Treatment evolution and survival impact of consolidation therapies in mantle cell lymphoma: insights from an Asia-Pacific real-world registry

Dear Editor,

Treatment strategies for newly diagnosed mantle cell lymphoma (MCL) vary substantially according to patient age, performance status, and comorbidities [1]. Intensive cytarabine-based regimens followed by upfront autologous stem cell transplantation (ASCT) has been preferred for younger or fit patients, while less intensive ones for older or frail patients. Rituximab maintenance therapy is recommended for both groups across major guidelines [2]. While several large real-world studies have characterized MCL management in Western populations, comparable comprehensive analyses from the Asia-Pacific (APAC) region are limited [3–6]. To address this knowledge gap, we conducted a multinational, multicenter retrospective registry study to delineate real-world treatment patterns, evaluate survival outcomes, and assess the impact of upfront ASCT and rituximab maintenance in newly diagnosed MCL patients across the APAC region.

This study included patients with newly diagnosed MCL between January 2008 and November 2020 who received treatment at 31 academic centers across eight APAC jurisdictions: China, Indonesia, Malaysia, Japan, Singapore, South Korea, Taiwan, and Thailand. This study was approved by the institutional review boards of all participating institutions. Survival data were updated through the cutoff date of December 15, 2023. A propensity score model was employed to generate inverse probability of treatment weighting (IPTW), to adjust for imbalances in baseline characteristics between the treatment groups.

A total of 642 patients were included (Supplementary Fig. 1). The median age at diagnosis was 62 years (range, 26–90 years; Supplementary Table 1), and 482 patients (75.1%) were male. Most patients (87.9%) presented with advanced-stage disease (stage III-IV). The blastoid or pleomorphic variant was identified in 65 patients (10.1%). According to the MCL International Prognostic Index (MIPI), 301 patients (51.7%) were classified as low-risk, 145 (24.9%) as intermediate-risk, and 136 (23.4%) as high-risk.

Among these patients, 557 (86.8%) received rituximab-based regimens as first-line therapy (Supplementary Table 2). The most common regimen was rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens (n = 272, 42.4%), followed by cytarabine-containing regimens (n = 199, 31.0%). Bendamustine-rituximab (BR) was used in 58 patients (9.0%). Treatment patterns differed significantly by age. Among elderly patients (≥65 years, n = 280), R-CHOP or R-CHOP–like regimens predominated (50.4%), whereas younger patients (<65 years, n = 362) were more often treated with cytarabine-containing regimens (45.9%) compared with older patients (11.8%). The use of R-CHOP or R-CHOP-like regimens declined from 51.6% in 2008 to 26.7% in 2020, whereas BR increased from 0% to 40.4% (Supplementary Fig. 2A). Similar trends were observed across age groups (Supplementary Fig. 2B, 2C).

At a median follow-up of 83.3 months (95% confidence interval [CI], 80.2–90.6), the median PFS and OS for the entire cohort were 35.8 months (95% CI, 32.3–41.1) and 87.8 months (95% CI, 74.5–101.0), respectively (Supplementary Fig. 3A, 3B). Patients younger than 65 years who achieved at least a partial response (PR) to first-line therapy were considered eligible for ASCT (n = 294). Baseline characteristics of ASCT-eligible patients are presented in Supplementary Table 3. Among them, 71 patients (24.1%) underwent upfront ASCT. The utilization of upfront ASCT gradually increased from 13.8% in 2013 to 40.0% in 2020 (Supplementary Fig. 4). Upfront ASCT was associated with significantly superior survival outcomes, with a 5-year PFS of 63.8% vs. 45.1% (hazard ratio [HR] 0.611; 95% CI 0.411–0.909; P = 0.015) and a 5-year OS of 88.3% vs. 63.8% (HR 0.421; 95% CI 0.234–0.758; P = 0.003) compared with no upfront ASCT (Fig. 1A, B). After applying IPTW, baseline characteristics were well balanced between groups (Supplementary Table 4), and the survival benefit of ASCT persisted: 5-year PFS of 66.1% vs. 44.9% (HR 0.558; 95% CI 0.369–0.845; P = 0.006) and 5-year OS of 86.1% vs. 73.8% (HR 0.312; 95% CI 0.159–0.611; P = 0.001) (Fig. 1C, D). Subgroup analysis following IPTW demonstrated consistent PFS and OS benefits across most subgroups (Fig. 1E, F). Notably, patients with blastoid/pleomorphic variants, patients with Ki-67 ≥ 30%, PR after induction therapy, or absence of rituximab maintenance exhibited particularly pronounced PFS benefits from ASCT.

Fig. 1. Impact of upfront autologous stem cell transplantation (ASCT) in ASCT-eligible patients.

PFS (A) and OS (B) according to upfront ASCT. IPTW-weighted PFS (C) and OS (D). Forest plots for PFS (E) and OS (F), comparing ASCT vs. no ASCT after applying IPTW. (^*) Log-rank test; (^†) weighted log-rank test.

Patients who achieved at least a PR to first-line therapy and remained progression-free for ≥ 3 months after completion of treatment were considered eligible for rituximab maintenance (n = 471). Baseline characteristics of maintenance-eligible patients are summarized in Supplementary Table 5. Among them, 57 patients (12.1%) received rituximab maintenance therapy. The use of rituximab maintenance increased over time, from 2017 onwards, reaching 28.0% in 2020 (Supplementary Fig. 4). Rituximab maintenance was associated with significantly superior survival outcomes, with a 5-year PFS of 55.1% vs. 39.1% (HR 0.575; 95% CI 0.387–0.856; P = 0.006) and a 5-year OS of 84.2% vs. 64.5% (HR 0.390; 95% CI 0.217–0.699; P = 0.001) compared with no rituximab maintenance (Fig. 2A, B). After applying IPTW, baseline characteristics were well balanced between groups (Supplementary Table 6), and the survival advantage of rituximab maintenance persisted, with 5-year PFS of 57.4% vs. 39.7% (HR, 0.541; 95% CI, 0.316–0.929; P = 0.026) and a trend toward improved OS of 79.5% versus 65.5% (HR, 0.532; 95% CI, 0.246–1.150; P = 0.109) (Fig. 2C, D). Subgroup analysis following IPTW demonstrated consistent PFS and OS benefits across most subsets (Fig. 2E).

Fig. 2. Impact of rituximab maintenance therapy in maintenance-eligible patients.

PFS (A) and OS (B) according to rituximab maintenance. IPTW-weighted PFS (C) and OS (D) according to rituximab maintenance. Forest plots for PFS (E) and OS (F), comparing maintenance vs. no maintenance after applying IPTW. (^*) Log-rank test; (^†) weighted log-rank test.

This multinational, multicenter, retrospective registry study provides contemporary real-world insights into the treatment patterns and outcomes of MCL across the APAC region. Several distinguishing features were observed compared with Western cohorts. The median age at diagnosis was 62 years, younger than the > 68 years typically reported in Western studies, contributing to a more favorable MIPI risk profile (23.4% high-risk vs. >40% in Western series) [3, 7, 8]. Despite these demographic differences, survival outcomes in our cohort were comparable to those reported elsewhere.

Treatment patterns evolved over the study period. Although R-CHOP or R-CHOP-like regimens remained the common first-line therapies overall, their use declined from 51.6% in 2008 to 26.7% in 2020, paralleled by a marked rise in BR, which became the predominant regimen by 2020 (40.4%). This shift was evident across age groups and aligns with a trend reported in a recent U.S. real-world study [3].

Consolidation therapies were underutilized. Only 24.1% of ASCT-eligible patients underwent transplantation, consistent with reports from large U.S. cohorts showing upfront ASCT rates of 10–25% among younger patients [3, 9, 10]. Likewise, rituximab maintenance was administered to only 12.1% of eligible patients—substantially lower than the 25–40% reported in Western real-world cohorts [3, 4, 7]. Limited access and reimbursement restrictions across several APAC countries likely contribute to this disparity. Nevertheless, maintenance use increased from 2017 onwards, reaching 28.0% in 2020.

Upfront ASCT was associated with significantly improved PFS and OS among eligible patients, with consistent benefits observed across most subgroups. IPTW analysis confirmed these findings, reinforcing the robustness of the survival benefit despite inherent limitations of retrospective data. These results align with a prior large real-world study demonstrating superior outcomes with upfront ASCT in younger patients [6]. Our analysis demonstrated a clear PFS benefit in patients achieving PR, but not in those achieving CR, implying that ASCT may particularly benefit patients with suboptimal responses to induction therapy. These findings are consistent with emerging evidence questioning the necessity of ASCT in the era of novel agents, including the TRIANGLE trial which suggests that addition of ibrutinib to induction therapy might allow omission of ASCT without compromising survival in eligible patients, and the ECOG-ACRIN EA4151 study showing no additional ASCT benefit among MRD-negative patients [11, 12]. The interplay between ASCT and maintenance therapy may also influence outcomes. Recent data indicate that ASCT confers a survival advantage primarily in patients who do not receive maintenance [4]. Consistent with this, our subgroup analysis showed a pronounced PFS benefit of ASCT among patients who did not receive maintenance therapy, but not among those who did. ASCT may also retain particular value in biologically high-risk disease. Our subgroup analysis revealed clear PFS benefits in patients with Ki67 ≥ 30% or blastoid/pleomorphic variant, consistent with findings from the TRIANGLE trial and a large real-world study [6, 13].

Rituximab maintenance therapy in our study conferred significant PFS and OS benefits, consistent with the pivotal MCL Elderly and LyMA trials and multiple real-world analyses [3, 4, 14, 15]. The OS benefit did not reach statistical significance in the IPTW-adjusted analysis, likely due to the small number of patients receiving maintenance therapy.

This study had several limitations. The retrospective nature might introduce selection bias. While IPTW analysis was implemented to minimize bias, unmeasured clinical factors such as TP53 mutations could not be accounted for. Additionally, response assessments were conducted locally without central review.

In summary, this large multinational registry provides the most comprehensive real-world overview of MCL management in the APAC region. Utilization of both upfront ASCT and rituximab maintenance remains low, underscoring a persistent gap between guidelines and practice. Nevertheless, both strategies significantly improved survival outcomes. In contexts where BTK inhibitor-containing regimens as the first-line therapy are not universally accessible, our data support the continued role of ASCT, particularly for high-risk patients and those with suboptimal induction responses. ASCT and rituximab maintenance appear to provide complementary benefits, supporting their integration into treatment algorithms.

Author contributions

HC, DHY and WSK designed the study. HC, KK, and DHY wrote the manuscript. HC performed the statistical analysis. KK DHY and WSK validated the findings and contributed to data interpretation. DHY and WSK supervised the study. All authors enrolled patients, gathered clinical information, reviewed the clinical data, and critically revised the manuscript. All authors approved the final version of the manuscript.

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare no competing interests.

Supplementary information

The online version contains supplementary material available at 10.1038/s41408-026-01521-y.