Background: Mantle cell lymphoma (MCL) is an aggressive and rare form of B-cell non-Hodgkin's (NHL) lymphoma and accounts for 5-10 % of adult-onset NHL in western countries (Lynch 2023). Incidence of MCL has increased since the 2000s with an age-adjusted incidence of MCL in the U.S (2015-2019) of 0.83 per 100,000 person-years (SEER*Stat 2022). MCL tends to be diagnosed at advanced stages, and the prognosis is typically poor with a reported median overall survival between 2.5 and 3.6 years (Hoster 2014). Chemoimmunotherapy regimens are the established first-line treatment (tx) for MCL patients (Zelenetz 2021). Clinical trials have demonstrated that targeted therapies including BTKis and other novel agents have clinical efficacy in relapsed/refractory MCL (Thomas 2024), however, as the tx landscape evolves and new therapies are approved or under development, the need for real-world (RW) evidence on current MCL tx patterns and safety profiles is critical for optimizing tx for this challenging hematologic malignancy.

Objectives: To describe clinical characteristics, contemporaneous treatment patterns and safety profiles among adult patients diagnosed with MCL in real-world settings.

Methods: A retrospective cohort of adult patients diagnosed with MCL between 1/1/2013 and 12/31/2023 was created in Optum Market Clarity®, which contains de-identified patient data from medical and pharmacy claims with linked electronic health record (EHR) data. Patients were eligible if they had at least 1 inpatient diagnosis (dx) or 2 outpatient dxs ≥30 days apart for MCL (ICD-10 C83.1x or ICD-9 200.4x), ≥ 180 days of continuous health plan enrollment prior to the MCL dx, no prior malignancies other than non-melanoma skin cancer, and no prior MCL-related tx. MCL-related txs based on 2024 NCCN guidelines were assessed from tx initiation to end of follow-up. Antineoplastic agents initiated within a 45-day window comprised the first line of therapy (LoT1). Subsequent lines were defined by the initiation of a new agent after the regimen definition period, a gap of > 90 days before reinitiating the same regimen, or the initiation of CAR T-cell therapy. Initiation or continuation of rituximab monotherapy up to 365 days after the regimen definition period did not generate a new line of therapy. Adverse events were identified using ICD codes from tx initiation until the occurrence of the event of interest or censoring.

Results: The study population included 1,936 newly treated MCL patients with a median follow-up of 28 months. Patients were predominantly male (71%) and Caucasian (81%), with median age at tx initiation of 67 years. At baseline, 23% had a median NCI Comorbidity Index > 2, with diabetes mellitus (25%), chronic pulmonary disease (16%), peripheral vascular disease (11%), renal disease (11%) and congestive heart failure (9%) representing the most common individual NCI comorbidities. Median days from dx to tx initiation was 42. Overall, the majority of patients were treated with Rituximab-based regimens (89%), followed by BTKi-based regimens (29%). Venetoclax-based regimen and CAR T-cell therapy uptake was low (6% and 2% of the patient cohort respectively). Among patients in LoT1 (n=1,936), 85% were treated with Rituximab-based regimens. Of these, 52% were treated with Bendamustine + Rituximab (BR), 17% were treated with Rituximab monotherapy and 12% were treated with RCHOP. BTKi were used among 12% patients in LoT1. Median duration of LoT1 was 127 days and 50% patients moved to a second line of therapy (LoT2) with a median time to next tx (TTNT) of 270 days (IQR: 158, 479). Median duration of LoT2 was 134 days, Rituximab-based regimens (61%) remained the most common therapy, and 37% patients moved from LoT2 to a third LoT with a median TTNT of 237 days. Overall, following tx initiation, 66%, 56%, 45% and 47% of patients newly developed any infection, anemia, thrombocytopenia, and neutropenia, respectively. Incident cardiovascular events, such as hypertension (39%), major bleeding (27%), cardiac failure (18%) and atrial fibrillation (15%) were also observed post tx initiation.

Conclusion: This study leveraged RW data to assess the current MCL tx landscape and safety profiles of existing therapies. Given the limited clinical effectiveness and suboptimal safety outcomes of current tx options, development of novel therapies, alone or in combination, remain an urgent priority for patients with this aggressive disease.

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2025
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