Treatment patterns and survival outcomes in patients with Mantle Cell Lymphoma: Interim report of the Asia-Pacific multinational prospective registry study

Abstract

Abstract Introduction We conducted a multinational, multicenter prospective registry study to better define the treatment patterns and survival outcomes of newly diagnosed patients with mantle cell lymphoma (MCL) in the Asia-Pacific region. Methods Clinical and laboratory data collection from newly diagnosed MCL patients has been ongoing since January 2019 from 27 hospitals in Asian countries, including China, Indonesia, Japan, Malaysia, Singapore, South Korea, Taiwan, and Thailand. An interim analysis was conducted on 132 patients diagnosed with MCL between January 2019 and November 2024. Results The median age was 65 years (range, 35–86), and 116 patients were male (87.9%). The majority of the patients had stage 3 or 4 diseases (n=111, 84.1%). According to the MIPI score, risk was low in 49 (37.1%), intermediate in 46 (34.8%), and high in 34 (25.8%) patients (unknown in 3 [2.3%] patients). Most of the patients (n=122, 92.4%) were treated with systemic chemotherapy, while 4 (3.0%) patients were treated with radiotherapy, and 6 (4.5%) were managed with a watch-and-wait strategy. The most frequently administered 1st line regimen was BR (bendamustine and rituximab) (n=72, 59.0%), followed by R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) (n=19, 15.6%), VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone) (n=18, 14.8%), and cytarabine-containing regimens (n=10, 8.2%; including R-Hyper-CVAD [n=4], R-CHOP/R-DHAP [n=4], NORDIC regimen [n=1], R-DHAP [n=1]). BR was the most frequently used regimen across both younger (age <70, 57.5%) and older patients (age ≥70, 61.5%). The treatment response to 1st line regimens was available in 113 patients. The response rates (ORR/CR rate) for each regimen were as follows; 95.6%/76.5% for BR, 78.9%/42.1% for R-CHOP, 82.3%/64.7% for VR-CAP, and 100.0%/100.0% for cytarabine-containing regimens. With a median follow-up duration of 28.5 months, 2-year progression-free survival (PFS) rate was 67.5%, and 2-year overall survival (OS) rate was 81.7%. R-CHOP was associated with worse PFS compared with the other regimens, with a 2-year PFS rate of 26.9% for R-CHOP, while it was 75.0% for BR, 81.4% for VR-CAP, and 77.7% for cytarabine-containing regimens (P<0.001). The role of upfront ASCT was evaluated in patients who are < 70 years old and achieved at least partial response (PR) to 1st line treatment (n = 72). A significantly higher proportion of patients in the non-ASCT group (n=51) received rituximab maintenance compared with the ASCT group (n=21) (31.4% vs. 4.8%, P=0.035). There were no significant differences in PFS and OS between the ASCT and non-ASCT groups, with a 2-year PFS rate of 78.9% vs. 78.4% (P = 0.770) and a 2-year OS rate of 89.9% vs. 89.5% (P=0.071), respectively. The role of maintenance treatment was evaluated in patients who achieved PR or better to 1st line treatment and did not experience disease progression within 3 months after completion of 1st line treatment (n=90). A significantly higher proportion of patients in the non-maintenance group (n=66) received upfront ASCT compared with those who received rituximab maintenance (n=24) (31.8% vs. 4.2%, P=0.015). There were no significant differences in survival outcomes between rituximab maintenance and no maintenance group, with a 2-year PFS rate of 88.9% vs. 78.9% (P=0.320) and 2-year OS rate of 95.2% vs. 93.1% (P = 0.360). A total of 33 patients were treated with 2nd line regimens. The most frequently administered 2nd line regimen was ibrutinib (n=23, 69.7%), followed by zanubrutinib (n=8, 24.2%), pirtobrutinib (n=1, 3.0%) and CHOP (n=1, 3.0%). The treatment response to 2nd line regimens was available in 24 patients, and the ORR and the CR rate among these patients were 74.9% and 29.1%, respectively. The median 2nd PFS was 9.2 months. Conclusion In the contemporary era, majority of MCL patients in the Asia-Pacific region received rituximab-based regimens as first-line treatment, with the BR regimen being the most commonly used across both young and elderly patients. R-CHOP was associated with inferior survival outcomes compared to other regimens. The rate of upfront ASCT and usage of rituximab maintenance was relatively low. No significant differences in survival outcomes have been observed yet according to upfront ASCT or rituximab maintenance. The majority of patients received BTKi as 2nd line treatment, with ibrutinib being the most frequently used BTKi.