Minimal residual disease in mantle cell lymphoma: insights into biology and impact on treatment

Hoster, Eva; Pott, Christiane

doi:10.1182/asheducation-2016.1.437

Cited by 43 publications

(32 citation statements)

References 36 publications

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“…This study demonstrated that rituximab maintenance can improve survival after SCT. MRD assessment in MCL has not been systematically implemented in clinical practice; however, a few studies have shown the critical clinical significance of MRD‐positive disease status and risk of predicting future relapses . Another issue for MRD assessment in MCL is optimization of the technique according to the tissue type used to test MRD, as not all patients have bone marrow involvement at diagnosis and not all patients have peripheral blood lymphocytosis sufficient enough for testing MRD by either flow cytometry or PCR (allele specific quantitative oligonucleotide polymerase chain reaction).…”

Section: Advances In the Treatment Of MCLmentioning

confidence: 99%

Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management

2019

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Unprecedented advances in our understanding of the pathobiology, prognostication, and therapeutic options in mantle cell lymphoma (MCL) have taken place in the last few years. Heterogeneity in the clinical course of MCL—indolent vs aggressive—is further delineated by a correlation with the mutational status of the variable region of immunoglobulin heavy chain, methylation status, and SOX‐11 expression. Cyclin‐D1 negative MCL, in situ MCL neoplasia, and impact of the karyotype on prognosis are distinguished. Apart from Ki‐67% and morphology pattern (classic vs blastoid/pleomorphic), the proliferation gene signature has helped to further refine prognostication. Studies focusing on mutational dynamics and clonal evolution on Bruton's tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib) and/or Bcl2 antagonists (venetoclax) have further clarified the prognostic impact of somatic mutations in TP53, BIRC3, CDKN2A, MAP3K14, NOTCH2, NSD2, and SMARCA4 genes. In therapy, long‐term follow‐up on chemo‐immunotherapy studies has demonstrated durable remissions in some patients; however, long‐term toxicities, especially from second cancers, are a serious concern with chemotherapy. The therapeutic options in MCL are constantly evolving, with dramatic responses from nonchemotherapeutic agents (ibrutinib, acalabrutinib, and venetoclax). Chimeric antigen receptor therapy and combinations of nonchemotherapeutic agents are actively being studied and our focus is shifting toward making the treatment of MCL chemotherapy‐free. Still, MCL remains incurable. The following aspects of MCL continue to pose a challenge: disease transformation, role of the cytokine‐microenvironmental milieu, incorporation of positron emission tomography‐computerized tomography imaging, minimal residual disease in the prognosis, circulating tumor DNA testing for clonal evolution, predicting resistance to BTK inhibitors, and optimal management of patients who progress on BTK/Bcl2 inhibitors. Next‐generation clinical trials should incorporate nonchemotherapeutic agents and personalize the treatment based upon the genomic profile of individual patient. Recent advances in the field of MCL are reviewed.

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Section: Advances In the Treatment Of MCLmentioning

confidence: 99%

Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management

2019

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“…In recent years, MRD assessment after induction has emerged as an invaluable posttreatment prognostication tool . Despite the fact that most of the so far published studies confirmed predictive significance of achieving MRD negativity after induction, we did not find a single published manuscript in MCL patients that would include MRD assessment in the context of RM therapy only.…”

Section: Discussionmentioning

confidence: 78%

“…Landmark European MCL Network study demonstrated significant survival benefit of RM over observation or interferon alpha . Persistent minimal residual disease (MRD) after induction has been repeatedly associated with imminent clinical relapse and a shorter progression free and overall survival (PFS, OS) . Despite the fact that most of the so far published studies confirmed prognostic significance of MRD after induction, we did not find a single published MCL study that would include RM.…”

Section: Introductionmentioning

confidence: 87%

Potential loss of prognostic significance of minimal residual disease assessment after R‐CHOP‐based induction in elderly patients with mantle cell lymphoma in the era of rituximab maintenance

Klener

Froňková

Kalinová

et al. 2018

Hematological Oncology

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Rituximab maintenance (RM) prolongs survival of elderly patients with mantle cell lymphoma (MCL). Persistent minimal residual disease (MRD) after induction repeatedly correlated with shorter progression-free survival (PFS). However, none of the published studies analyzed patients treated with RM. The main purpose was to analyze prognostic significance of MRD in the elderly patients with newly diagnosed MCL treated according to the recently published observational trial protocol (alternation of R-CHOP and R-cytarabine, 3 + 3 cycles, GovTrial number NCT03054883) at the centers that implemented RM. Minimal residual disease was evaluated by a EuroMRD standardized real-time PCR approach after 3 and 6 cycles of the induction therapy. Prognostic significance of MRD was analyzed in a subcohort of patients treated at the centers that implemented RM as a standard approach. Bone marrow proved to be a significantly more sensitive source for MRD detection than peripheral blood. In either compartment MRD (positive versus negative) after 3 or 6 cycles of the induction therapy did not correlate with PFS. The observed loss of prognostic significance of MRD after the R-CHOP-based induction appears to be a consequence of RM immune control over the residual lymphoma.

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“…Recurrence of disease is believed to be due to persistence of a relatively small number of lymphoma cells that are below detection level of clinically employed response-evaluation methods. This notion is supported by observations that newer, more sensitive techniques like multicolor flow cytometry (FCM) or polymerase chain reaction (PCR) are able to detect such residual cell population (referred to as minimal residual disease [MRD]) in some NHL patients who are otherwise in CR post completion of therapy [8,9]. MRD cells carry the same phenotypic and genetic markers as the original lymphoma as detected by FCM and PCR.…”

Section: Research Papermentioning

confidence: 93%

Isolation and characterization of a CD34+ sub-clone in B-cell lymphoma

et al. 2020

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Non-Hodgkin's lymphoma (NHL) is the most common hematological malignancy in the US. Many types remain incurable despite response to initial therapy and achievement of complete remission (CR). Advanced laboratory techniques like multicolor flow cytometry (FCM) and polymerase chain reaction (PCR) have demonstrated persistence of rare malignant cell population post therapy. However, the functional and biological characteristics of this population have not been elucidated. Established B-lymphoma cell lines (B-NHL) and patient-derived samples (PDS) were analyzed using 8-color FCM. CD34 + sub-population was enriched using in vitro exposure to 2-chlorodeoxyadenosine (2-CdA) and by CD34 magnetic beads. Genetic analysis of cell fractions was done by karyotyping and array comparative genomic hybridization (aCGH). Sensitivity to chemotherapy was assayed by short-term in vitro exposure to chemotherapy. Clonogenicity was determined by soft agar colony formation assay, and proliferation was determined using DNA staining with propidium iodide and FCM. FCM demonstrated the presence of a minute sub-clone of monotypic B-cells that express CD34 in B-NHL cell lines (3 of 3) and in PDS (8 of 8). This sub-population enriched up to 50 fold in vitro by exposure to 2-CdA and up to 80% purity by CD34 magnetic bead column isolation. Except for CD34 expression, this population expressed identical phenotype and genotype to parent cells, but was more proliferative, Hoechst 33342-positive, clonogenic, and resistant to chemotherapy compared with the CD34population. The isolated CD34 + monotypic B-cells may contribute to resistance of certain NHL to treatment and should be targeted by potential new drugs for NHL.

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Minimal residual disease in mantle cell lymphoma: insights into biology and impact on treatment

Cited by 43 publications

References 36 publications

Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management

Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management

Potential loss of prognostic significance of minimal residual disease assessment after R‐CHOP‐based induction in elderly patients with mantle cell lymphoma in the era of rituximab maintenance

Isolation and characterization of a CD34+ sub-clone in B-cell lymphoma

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