16.3, 6.7, and 3.2 months, respectively. rwORR to 1L, 2L, and 3L therapy was 90.4%, 67.6%, and 59.7% with median rwDOR of 40.2, 21.4, and 15.5 months among the 1L, 2L, and 3L cohorts, respectively. Median rwPFS from 1L, 2L, 3L, and 4L initiation was 33.8, 14.1, 4.0, and 2.6 months, respectively. Finally, median rwOS from 1L, 2L, and 3L initiation was 86.2 (95% CI: 80.3, 103.6), 51.7 (95% CI: 35.3, Not Reached), and 19.2 months (95% CI: 11.2, 41.1), respectively. Median rwOS among patients who had prior BTKi exposure was 35.7 months from the LOT initiated following first BTKi exposure. There was evidence of medium to strong association between rwPFS and rwOS across LOTs (τ ranging from 0.44 (95% CI: 0.25, 0.63) in 4L+ to 0.60 (95% CI: 0.54, 0.67) in 2L).
Conclusions: Patients with MCL lack clear standard treatment regimens across LOTs. Outcomes of pts with MCL who received 2L+ tx remain poor despite the recent approvals of novel therapies, demonstrating continued unmet need for this population.