Survival in mantle cell lymphoma after frontline treatment with R-bendamustine, R-CHOP and the Nordic MCL2 regimen – a real world study on patients diagnosed in Sweden 2007-2017

Albertsson-Lindblad, Alexandra; Pálsdóttir, Þorgerður; Smedby, Karin E.; Weibull, Caroline E.; Glimelius, Ingrid

doi:10.3324/haematol.2021.279037

Cited by 12 publications

(11 citation statements)

References 14 publications

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“…Results from chemoimmunotherapy were also evaluated in real‐world 126 retrospective analyses, and they further establish the data from clinical trials and demonstrate an improvement in patient survival by era 127 …”

Section: Introductionmentioning

confidence: 74%

“…Maintenance rituximab after BR did not demonstrate an improvement in outcomes. 125 Results from chemoimmunotherapy were also evaluated in realworld 126 retrospective analyses, and they further establish the data from clinical trials and demonstrate an improvement in patient survival by era. 127 Nonchemotherapy options-Lenalidomide with rituximab was investigated in 38 patients.…”

Section: Prognostic Factorsmentioning

confidence: 83%

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Mantle cell lymphoma in 2022—A comprehensive update on molecular pathogenesis, risk stratification, clinical approach, and current and novel treatments

Jain

Wang

2022

American J Hematol

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The field of mantle cell lymphoma (MCL) has witnessed remarkable progress due to relentless advances in molecular pathogenesis, prognostication, and newer treatments. MCL consists of a spectrum of clinical subtypes. Rarely, atypical cyclin D1-negative MCL and in situ MCL neoplasia are identified. Prognostication of MCL is further refined by identifying somatic mutations (such as TP53, NSD2, KMT2D), methylation status, chromatin organization pattern, SOX-11 expression, minimal residual disease (MRD), and genomic clusters. Lymphoid tissue microenvironment studies demonstrated the role of B-cell receptor signaling, nuclear factor kappa B (NF-kB), colony-stimulating factor (CSF)-1, the CD70-SOX-11 axis. Molecular mechanism of resistance, mutation dynamics, and pathogenic pathways (B-cell receptor (BCR), oxidative phosphorylation, and MYC) were identified in mediating resistance to various treatments (bruton tyrosine kinase (BTK) inhibitors [ibrutinib, acalabrutinib]. Treatment options range from conventional chemoimmunotherapy and stem cell transplantation (SCT) to targeted therapies against BTK (covalent and noncovalent), Bcl2, ROR1, cellular therapy such as anti-CD19 chimeric antigen receptor therapy (CAR-T), and most recently bispecific antibodies against CD19 and CD20. MCL patients frequently relapse. Complex pathogenesis and the management of patients with progression after treatment with BTK/Bcl2 inhibitors and CAR-T (triple-resistant MCL) remain a challenge. Next-generation clinical trials incorporating newer agents and concurrent translational and molecular investigations are ongoing. 1 | INTRODUCTION Mantle cell lymphoma (MCL) is an uncommon subtype of aggressive B cell non-Hodgkin's lymphoma (B-NHL). In 1982, Weisenburger et al. 1 first described 12 cases of malignant lymphoma with lymph node biopsies showing widened mantle zones around germinal centers in the secondary lymphoid follicles. The diagnosis of MCL 2 is now well characterized. MCL is no longer considered a single disease but is a mixed bag of various subcategories with a spectrum of molecular and clinical features. MCL patients have varied clinical presentations (generally symptomatic to an asymptomatic indolent clinical course).Advances in MCL research have significantly enhanced our understanding of pathogenesis, tumor microenvironment, 3 risk factor prognostication, 4 and molecular categories. 5 With the available treatment modalities (chemoimmunotherapy, 6 stem cell transplantation [SCT], 7 covalent and noncovalent BTK inhibitors, 8,9 bispecific antibodies, 10 an ROR1 drug conjugate, 11 and Bcl2 antagonists 12 ), the response rates and patient survival have improved. 13 The FDA approval of anti-CD19-chimeric antigen receptor therapy (CAR-T)-brexucabtagene autoleucel 14 -is a landmark

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Section: Introductionmentioning

confidence: 74%

Section: Prognostic Factorsmentioning

confidence: 83%

Mantle cell lymphoma in 2022—A comprehensive update on molecular pathogenesis, risk stratification, clinical approach, and current and novel treatments

Jain

Wang

2022

American J Hematol

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“…A previous retrospective study comparing the efficacy of R-bendamustine, R-CHOP, and MCL2 as frontline therapies showed similar age, ECOG, and MIPI class distribution in MCL2-treated patients. 10 We observed an increase in MIPI high-risk patients in the trial-ineligible group (37.7%), and the inclusion of ECOG 3-4 patients, showing that aggressive disease presentation is an important factor in selecting treatment strategies in clinical practice.…”

mentioning

confidence: 72%

“…Among trial‐ineligible patients, the median OS was also remarkable (9.8 years). Albertsson‐Linblad and colleagues 10 reported a median OS of 4.9 years in patients receiving any systemic therapy in the frontline and also showed that both MCL2 and RB are superior over R‐CHOP. We observed that the PFS improvement was greater in trial‐eligible patients than in trial‐ineligible patients (6.4 versus 4.4 years).…”

Section: Other Mcl2 Trial Eligible Trial Ineligible Clinical Mcl2 Trialmentioning

confidence: 99%

Real-world Data: MCL2 Protocol Demonstrates Excellent Treatment Results Among Patients With Mantle Cell Lymphoma Not Fulfilling the Original Trial Inclusion Criteria

Harmanen,

Klaavuniemi,

Sorigue

et al. 2023

HemaSphere

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Mantle cell lymphoma (MCL) is a rare and heterogeneous subgroup of B-cell lymphomas. The clinical course of MCL varies from an indolent form to an extremely aggressive phenotype. MCL is still an incurable disease. However, intensified chemoimmunotherapy regimens and targeted therapies have increased the overall survival (OS) of patients <65 years old from 5.6 years to 8.9 years. 1 Today, the standard treatment for fit patients <65-70 years is high-dose cytarabine-containing immunochemotherapy regimens followed by autologous stem cell transplantation (ASCT). 2 The MCL2 protocol developed by the Nordic Lymphoma Group is one of these approaches. 3,4 The MCL2 protocol has shown a median OS of 12.7 years at the 15-year follow-up and a median progression-free survival (PFS) of 8.5 years. 4 Similar results have been obtained in other high-dose regimen trials. [5][6][7] This study aimed to evaluate the efficacy of the MCL2 protocol in a population-based retrospective analysis and to compare treatment results in patients fulfilling the trial eligibility criteria with those who would have been trial ineligible.We collected data on patients diagnosed with MCL from 7 hospitals in Finland and 1 hospital in Spain from 2000 to 2020. This study was approved by the Finnish Social and Health Data Permit Authority. In total, 520 patients were included in this study. Of these, 198 patients (38%) received treatment according to the MCL2 protocol (the MCL2 group). The MCL2 protocol started with the induction treatment of rituximabmaxi-CHOP, alternating with rituximab-high-dose-cytarabine. ASCT, preceded by BEAM therapy (carmustine-etoposidecytarabine-melphalan), was used as a consolidation therapy after 6 immunochemotherapy cycles. 3 Rituximab maintenance therapy has been used as an option after ASCT in recent years. The remaining 322 patients (the other group) received rituximab combined with CHOP/CHOP-like regimens, bendamustine, or high-dose cytarabine-based regimens, MCL-FI (a Finnish protocol for elderly patients), 8 single-agent rituximab, or irradiation. To evaluate the impact of the patient selection criteria on survival, we divided the patients treated with the MCL2 protocol into trial-eligible and trial-ineligible subgroups, following the MCL2 trial inclusion criteria, which were an Eastern Cooperative Oncology Group (ECOG) performance test status of 0-2, stage II-IV disease, and age <66 years. 3 To obtain comparable groups, we excluded the patients with missing trial inclusion parameters in all categories. The patient-specific characteristics of the other group, the MCL2 group, and the subgroups of trial-eligible and trial-ineligible patients, along with the actual MCL2 trial, 3 are summarized in Table 1. The median age was higher in the trial-ineligible group (67 years) than in the trial-eligible group (59 years), and Mantle Cell Lymphoma International Prognostic Index (MIPI) high-risk disease was more common in the trial-ineligible group (37.7% versus 20.9%).The MCL subtype was not reported in most pathology reports; ther...

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“…25 In a real-world study of patients diag nosed in Sweden between 2007 and 2017, for patients under 70 years of age there was no sig nifi cant dif fer ence in OS with inten sified MCL2 pro to col or R-CHOP com pared to bendamustinerituximab. 31 Additionally, it may be pos si ble to con sider the defer ral of ASCT to the relapsed/refrac tory (R/R) set ting. There are data to sug gest that ASCT can be effec tive in CR2, although it is unclear whether out comes are equiv a lent to up-front ASCT.…”

Section: Clinical Casementioning

confidence: 99%

What is the role of up-front autologous stem cell transplantation in mantle cell lymphoma?

Kumar

2022

Hematology

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Up-front autologous stem cell transplantation (ASCT) is the established standard of care for younger, transplant-eligible MCL patients and is associated with a prolonged progression-free survival (PFS) benefit. However, there is no randomized controlled trial data, with therapy including rituximab and cytarabine, that has established a PFS and overall survival (OS) benefit with ASCT in the modern era. Multiple retrospective studies have failed to identify an OS benefit associated with ASCT in younger MCL patients. The high-risk patient subgroup with evidence of baseline TP53 mutation has a dismal outcome with intensive chemoimmunotherapy followed by ASCT, thus up-front ASCT is not optimal for this patient subset. Ongoing randomized clinical trials will help to clarify the role of up-front ASCT in the future. For example, the ongoing European MCL Network Triangle study incorporating ibrutinib into chemoimmunotherapy induction and maintenance with and without ASCT will help define the role of ASCT in the era of novel biologically targeted agents (ClinicalTrials.gov identifier: NCT02858258). Additionally, minimal residual disease (MRD) assessment is a powerful prognostic tool in MCL, and the ongoing Eastern Cooperative Oncology Group-American College of Radiology Imaging Network E4151 study is comparing maintenance rituximab alone vs ASCT consolidation in MCL patients who achieve remission and MRD-undetectable status post induction (ClinicalTrials.gov identifier: NCT03267433). ASCT remains a highly efficacious initial therapy for younger MCL patients; however, ultimately the decision to pursue ASCT requires discussion of risks vs benefits, incorporating patient preferences and values.

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Survival in mantle cell lymphoma after frontline treatment with R-bendamustine, R-CHOP and the Nordic MCL2 regimen – a real world study on patients diagnosed in Sweden 2007-2017

Abstract: Not available.

Cited by 12 publications

References 14 publications

Mantle cell lymphoma in 2022—A comprehensive update on molecular pathogenesis, risk stratification, clinical approach, and current and novel treatments

Mantle cell lymphoma in 2022—A comprehensive update on molecular pathogenesis, risk stratification, clinical approach, and current and novel treatments

Real-world Data: MCL2 Protocol Demonstrates Excellent Treatment Results Among Patients With Mantle Cell Lymphoma Not Fulfilling the Original Trial Inclusion Criteria

What is the role of up-front autologous stem cell transplantation in mantle cell lymphoma?

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