Initial Treatment Patterns and Survival Outcomes of Mantle Cell Lymphoma Patients in China in the Rituximab Era

Introduction:Mantle cell lymphoma is an uncommon subtype of B-cell non-Hodgkin lymphoma with variable initial treatment strategies defined by disease risk factors, patient preferences and access to medical care. There is a paucity of reported data on treatment patterns and clinical outcomes in Chinese patient populations managed in the rituximab era. The study aim was to evaluate and compare outcome in relation to prognostic factors and first-line treatment in patients with MCL managed in real-world academic medical centers in China.

Methods:Retrospective data were collected from 5 major Chinese Hematology Centers in Beijing, Guangzhou, Nanjing, Shanghai and Suzhou from the period of 2007 to 2017. Diagnosis for MCL was based on characteristic immuno-phenotype and CyclinD1 immunohistochemistry staining. Overall Survival (OS) time was calculated from date of diagnosis to date of death or date of last follow-up, whichever comes first. Kaplan-Meier estimator was used to estimate survival probability. Median follow-up time was estimated on overall survival by reverse Kaplan-Meier method. Survival difference between groups was evaluated by log-rank test for statistical significance.

Results:A total of 605 patients with newly diagnosed MCL were included in the analysis. The median follow-up time of the whole group was 38 months. The median age was 58 years (range 28-83) with 59% patients under age 60; the M:F ratio was 3.5:1; 76% presented with ECOG PS of 0-1. Eighty-three percent patients had stage 3-4 disease, 38% had intermediate and high risk MIPI scores, and 30% had IPI scores of 3-5. Ki-67 was <30% in 39% patients. Overall, 75% patients received rituximab-containing combination chemotherapy regimens, with the rest receiving chemotherapy without rituximab. The most common chemotherapy in partnership with rituximab was CHOP-based regimens (51%), followed by HyperCVAD (17%), bendamustine (12%), and DHAP (9%). High dose cytarabine was utilized in 30% patients, delivered primarily with the HyperCVAD, DHAP and Nordic MCL regimens. Forty patients (7%) received novel agent-containing induction regimens, including VRCAP with bortezomib and BR plus ibrutinib. Seventy-one patients (12%) moved onto to consolidative autologous stem cell transplant (ASCT) after induction chemotherapy at selected centers. The 3-year OS and 5-year OS were 75.5% and 63.5%, respectively. Clinical parameters such as age <60, ECOG PS 0-1, normal LDH, and absence of BM involvement were significantly associated with improved OS in log-rank test analysis (p<0.001, p<0.001, p<0.001, p<0.001, respectively). Ki67 <30% was associated with improved survival compared to Ki67>30 (p=0.003). OS correlated with MIPI and IPI scores. The 3-year OS rates were 39.7%, 67.7% and 86.7% respectively for high-, intermediate- and low-risk MIPI scores (p<0.001), while 3-yr OS were 25.6%, 51.2%, 78.7% and 93.0% respectively for high-, high-intermediate-, low-intermediate, and low-risk IPI scores (p<0.001). The 5-year OS rates were 32.1%, 58.8% and 67.2% respectively for high-, intermediate- and low-risk MIPI scores (p<0.001), while 5-yr OS were 19.2%, 36.3%, 58.7% and 81.7% respectively for high-, high-intermediate-, low-intermediate, and low-risk IPI scores (p<0.001). Inclusion of rituximab with chemotherapy and consolidative ASCT were significantly associated with improved OS (p=0.016, p<0.001, respectively), while inclusion of high dose cytarabine was associated with improved OS with borderline significance (p=0.065).

Conclusions:This large retrospective dataset of MCL patients who received contemporaneous real-world management in Chinese Hematology Centers confirmed the survival advantage afforded by rituximab-containing chemo-immunotherapy and consolidative autologous stem-cell transplant in first-line setting. The majority of patients seeking care at major medical centers were younger than 60 years of age with good performance status and lower risk MIPI/IPI scores, which correlated with more favorable survival. Incorporation of novel agents signaled infrastructural readiness to explore novel agents and combination in both first-line and relapsed settings.