Outcomes of Rituximab and Bendamustine Induction Regimen VS Cytarabine-Based Induction for Patients with Mantle Cell Lymphoma
Authors: Alnimer Yanal , Yalniz Fevzi , Monohan Gregory , Munker Reinhold , Qasrawi Ayman , Iragavarapu Chait , Amr Mahmoud 
Published: December 2024

Introduction:
Several studies have shown the superiority of cytarabine when added to anthracyclines and cyclophosphamide-based regimens, such as the Nordic regimen, in achieving remission in patients with Mantle cell lymphoma (MCL). However, no randomized control trial proved the benefit of adding Cytarabine to Bendamustine. In this single-institution study, we retrospectively evaluated overall and relapse-free survival in both cohorts.
Methods:
We retrospectively collected demographic, clinical, and outcome data on patients diagnosed with MCL at the University of Kentucky from 2009 to 2021. Data was collected in RedCaps at the University of Kentucky. We divided our cohort into three groups: Group A received a Cytarabine induction regimen without Bendamustine, Group B received a Bendamustine regimen without Cytarabine, and Group C received neither Cytarabine nor Bendamustine in their first induction. The chi-square test and t-test are used for unadjusted binary and continuous variables, respectively, and the Gehan-Breslow test was used to compare the survival curves. We used inverse probability of treatment weights (IPTW) to match the three groups on the following confounding variables: age, sex, Ki-67, the presence of blastoid or pleomorphic variants, estimated GFR (&lt;45, 45-60, &gt;60), body mass index and TP 53 mutation and Mantle Cell Lymphoma international prognostic score (MIPI) using group C as the reference group. Overall survival (OS) and relapse-free survival (RFS) were compared in the weighted data.
Results: We identified 92 patients with MCL in our institution from 2009-2023. The median age was 65.8 (IQR=58.8-71.2). The median MIPI score was 5 (IQR=3-8). 63% were males. Most patients (72%) had stage IV at diagnosis. We identified only seven patients with TP53 mutation; most patients (67%) had normal karyotypes. Thirty-eight patients (41%) received cytarabine as part of their induction regimen (Group A). In comparison, 30 (33%) received a Bendamustine-based regimen without cytarabine (Group B), and 24 patients (26%) received other upfront induction regimens (Group C). The median overall (OS) and relapse-free survival (RFS) for the total cohort was 87 months (0.95 CI 56.8-NR) and 85.5 months (0.95 CI 47-NR) respectively in the unadjusted analysis.
Group B was older than Group A (70.5 VS 58.9, Pvalue=0.003). The median MIPI score was six for group B versus four for group A (P value&lt;0.01). The median LDH was 308 in group B and 212 in group A (P value=0.18). 50% of Group A (19 patients) had consolidation with Autologous Stem Cell Transplant (ASCT), while only four patients (13%) of Group B had ASCT. Group A tends to have better OS compared to group B (Median OS NR VS 85 months (P value=0.068)) and median RFS of 104 months VS 51 months (P value of 0.049). Also, they were more likely to achieve CR following induction (38% VS 32%, P value=0.6).
Appropriate balance was achieved after matching using IPTW. After matching, the mean age was 71 VS 66 VS 65 in Groups A, B, and C respectively. The mean MIPI was 5.7 VS 6.4 VS 5.9 for Groups A, B, and C, respectively. The median OS for group A was NR (0.95 CI 59.6-NR) and 85 months for group B (0.95 CI 44.2-86.56) with a P value of 0.23. Also, the Median RFS was NR in group B (0.95 CI 44.2 -NR) VS NR for group A (0.95 CI 103-NR) with a P value of 0.163.
Conclusion: MCL patients who received Bendamustine without Cytarabine in their first induction have OS and RFS comparable to those treated with Cytarabine-based regimens. A larger study is needed to validate our findings and evaluate whether adding Cytarabine to Bendamustine could improve the outcomes among MCL patients.