Minimal residual disease (MRD) in mantle cell lymphoma

Ladetto, Marco; Tavarozzi, Rita; Pott, Christiane

doi:10.21037/aol-2018-mcl-009

Cited by 6 publications

(4 citation statements)

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“…MRD assessments were available for only 28 of 37 patients. We used qualitative flow cytometry for MRD assessment that requires a high level of expertise and is not standardized across institutions; it also has a lower sensitivity as compared to PCR‐based or high‐throughput sequencing‐based MRD assessments 26 . On the other hand, flow cytometry MRD testing does not require patient‐specific PCR primers, has a rapid turnaround time, and did demonstrate a high level of applicability (80%‐90% positivity at baseline) and clinical significance (MRD negativity after 2 cycles was associated with prolonged PFS).…”

Section: Discussionmentioning

confidence: 99%

Ofatumumab plus HyperCVAD/HD‐MA induction leads to high rates of minimal residual disease negativity in patients with newly diagnosed mantle cell lymphoma: Results of a phase 2 study

Torka

Akhtar

Reddy

et al. 2022

Cancer

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BACKGROUND:Ofatumumab is a humanized type 1 anti-CD20 monoclonal antibody. Preclinical studies show improved complementmediated cytotoxicity (CMC) compared to rituximab in mantle cell lymphoma (MCL). This study evaluates the safety and efficacy of combining ofatumumab with HyperCVAD/MA (O-HyperCVAD) in newly diagnosed MCL. METHODS: In this single-arm phase 2 study, 37 patients were treated with the combination of O-HyperCVAD for 4 or 6 cycles, followed by high dose chemotherapy and autologous stem cell transplant. Primary objectives were overall response rate (ORR) and complete response (CR) rate at the end of therapy. Secondary objectives included minimal residual disease (MRD) negativity, progression-free survival (PFS), and overall survival (OS). RESULTS: Median age was 60 years; ORR was 86% and 73% achieved a CR by modified Cheson criteria. The MRD negativity rate was 78% after 2 cycles of therapy, increasing to 96% at the end of induction; median PFS and OS were 45.5 months and 56 months, respectively. Achieving a post-induction CR by both imaging and flow cytometry was associated with improved PFS and OS. Early MRD negativity (post-2 cycles) was also associated with an improved PFS but not OS. There were 3 deaths while on therapy, and grades 3 and 4 adverse events (AEs) were observed in 22% and 68% of the patients. CONCLUSION: The addition of ofatumumab to HyperCVAD/HD-MA led to high rates of MRD negativity by flow cytometry in patients with newly diagnosed MCL. Achieving a CR post-induction by both imaging and flow cytometry is associated with improved overall survival.

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Section: Discussionmentioning

confidence: 99%

Ofatumumab plus HyperCVAD/HD‐MA induction leads to high rates of minimal residual disease negativity in patients with newly diagnosed mantle cell lymphoma: Results of a phase 2 study

Torka

Akhtar

Reddy

et al. 2022

Cancer

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“…However, effective therapy for patients with relapsed MCL with ibrutinib resistance, aggressive form of the disease, and/or transplant ineligible patients represents an important unmet medical need [ 8 , 34 ]. Minimal residual disease (MRD) has been increasingly investigated in MCL [ 35 ]. The potentially valuable use of MRD as a surrogate end point for progression-free survival in comparing the efficacy of different treatments in randomized trials is also still hampered by limitations in take-up in clinical routine, partly because of the need for patient-specific primers and standardization [ 36 ].…”

Section: Situation Reportmentioning

confidence: 99%

Tackling Mantle Cell Lymphoma in Europe

Horgan¹,

Walewski

Aurer

et al. 2022

Healthcare

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An expert panel convened by the European Alliance for Personalized Medicine (EAPM) reflected on achievements and outstanding challenges in Europe in mantle cell lymphoma (MCL). Through the prism of member state experience, the panel noted advances in outcomes over the last decade, but highlighted issues constituting barriers to better care. The list notably included availability of newer treatments, infrastructure and funding for related testing, and shortages of relevant skills and of research support. The prospect of improvements was held to reside in closer coordination and cooperation within and between individual countries, and in changes in policy and scale of investment at both national and EU levels.

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“…1 The detection of minimal residual disease (MRD) allows a highly sensitive longitudinal monitoring of tumor load and residual disease during and after treatment in different mature B-cell malignancies such as MCL, 11 chronic lymphocytic leukemia, 12 and follicular lymphoma (FL). 13 Importantly, MRD assessment has been standardized 14 and is nowadays established as a routine tool to guide treatment in ALL. 15 The European MCL Elderly trial (ClinicalTrials.gov identifier: NCT00209209) was an international, double-randomized phase III trial that established R-maintenance in older patients with MCL responding to first-line rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) on the basis of prolonged progression-free survival (PFS) and overall survival (OS).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Predictive Value of Minimal Residual Disease for Efficacy of Rituximab Maintenance in Mantle Cell Lymphoma: Results From the European Mantle Cell Lymphoma Elderly Trial

Hoster,

Delfau-Larue,

Macintyre

et al. 2024

JCO

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PURPOSE The outcome of older patients with mantle cell lymphoma (MCL) has improved by the introduction of immunochemotherapy, followed by rituximab (R)-maintenance. Assessment of minimal residual disease (MRD) represents a promising tool for individualized treatment decisions and was a prospectively planned part of the European MCL Elderly trial. We investigated how MRD status influenced the efficacy of R-maintenance and how MRD can enable tailored consolidation strategies. PATIENTS AND METHODS Previously untreated patients with MCL age 60 years or older have been randomly assigned to R versus interferon-alpha maintenance after response to rituximab, fludarabine, cyclophosphamide (R-FC) versus rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP). MRD monitoring was performed by real-time quantitative polymerase chain reaction (qPCR) following EuroMRD guidelines. RESULTS A qPCR assay with a median sensitivity of 1 × 10−5 could be generated in 80% of 288 patients in an international, multicenter, multilaboratory setting. More extensive tumor dissemination facilitated the identification of a molecular marker. The efficacy of R-maintenance in clinical remission was confirmed for MRD-negative patients at the end of induction in terms of progression-free survival (PFS; hazard ratio [HR], 0.38 [95% CI, 0.21 to 0.63]) and overall survival (OS; HR, 0.37 [95% CI, 0.20 to 0.68]), particularly in R-CHOP–treated patients (PFS-HR, 0.23 [95% CI, 0.10 to 0.52]; OS-HR, 0.19 [95% CI, 0.07 to 0.52]). R-maintenance appeared less effective in MRD-positive patients (PFS-HR, 0.51 [95% CI, 0.26 to 1.02]) overall and after R-CHOP induction (PFS-HR, 0.59 [95% CI, 0.28 to 1.26]). R-FC achieved more frequent and faster MRD clearance compared with R-CHOP. MRD positivity in clinical remission after induction was associated with a short median time to clinical progression of approximately 1-1.7 years. CONCLUSION The results confirm the strong efficacy of R-maintenance in patients who are MRD-negative after induction. Treatment de-escalation for MRD-negative patients is discouraged by our results. More effective consolidation strategies should be explored in MRD-positive patients to improve their long-term prognosis.

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Minimal residual disease (MRD) in mantle cell lymphoma

Cited by 6 publications

References 0 publications

Ofatumumab plus HyperCVAD/HD‐MA induction leads to high rates of minimal residual disease negativity in patients with newly diagnosed mantle cell lymphoma: Results of a phase 2 study

Ofatumumab plus HyperCVAD/HD‐MA induction leads to high rates of minimal residual disease negativity in patients with newly diagnosed mantle cell lymphoma: Results of a phase 2 study

Tackling Mantle Cell Lymphoma in Europe

Predictive Value of Minimal Residual Disease for Efficacy of Rituximab Maintenance in Mantle Cell Lymphoma: Results From the European Mantle Cell Lymphoma Elderly Trial

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