Real-World Outcomes of Mantle Cell Lymphoma Treated With Rituximab-Based Chemotherapy Regimens: Experience From a Single Institution in Vietnam

Abstract

Introduction

This single-center retrospective study aimed to assess the efficacy and safety of first-line rituximab-containing regimens in treatment-naïve patients with mantle cell lymphoma (MCL) in a resource-constrained setting.

Methods

We included 73 patients diagnosed with MCL between May 2019 and June 2024 who received rituximab-based chemotherapy (RB, RBAC, RDHAP, or RCHOP) at the Vietnam National Cancer Hospital. Clinical characteristics, treatment responses, survival outcomes, and prognostic factors were analyzed.

Results

The median age was 60 years, and the male-to-female ratio was 2.17. Stage IV disease was present in 47.9% of patients and stage III in 38.4%. B symptoms were observed in 27.4%, and Ki-67 >30% in 45.2% of patients. The overall response rate (ORR) was 94.5%, including a complete response rate of 64.4%. The most common grade 3/4 adverse event was neutropenia (17.8%). The 3-year progression-free survival (PFS) and overall survival (OS) rates were 72.6% and 93.2%, respectively. Mantle Cell Lymphoma International Prognostic Index (MIPI) risk classification, treatment response, and extranodal involvement were associated with PFS, whereas OS was primarily influenced by treatment response.

Conclusion

Rituximab-based chemotherapy appears to provide favorable efficacy and manageable toxicity in Vietnamese patients with MCL. These findings suggest that such regimens may remain a feasible first-line option in settings with limited access to novel agents and advanced supportive care.

Keywords

MCL (mantle cell lymphoma)RB/RBAC RDHAP/RCHOP

Introduction

Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin lymphoma with a variable clinical course. MCL can involve lymph nodes and extranodal sites such as the gastrointestinal tract, blood, and bone marrow.^1-3 Mantle cell lymphoma accounts for 3% to 7% of non-Hodgkin lymphomas in the United States and Europe, with an estimated incidence of 4 to 8 cases per million persons per year. The incidence increases with age and appears to be rising in the United States.^4-6 The median age at diagnosis is 68 years. Approximately 75% of patients with MCL are male.⁷

For patients requiring systemic therapy, rituximab combined with chemotherapy is recommended over chemotherapy alone, based on improved survival outcomes without substantial additional toxicity.^8,9 The role of high-dose cytarabine (HiDAC) was established in the MCL-Younger trial, in which 497 patients aged ≤65 years eligible for autologous hematopoietic cell transplantation (HCT) were randomized to receive six cycles of R-CHOP or alternating R-CHOP and R-DHAP (which includes HiDAC).^10-12 Additionally, rituximab plus bendamustine (R-B) demonstrated superior progression-free survival (PFS) with lower toxicity compared with R-CHOP or R-CVP in the randomized StiL and BRIGHT trials involving patients with MCL and indolent lymphomas.^13,14

In Vietnam, treatment selection for MCL is influenced not only by clinical factors such as age, performance status, and disease stage, but also by economic constraints and limited access to novel agents and transplantation. Autologous stem cell transplantation (ASCT) consolidation is not universally available, and financial barriers may prevent eligible patients from undergoing this procedure, even after achieving complete remission. Access to maintenance therapy, PET/CT imaging, molecular diagnostics, and standardized supportive care also varies across institutions. These structural limitations distinguish the local treatment landscape from that of pivotal clinical trials and may affect therapeutic decision-making and long-term outcomes. Furthermore, real-world data on MCL in Vietnam remain scarce, and no prior studies have systematically evaluated first-line rituximab-based regimens in this population. The aim of our study was to assess the efficacy and safety of first-line rituximab-containing regimens in treatment-naïve MCL patients under conditions of economic and essential-medicine limitations.

Patients and Methods

This was a single-center retrospective study conducted at the Vietnam National Cancer Hospital, Hanoi. Consecutive patients diagnosed with mantle cell lymphoma (MCL) between May 2019 and June 2024 and treated with RB/RBAC or R-DHAP/R-CHOP were included. Response assessments were performed by treating investigators. The study was conducted in accordance with the STROBE reporting guidelines.¹⁵

Patients

Eligible adult patients (≥18 years of age) had a histopathologically confirmed diagnosis of mantle cell lymphoma (MCL), supported by immunohistochemical evidence of Cyclin D1 and/or SOX11 expression, with FISH for t(11;14) performed when available. Additional inclusion criteria were measurable disease; an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2; and normal hematologic, renal, and hepatic function (creatinine clearance ≥50 mL/min calculated by the Cockcroft–Gault method; AST, ALT, and total bilirubin ≤2.5 times the upper limit of normal). Patients assigned to the R-CHOP/R-DHAP group were additionally required to have a left ventricular ejection fraction ≥50% and be ≤65 years of age.

Patients were excluded if they had received prior treatment for MCL. Additional exclusion criteria included transformed disease; another malignancy within the previous 3 years, except for definitively treated localized prostate cancer, cervical carcinoma in situ, breast carcinoma in situ, or nonmelanoma skin cancer; significant cardiac disease; evidence of human immunodeficiency virus (HIV) infection; or active hepatitis B or C infection. Pregnant or lactating women were also excluded.

All patient data were anonymized and de-identified prior to analysis to ensure that no individual could be identified.

Treatment

The selection of RB/RBAC or R-DHAP/R-CHOP regimens was determined through multidisciplinary discussion in routine clinical practice. Treatment decisions were based on patients’ age, performance status, comorbidities, disease characteristics, anticipated treatment tolerance, and overall clinical condition. Economic considerations, including the patient’s ability to afford bendamustine-based therapy and, when appropriate, autologous stem cell transplantation (ASCT), were also taken into account.

Given the retrospective and non-randomized design of the study, no predefined allocation protocol was implemented.

Six cycles were planned for all treatment arms (Supplementary Material). In the RB/RBAC arm, rituximab 375mg/m² on day 1, bendamustine 90mg/m²/day on days 1 and 2, plus cytarabine 500mg/m² on days 2,3,4. Cycles of RB/RBAC were repeated every 28 days. In the RDHAP/RCHOP arm, cycles 1 to 3, rituximab 375mg/m² on day 1, dexamethasone 40mg/day on days 1 to 4; cisplatin 100mg/m² day 1; cytarabine 2000mg/m² twice a day on day 2. In cycles 4 to 6, rituximab 375mg/m² on day 1, cyclophosphamide 750mg/m² on day 1, vincristine 1.4mg/m2 (2-mg maximum) on day 1, doxorubicin 50mg/m² on day 1 and prednisolone orally at 100mg/d on days 1 to 5.

Rituximab maintenance was introduced in 2022 following the COVID-19 pandemic. Supportive care measures, including antiemetics, antipyretics, antimicrobial prophylaxis (antibacterial, anti-HSV, and antifungal agents), and granulocyte colony-stimulating factor (G-CSF), were administered according to institutional practice, generally aligned with ESMO and NCCN recommendations.

However, implementation of supportive measures was not fully standardized across treatment groups throughout the study period and was influenced by regimen-specific toxicity profiles and evolving clinical practice patterns.

Data Collection and Endpoints

Clinical data were prospectively accrued from medical records, imaging modalities, pathology reports, and structured patient interviews. Baseline demographic, clinical, laboratory, and histopathological parameters were systematically documented at diagnosis, while treatment-related variables and longitudinal follow-up data were updated at predefined visits or via telephone contact. We maintained continuous communication with patients and healthcare facilities to preclude any loss to follow-up.

The primary endpoint of this study was to assess the overall response rate (ORR) of first-line rituximab-containing regimens in treatment-naïve MCL patients under conditions of economic and essential-medicine limitations. Secondary endpoints were to evaluate progression-free survival (PFS) defined as time from diagnosis to disease progression, relapse, or death, overall survival (OS) defined as the time from diagnosis to death from any cause or last follow-up, associated prognostic factors, safety, and tolerability.

Baseline imaging (PET/CT or whole-body CT) was performed within 4 weeks prior to treatment initiation.

Treatment response was assessed at interim (after 3 cycles) using whole-body computed tomography (CT) and at the end of therapy (after 6 cycles) with positron emission tomography/computed tomography (PET/CT), in accordance with the Lugano 2014 classification criteria. For PET-based evaluations, metabolic response was interpreted using the Deauville five-point scale. In patients who did not undergo PET/CT, response was determined based on CT criteria. In cases where discordant findings were suspected, a multidisciplinary case conference involving radiologists and oncologists was convened to reconcile diagnostic discrepancies and determine the most appropriate management strategy. The efficacy-evaluable population included all treated patients who had baseline imaging and at least one post-baseline response assessment (CT/MRI or PET/CT), or who discontinued treatment due to documented progressive disease, provided no major protocol violations were identified.

The safety population included all patients who received at least one dose of study treatment. Adverse events (AEs) were coded using the Medical Dictionary for Regulatory Activities (MedDRA), version 15.0, and graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

Statistical Analysis

Statistical analyses were performed using SPSS version 23.0 (IBM Corp., Armonk, NY, USA) and R software. Continuous variables were compared using the Mann–Whitney U test, categorical variables using Fisher’s exact test, and survival curves were estimated using the Kaplan–Meier method with comparisons by log-rank test. A two-sided p value <0.05 was considered statistically significant.

Results

Patient Characteristics at Baseline

During the data collection period, all eligible MCL patients treated with rituximab-based chemotherapy were consecutively enrolled, resulting in a total sample of 73 patients. Among 43 patients receiving RB/RBAC, 32 patients were treated with RB and 11 patients were treated with RBAC. On the other hand, 30 patients were treated with RDHAP/RCHOP. Baseline characteristics differed between the two groups with respect to age and sex, reflecting that initial treatment allocation was largely determined by patients’ performance status, comorbidity burden, personal preferences, and financial considerations (Table 1). Notably, patients in the RB/RBAC arm were older, whereas the RDHAP/RCHOP cohort had a higher proportion of male and high-risk patients according to the Mantle Cell Lymphoma International Prognostic Index (MIPI). The RB/RBAC group (n=43) had a median age of 63 years (range, 48–85), compared with 54 years (range, 39–64) in the RDHAP/RCHOP group (n=30). Male patients were more prevalent in the RDHAP/RCHOP arm (86.6% vs 55.8%).

Table 1.

Patient Characteristics at Baseline

Characteristic	All (n=73)	RB/RBAC (n=43)	RDHAP/RCHOP (n=30)	p
Age, median, years (range)	60 (39-85)	63.0 (48-85)	54.0 (39-64)	<0.001^*
Sex (male/female, %)	68.5/31.5	55.8/44.2	86.6/13.3	<0.01 ^@
ECOG				0.728^@
0	64 (87.7)	37 (86.0)	27 (90.0)
1	9 (12.3)	6 (14.0)	3 (10.0)
2	0	0	0
Ann Arbor stage, n (%)				0.464^@
Stage I	1 (1.4)	0	1 (3.3)
Stage II	9 (12.3)	4 (9.3)	5 (16.7)
Stage III	28 (38.4)	18 (41.9)	10 (33.3)
Stage IV	35 (47.9)	21 (48.8)	14 (46.7)
MIPI risk group, n (%)				0.906 ^@
Low	23 (31.5)	14 (32.6)	9 (30.0)
Intermediate	23 (31.5)	14 (32.6)	9 (30.0)
High	27 (37.0)	15 (34.9)	12 (40.0)
B symptoms, n (%)				0.907 ^@
Present	20 (27.4)	12 (27.9)	8 (26.7)
Absent	53 (72.6)	31 (72.1)	22 (73.3)
LDH > ULN, n (%)	18 (24.7)	8 (18.6)	10 (33.3)	0.151 ^@
Ki67 > 30%, n (%)	33 (45.2)	17 (39.5)	16 (53.3)	0.244 ^@

Abbreviation: ECOG, Eastern Cooperative Oncology Group; MIPI, Mantle Cell Lymphoma International Prognostic Index.

^*Mann-Whitney U Test.

^@Fisher’s Exact Test.

ECOG performance status and disease stage distribution were comparable between groups. Most patients had ECOG 0 (86.0% vs 90.0%) and presented with advanced-stage disease (stage III–IV: 90.7% vs 80.0%). The distribution of MIPI risk categories was broadly similar, although the RDHAP/RCHOP cohort included a slightly higher proportion of high-risk patients (40.0% vs 34.9%). The prevalence of B symptoms was also comparable (27.9% vs 26.7%).

Serum lactate dehydrogenase (LDH) levels were elevated in a proportion of patients at diagnosis. The Ki-67 proliferation index was categorized as ≤30% and >30%, with a substantial subset demonstrating a high proliferative index (>30%). Data on pleomorphic and blastoid morphological variants were not systematically documented during the study period and therefore were not included in the comparative analysis.

Efficacy

In this study, the overall response rate (ORR) reached 94.5%, with complete remission (CR) achieved in 64.4% of patients. The analysis demonstrated that RB/RBAC was equivalent to RDHAP/RCHOP with respect to investigator-assessed overall response rate (ORR). Both regimens achieved high response rates, with ORR of 97.7% in the RB/RBAC cohort and 90.0% in the RDHAP/RCHOP cohort (p=0.348). Complete response (CR) was attained in 65.1% of patients treated with RB/RBAC and 63.3% with RDHAP/RCHOP, while partial response (PR) occurred in 32.6% and 26.7%, respectively. Progressive disease (PD) was less frequent in the RB/RBAC group (2.3%) than in the RDHAP/RCHOP group (10.0%), and no patients exhibited stable disease in either arm. Although none of these differences reached statistical significance, RB/RBAC achieved numerically higher ORR and lower rates of disease progression, indicating comparable disease control between the two regimens (Table 2).

Table 2.

Assessment of Response

Response category, n(%)	All (n=73)	RB/RBAC (n=43)	RDHAP/RCHOP (n=30)	p-value	Odds ratio (95% CI)
CR	47 (64.4)	28 (65.1)	19 (63.3)
PR	22 (30.1)	14 (32.6)	8 (26.7)
SD	0	0	0
PD	4 (5.5)	1 (2.3)	3 (10.0)
ORR	69 (94.5)	42 (97.7)	27 (90.0)	0.348 ^@	0.21 (0.021-2.16)

Abbreviation: CR, Complete response; PR, Partial response; SD, Stable disease; PD, Progressive disease; ORR, Overall response rate.

^@Fisher’s Exact Test.

Safety Profile

The safety analysis included 43 patients in the RB/RBAC group and 30 in the RDHAP/RCHOP group (Table 3). A comprehensive summary of treatment exposure and safety outcomes is presented in Table 4. Examination of treatment exposure indicated that 97.7% of patients in the RB/RBAC group and 96.7% in the RDHAP/RCHOP group completed six treatment cycles. Treatment delays occurred in 7.2% of administered cycles, while dose reductions were required in 7.9% of chemotherapy cycles. Treatment discontinuation due to disease progression was observed in 2.7% of patients. All remaining patients completed the planned six cycles.

Table 3.

Nonhematologic AEs and Hematologic Laboratory Data by Chemotherapy Regimen and Prophylaxis GCSF

Toxicity	All (n=73)	RB/RBAC (n=43)	RDHAP/RCHOP (n=30)	p^@
All AEs	37 (50.7)	20 (46.5)	17 (56.7)	0.393
Nonhematologic AE (grade ≥3) occurring in ≥2% of patients
Nausea or Vomiting	5 (6.8)	2 (4.7)	3 (10.0)	0.332
Infusion-related reaction	1 (1.4)	1 (2.3)	0	0.589
Infection	6 (8.2)	4 (9.3)	2 (6.7)	0.521
Pneumonia/respiratory infection	6 (8.2)	6 (14.0)	0	0.036
Renal failure (grade 1)	6 (8.2)	0	6 (20.0)	0.003
Hematologic laboratory data
Absolute neutrophil count (grade ¾)	13 (17.8)	6 (14.0)	7 (23.3)	0.303
Hemoglobin (Grade 1 to 3)	17 (23.3)	8 (18.6)	9 (30.0)	0.257
Platelet count (grade ¾)	4 (5.5)	1 (2.3)	3 (10.0)	0.299
Hospitalisations due to serious AEs	9 (12.3)	5 (11.6)	4 (13.3)	1.00
Treatment-related mortality	0	0	0

Abbreviation: AE, Adverse event.

^@Fisher’s Exact Test.

Table 4.

Primary Prophylaxis, ASCT Consolidation and Rituximab Maintenance

Prophylaxis	RB/RBAC (n=43)	RDHAP/RCHOP (n=30)
Primary prophylaxis GCSF	26 (60.5)	30 (100)
Prophylaxis acyclovir	26 (60.5)	30 (100)
Prophylaxis cotrimoxazole	26 (60.5)	30 (100)
Prophylaxis fluconazole	0	30 (100)
ASCT consolidation	0	1 (3.0)
Rituximab maintenance	16 (37.2)	10 (33.3)

Abbreviation: ASCT, GCSF, Granulocyte colony-stimulating factor; Autologous Stem Cell Transplantation.

The overall incidence of treatment-related adverse events was 50.7%, of which 12.3% required hospitalization due to severe toxicity. Notably, no treatment-related mortality was observed. The safety profiles of RB/RBAC and RDHAP/RCHOP were largely comparable, though certain adverse events demonstrated regimen-specific patterns. The overall incidence of grade ≥3 nonhematologic toxicities did not differ significantly between cohorts. Notably, pneumonia or respiratory infections occurred more frequently in the RB/RBAC group, while renal toxicity was observed exclusively in patients treated with RDHAP/RCHOP. Hematologic adverse events were frequent in both arms, with a tendency toward higher rates of neutropenia, leukopenia, anemia, and thrombocytopenia in the RDHAP/RCHOP cohort; however, these differences were not statistically significant. Taken together, these results indicate that both regimens are tolerable with prophylactic G-CSF, yet their distinct toxicity profiles may be clinically relevant in guiding therapeutic decision-making.

Supportive Care, ASCT Consolidation and Rituximab Maintenance

Supportive care measures included prophylactic treatments such as Granulocyte Colony-Stimulating Factor (G-CSF), Cotrimoxazole, Fluconazole, and Acyclovir, administered to all patients undergoing the RDHAP/RCHOP regimen. Furthermore, from 2022 onwards, G-CSF, Acyclovir, and Cotrimoxazole were also provided to patients receiving RB/RBAC according to ESMO guideline.¹⁶ Following the year 2022, Rituximab maintenance therapy was instituted for patients. Supportive care approaches varied markedly between the treatment arms. In the RDHAP/RCHOP cohort, prophylaxis with G-CSF, acyclovir, cotrimoxazole, and fluconazole was uniformly administered, whereas in the RB/RBAC group these measures were applied less consistently, with antifungal prophylaxis omitted entirely. The use of ASCT consolidation was minimal, likely reflecting the advanced age and baseline characteristics of the study population. Rituximab maintenance was employed in approximately one-third of patients in both cohorts, with no appreciable difference between regimens (Table 5). Overall, these observations indicate that supportive care strategies differed according to treatment regimen, while both consolidation and maintenance were only sparingly implemented.

Table 5.

Cycle Delays, Dose Reductions, Early Discontinuations, and Reasons for Discontinuation

Treatment exposure reporting	All (432 cycles)	RB/RBAC (255 cycles)	RDHAP/RCHOP (177 cycles)
Cycle delays	31 (7.2%)	18 (7.0%)	13 (7.3%)
Dose reductions (cycles)^#	34 (7.9%)	22(8.6%) (reduced 50% dose of bendamustin)	12 (6.8%) (reduced 50% dose of cytarabine and cisplatin)
Early discontinuations (n=73)	2 (2.7%)	1 (1.3%)	1 (1.3%)
Reasons for discontinuation (n=73)	2 (2.7%)	Disease progression	Disease progression

^#Dosage reduction is recommended according to NCCN guidelines.

Survival Analysis

During a median follow-up of 25 months (3-61 months), 20 (27.4%) patients progressed, and 12 (16.4%) patients died. At the data cutoff date (June 30, 2024), the 3-year PFS was 72.6% and the 3-year OS was 93.2% (Figure 1). Table 6 showed PFS univariate analyses according to prognostic factors. At 3 years, PFS did not differ significantly between patients treated with RB/RBAC and those receiving RDHAP/RCHOP (74.4% vs 70.0%, p=0.585) (Figure 2, left panel). Proliferative activity, as measured by Ki-67, showed a trend toward inferior PFS in patients with Ki-67 >30% compared with ≤30% (63.6% vs 80.0%, p=0.222). MIPI classification demonstrated clear prognostic relevance, with 3-year PFS rates of 91.3%, 82.6%, and 48.1% in the low-, intermediate-, and high-risk groups, respectively (p=0.018). Treatment response was the strongest predictor of PFS: patients achieving CR had a markedly higher 3-year PFS compared with PR or PD (80.9% vs 68.2% vs 0%, p<0.001) (Figure 3, left panel). Extranodal involvement was significantly associated with worse PFS (62.9% vs 81.6% in patients without extranodal disease, p=0.014). Although not statistically significant, rituximab maintenance was associated with a numerical improvement in PFS (92.3% vs 61.7%, p=0.262). Table 7 showed OS univariate analyses according to prognostic factors. For OS, outcomes were comparable between RB/RBAC and RDHAP/RCHOP (83.7% vs 83.3%, p=0.811) (Figure 2, right panel). Patients with Ki-67 ≤30% had better OS than those with higher Ki-67 (90.0% vs 75.8%, p=0.168). MIPI showed a trend toward prognostic stratification, with 3-year OS rates of 95.7%, 87.0%, and 70.4% in the low-, intermediate-, and high-risk groups; however, this difference did not reach statistical significance (p=0.136). Response status strongly predicted OS, with 3-year survival of 91.5% in CR, 72.7% in PR, and 50.0% in PD (p<0.001) (Figure 3, right panel). Extranodal involvement was associated with numerically inferior OS compared with nodal-only disease (80.0% vs 86.8%, p=0.119). Rituximab maintenance yielded higher 3-year OS (96.2% vs 76.6%), though not statistically significant (p=0.511). This analysis demonstrated no significant survival differences between RB/RBAC and RDHAP/RCHOP. Instead, survival was largely dictated by well-established prognostic determinants, including MIPI risk group, extranodal involvement, and depth of response. Achievement of complete remission was the most powerful predictor of both PFS and OS, underscoring the critical importance of attaining deep initial responses. Although statistical significance was not achieved, rituximab maintenance showed numerically higher PFS and OS rates, warranting further evaluation in studies with longer follow-up.

Figure 1.

PFS and OS Kaplan-Meier curve. NR, not reached

Table 6.

Relationship Between Progression-free Survival and Some Prognostic Factors by Log-Rank Test

Charcteristics	N	3-year PFS	HR (95%CI)	p
Regimens
RB/RBAC	43	74.4%	0.78 (0.32-1.90)	0.585
RDHAP/RCHOP	30	70.0%		0.585
Ki67
≤30%	40	80.0%	1.73 (0.70-4.25)	0.222
>30%	33	63.6%		0.222
MIPI risk classification
Low risk	23	91.3%	0.41 (0.21-0.81)	0.018
Intermediate risk	23	82.6%
High risk	27	48.1%
Response classification^a
CR	47	80.9%	0.18 (0.09-0.36)	<0.001
PR	22	68.2%
PD	4	0%
Staging^b
I-II	10	80.0%	1.65 (0.38-7.21)	0.498
III, IV	63	71.4%		0.498
Extranodal lesion
No	38	81.6%	0.33 (0.13-0.84)	0.014
Yes	35	62.9%		0.014
Rituximab maintenance
No maintenance	47	61.7%	0.43 (0.09-1.96)	0.262
Maintenance	26	92.3%		0.262

Abbreviation: MIPI, Mantle Cell Lymphoma International Prognostic Index.

^aAccording to Lugano staging classification, HR, hazard ratios.

^bAccording to Ann Arbor Staging of lymphoma.

Figure 2.

Log-rank analysis of the relationship between PFS, OS and regimen subgroup. mPFS, median PFS; mOS, median OS; NR, not reached

Figure 3.

Log-rank analysis of the relationship between PFS, OS and response subgroup. mPFS, median PFS; mOS, median OS; NR, not reached

Table 7.

Relationship Between Overall Survival and Some Prognostic Factors by Log-Rank Test

Characteristics	N	3-year OS	HR (95%CI)	p
Regimens
RB/RBAC	43	83.7%	0.86 (0.27-2.77)	0.811
RDHAP/RCHOP	30	83.3%		0.811
Ki67
≤30%	40	90.0%	2.27 (0.68-7.60)	0.168
>30%	33	75.8%		0.168
MIPI risk classification
Low risk	23	95.7%		0.136
Intermediate risk	23	87.0%	0.43 (0.18-1.04)
High risk	27	70.4%
Response classification^a
CR	47	91.5%	0.253 (0.126-0.510)	<0.001
PR	22	72.7%
PD	4	50.0%
Staging^b
I-II	10	90.0%	2.12 (0.27-16.68)	0.463
III, IV	63	82.5%		0.463
Extranodal lesion
No	38	86.8%	0.40 (0.12-1.30)	0.119
Yes	35	80.0%		0.119
Rituximab maintenance
No maintenance	47	76.6%	0.49 (0.05-4.25)	0.511
Maintenance	26	96.2%		0.511

Abbreviation: MIPI, Mantle Cell Lymphoma International Prognostic Index.

^aAccording to Lugano staging classification, HR, hazard ratios.

^bAccording to Ann Arbor Staging of lymphoma.

Discussion

This real-world study demonstrates that RB/RBAC achieved response rates and short-term survival outcomes comparable to RDHAP/RCHOP in treatment-naïve mantle cell lymphoma (MCL). Rather than indicating superiority of one regimen over another, our findings suggest that both approaches remain clinically active options in routine practice.

Our results are consistent with prior randomized trials showing that bendamustine-based regimens provide durable disease control with a favorable toxicity profile compared with R-CHOP–based approaches. In the randomized StiL¹³ and BRIGHT¹⁴ trials, R-B demonstrated superior progression-free survival with lower toxicity compared with R-CHOP or R-CVP in patients with MCL and indolent lymphomas. More recently, Visco et al reported encouraging long-term outcomes with R-BAC500 in elderly patients, with sustained remissions and no late relapses beyond six years in responders.¹⁷ The role of high-dose cytarabine (HiDAC) has been firmly established in the MCL-Younger trial, in which alternating R-CHOP/R-DHAP improved overall survival and time to treatment failure compared with R-CHOP alone after long-term follow-up.^11,18 These findings support the continued use of cytarabine-containing regimens in fit, transplant-eligible patients.

Long-term follow-up of cytarabine-containing regimens has shown durable remissions in more than 40% of patients at 10 years, with a plateau in treatment failure after 8 years. These data support high-dose cytarabine–based therapy as a standard option for younger, transplant-eligible patients.

Retrospective data indicate that bendamustine plus rituximab (BR), particularly when followed by ASCT and rituximab maintenance, can achieve outcomes comparable to R-CHOP/R-DHAP–based strategies. While the relative contribution of maintenance therapy remains unclear, real-world analyses suggest that BR combined with rituximab maintenance may provide similar effectiveness even without ASCT, supporting its use in settings where transplantation access is limited.^19-21

At the current follow-up, no significant differences in PFS or OS have been observed between patients who received maintenance therapy and those who did not. However, given the relatively short observation period, longer follow-up is required to adequately evaluate the potential survival impact of rituximab maintenance.

As our institution lacks an on-site transplant unit and access to ASCT is limited by financial and logistical constraints, only one patient underwent transplantation at an external center. This patient achieved complete response after RDHAP/RCHOP and remained in remission at last follow-up. Importantly, the clinical context in Vietnam should be considered when interpreting the favorable ORR and survival outcomes observed in this study. Maintenance rituximab was only incorporated into routine clinical practice in 2022, following expanded health insurance coverage. In our cohort, 35.6% of patients received rituximab maintenance therapy after this policy change, reflecting improving access to this strategy. In contrast, access to ASCT remains limited at our center and across Vietnam, representing a significant therapeutic constraint. Despite these limitations, the observed outcomes are encouraging and may reflect careful patient selection and optimization of available therapies. We have also strengthened collaborations with transplant centers to improve access to ASCT.

Furthermore, access to novel therapies—including BTK inhibitors, CAR-T cell therapy, and bispecific antibodies—remains markedly restricted in Vietnam, which may partly explain differences in outcomes compared with those reported in developed settings. Ongoing efforts to expand access to these treatments, including pursuing governmental approval, are expected to improve patient outcomes in the future.

In univariate analyses, MIPI classification, disease stage, and treatment response were significantly associated with PFS, while treatment response also predicted OS. These findings are consistent with established prognostic models in MCL and reinforce the clinical relevance of conventional risk stratification in routine practice. The survival benefit associated with rituximab-containing regimens has been well documented. A meta-analysis of seven studies including 1,943 patients with MCL or indolent lymphomas demonstrated improved OS, higher response rates, and better disease control with rituximab-based therapy compared with chemotherapy alone. In the MCL subgroup, a significant survival advantage was observed (HR 0.60, 95% CI 0.37–0.98). Consistent with this, observational data have reported prolonged median survival with the addition of rituximab (37 vs 27 months).²²

The analysis of AEs and other safety parameters showed that there were some statistically significant differences between the treatment regimens. The higher rate of pneumonia observed in the RB/RBAC cohort should be interpreted with caution. Variations in supportive care strategies over the study period, particularly regarding antimicrobial prophylaxis, may have influenced infection risk. Given the retrospective design and limited sample size, residual confounding cannot be excluded. Grade 1 renal impairment was observed exclusively in six patients in the RDHAP/RCHOP group following RDHAP administration, likely reflecting cisplatin-related nephrotoxicity. Despite supportive measures including hydration and diuretics, five of these patients had persistent low-grade renal dysfunction at last follow-up.

In the MCL Younger trial, grade 3–4 hematologic toxicities were frequent in the R-CHOP/R-DHAP arm, including anemia (29%), neutropenia (75%), and thrombocytopenia (73%), while renal toxicity of grade 1–2 occurred in 43% and grade 3–4 in 1% of patients. Infections (grade 3–4) were reported in 9% of cases. Toxicity generally decreased over time in both treatment groups, although low-grade renal impairment remained stable. Overall, hematologic, renal, infectious, and cardiac toxicities were more common in the R-DHAP arm.¹⁸

Compared with these data, the incidence of adverse events in our cohort appeared lower. This difference may partly reflect systematic prophylactic strategies and supportive care measures implemented in our practice, although differences in study design and patient selection should be considered when interpreting cross-trial comparisons.

Importantly, differences in supportive care implementation between regimens may have influenced toxicity and outcome comparisons. In our cohort, antimicrobial prophylaxis and routine G-CSF support were consistently administered in patients receiving R-DHAP/R-CHOP due to anticipated hematologic toxicity, whereas prophylaxis in the RB/RBAC group was less systematic prior to 2022. These real-world variations reflect routine practice but may represent a source of confounding that limits direct comparability between treatment groups.

This study had some limitations. Firstly, the small sample size and retrospective design limited statistical power, particularly for detecting differences between subgroups in survival and toxicity outcomes. Secondly, the selection between RB/RBAC and RDHAP/RCHOP was based on clinical judgment rather than randomization, with economic considerations also influencing treatment choice. This may have introduced selection bias and acted as a potential confounding factor in the interpretation of treatment outcomes. Conversely, supportive care measures—including antimicrobial prophylaxis and G-CSF use—were not fully standardized across patients. This represents a limitation of the study and may have influenced infection rates and hematologic toxicity profiles, particularly when comparing cytarabine-intensive and bendamustine-based regimens. Another important limitation relates to incomplete risk stratification Contemporary prognostic markers in mantle cell lymphoma—such as NGS profiling, TP53 alterations, blastoid/pleomorphic morphology, and high Ki-67—were not uniformly assessed; TP53 testing and detailed morphological subclassification are not consistently available at our institution. The absence of these high-risk biological parameters may compromise prognostic accuracy, limit between-group comparability, and confound analyses based on conventional indices (e.g., MIPI and Ki-67). Efforts are underway to secure governmental support to strengthen diagnostic capacity. Moreover, access to novel therapies in Vietnam—including BTK inhibitors, CAR-T cell therapy, and bispecific antibodies—remains markedly limited, which may contribute to inferior treatment outcomes compared with those reported in developed settings. We are actively pursuing governmental approval for these agents, with the aim of improving patient survival in the future. Further, the median follow-up of 25 months is relatively short, and therefore long-term survival outcomes, late relapses, and delayed toxicities could not be fully assessed. Our findings should thus be considered preliminary. Larger studies with extended follow-up are required to better define long-term survival and validate prognostic factors.

Conclusion

This real-world observational study suggests that rituximab-based chemotherapy was associated with favorable response rates and encouraging short-term survival outcomes in Vietnamese patients with mantle cell lymphoma.

Given the retrospective design and potential confounding factors, these findings should be interpreted with caution and considered hypothesis-generating. Further prospective studies with larger sample sizes and longer follow-up are warranted.

Supplemental Material

Supplemental Material -Real-World Outcomes of Mantle Cell Lymphoma Treated With Rituximab-Based Chemotherapy Regimens: Experience From a Single Institution in Vietnam

Supplemental Material for Real-World Outcomes of Mantle Cell Lymphoma Treated With Rituximab-Based Chemotherapy Regimens: Experience From a Single Institution in Vietnam by Hung Kien Do, Nga Huyen Do, Van Tai Nguyen, Tung Thanh Nguyen, and Binh Duc Vu in Cancer Control.

Footnotes

ORCID iDs

Hung Kien Do

Nga Huyen Do

Van Tai Nguyen

Tung Thanh Nguyen

Ethical Considerations

The study was approved by the Institutional Ethics Review Board of the Vietnam National Cancer Hospital in Hanoi, Vietnam (Approval Number: 3375/BVK and 3470/BVK; approval date: 22/11/2024). Informed consent was waived because of the retrospective design of the study. The patient data were maintained with confidentiality, in compliance with the Declaration of Helsinki of 1975, as revised in 2024.

Author Contributions

Conception and design: Hung Kien Do, Nga Huyen Do, Tung Thanh Nguyen, Van Tai Nguyen.

Collection and assembly of data: All authors.

Data analysis and interpretation: Hung Kien Do, Nga Huyen Do, Tung Thanh Nguyen and Van Tai Nguyen.

Writing the main manuscript text: All authors.

Final approval of manuscript: All authors.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

The data generated in the present study may be requested from the corresponding author.*

Supplemental Material

Supplemental material for this article is available online.

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