Lenalidomide plus bendamustine-rituximab does not overcome the adverse impact of <i>TP53</i> mutations in mantle cell lymphoma

Eskelund, Christian Winther; Albertsson-Lindblad, Alexandra; Kolstad, Arne; Laurell, Anna; Räty, Riikka; Pedersen, Lone Bredo; Geisler, Christian H.; Grønbæk, Kirsten

doi:10.3324/haematol.2018.194399

Cited by 17 publications

(16 citation statements)

References 16 publications

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“…In this study, there was no impact of age or gender on overall OS or progression free survival (PFS). Similarly, performance status, stage of disease, level of LDH at diagnosis or MIPI did not affect outcome in this cohort, 21 but the presence of a TP53 mutation was associated with significantly worse outcome 10 …”

Section: Introductionmentioning

confidence: 62%

“…Similarly, performance status, stage of disease, level of LDH at diagnosis or MIPI did not affect outcome in this cohort, 21 but the presence of a TP53 mutation was associated with significantly worse outcome. 10 The primary aim of this study was to explore HRQOL before, during and after chemotherapy in an older population of patients with previously untreated MCL in relation to a reference population and investigate its prognostic impact. Secondary aims were to identify predictors for HRQOL, information that may potentially be used for improvement in rehabilitation.…”

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confidence: 99%

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Pre‐treatment health‐related quality of life parameters have prognostic impact in patients >65 years with newly diagnosed mantle cell lymphoma: The Nordic Lymphoma Group MCL4 (LENA‐BERIT) experience

Lindberg

Eskelund

Albertsson-Lindblad

et al. 2021

Hematological Oncology

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Mantle cell lymphoma (MCL) is a rare, often aggressive type of B‐cell lymphoma with poor survival and no cure. Cancer and cancer treatment has a negative impact on health‐related quality of life (HRQOL) both during active disease and in the long term, and improvement of HRQOL is a crucial objective of cancer therapy in older patients and no curative intent. Baseline HRQOL has in other lymphoma populations been shown to be predictive of outcome. Here, we explored HRQOL, and its association with survival, by the EORTC QLQ‐C30 questionnaire, before, during and after chemotherapy in a patient cohort with MCL, treated within the NLG‐MCL4 trial, designed to evaluate the addition of lenalidomide (LEN) to rituximab‐bendamustine (R‐B) as first‐line treatment. Fifty‐one patients were enrolled, median age was 71 years (range 62–84), 37 were men (73%). Pre‐treatment HRQOL was similar to scores from the reference population with healthy individuals. During treatment, HRQOL deteriorated, but reverted to the same level as the reference population after treatment. There was a correlation between physical function (p = 0.001) and role function (p = 0.006) at baseline and WHO performance status, but not with other clinical or genetic prognostic factors. None of the baseline factors were predictive for treatment related to HRQOL in this cohort. Pre‐treatment physical (p = 0.011) and role function (p = 0.032) were independent factors associated with overall survival, and physical function (p = 0.002) was also associated with progression free survival. These findings may possibly be used to design support during treatment and improve rehabilitation. Further investigations are needed for assessment of long‐term HRQOL.

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Section: Introductionmentioning

confidence: 62%

mentioning

confidence: 99%

Pre‐treatment health‐related quality of life parameters have prognostic impact in patients >65 years with newly diagnosed mantle cell lymphoma: The Nordic Lymphoma Group MCL4 (LENA‐BERIT) experience

Lindberg

Eskelund

Albertsson-Lindblad

et al. 2021

Hematological Oncology

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“…Several studies into MCL have demonstrated the association of TP53 mutations with poor clinical outcomes 11,43 . TP53 alterations were previously associated with a poor prognosis in MCL patients treated with standard treatment modalities 44,45 . A recent study suggested that allogeneic hematopoietic cell transplantation may be a beneficial treatment option for patients with TP53 mutations 46 .…”

Section: Discussionmentioning

confidence: 94%

Genetic heterogeneity and prognostic impact of recurrent ANK2 and TP53 mutations in mantle cell lymphoma: a multi-centre cohort study

Jeong

Park

Yun

et al. 2020

Sci Rep

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The molecular features of mantle cell lymphoma (MCL), including its increased incidence, and complex therapies have not been investigated in detail, particularly in East Asian populations. In this study, we performed targeted panel sequencing (TPS) and whole-exome sequencing (WES) to investigate the genetic alterations in Korean MCL patients. We obtained a total of 53 samples from MCL patients from five Korean university hospitals between 2009 and 2016. We identified the recurrently mutated genes such as SYNE1, ATM, KMT2D, CARD11, ANK2, KMT2C, and TP53, which included some known drivers of MCL. The mutational profiles of our cohort indicated genetic heterogeneity. The significantly enriched pathways were mainly involved in gene expression, cell cycle, and programmed cell death. Multivariate analysis revealed that ANK2 mutations impacted the unfavourable overall survival (hazard ratio [HR] 3.126; P = 0.032). Furthermore, TP53 mutations were related to worse progressionfree survival (HR 7.813; P = 0.043). Among the recurrently mutated genes with more than 15.0% frequency, discrepancies were found in only 5 genes from 4 patients, suggesting comparability of the TPS to WES in practical laboratory settings. We provide the unbiased genetic landscape that might contribute to MCL pathogenesis and recurrent genes conferring unfavourable outcomes. Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin's lymphoma (NHL) accounting for 5-7% of all NHLs 1. Although MCL is uncommon (0.64/100,000 person-years), there has been a 130.9% rise in its incidence in recent years 2. Higher incidence rates have been seen in Caucasians (153.0%), Asians (96.

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“…The prognostic role of SOX11 is not well‐established, with different studies showing different conclusions . TP53 mutation has been identified a prognostic factor that predicts poor outcome in MCL patients . However, the mutation status of TP53 is not routinely examined in most pathology laboratories.…”

Section: Discussionmentioning

confidence: 99%

Association of red blood cell distribution width and outcomes in patients with mantle cell lymphoma

et al. 2019

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Red blood cell distribution width (RDW), which measures the range of variation of red blood cell volume, has been explored as a prognostic factor in multiple types of cancer. However, the role of RDW in mantle cell lymphoma (MCL), a rare type of non‐Hodgkin lymphoma with poor outcomes, remains to be determined. Therefore, we investigated the prognostic role of RDW in MCL. We found that 21 of 76 MCL patients (27.6%) had an abnormally elevated RDW (>15.7%). Abnormally elevated RDW was significantly associated with presence of B symptoms (P = 0.0020), elevated lactate dehydrogenase (LDH) (P = 0.0010), higher leukocyte count (P = 0.0345), higher simplified Mantle Cell International Prognostic Index (sMIPI) (P = 0.0194), and lower level of hemoglobin (Hb) (P < 0.0001). It was marginally associated with increased C‐reactive protein (P = 0.0862). RDW was significantly correlated with Hb level (r2 = 0.42) and LDH level (r2 = 0.19). 15.8% was determined as the best cutoff of RDW in predicting the survival outcome by the X‐tile software. Survival analysis revealed that high RDW (>15.8%) predicted shorter progression‐free survival (PFS) (hazards ratio [HR]: 3.14; P = 0.0005) and shorter overall survival (OS) (HR: 4.04; P < 0.0001). High RDW independently predicted both shorter PFS (P = 0.0493) and OS (P = 0.0118). RDW also improved the prognostic stratification based on sMIPI. In conclusion, our study identified RDW as a novel prognostic factor of clinical feasibility in the prognostication of MCL.

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Lenalidomide plus bendamustine-rituximab does not overcome the adverse impact of TP53 mutations in mantle cell lymphoma

Cited by 17 publications

References 16 publications

Pre‐treatment health‐related quality of life parameters have prognostic impact in patients >65 years with newly diagnosed mantle cell lymphoma: The Nordic Lymphoma Group MCL4 (LENA‐BERIT) experience

Pre‐treatment health‐related quality of life parameters have prognostic impact in patients >65 years with newly diagnosed mantle cell lymphoma: The Nordic Lymphoma Group MCL4 (LENA‐BERIT) experience

Genetic heterogeneity and prognostic impact of recurrent ANK2 and TP53 mutations in mantle cell lymphoma: a multi-centre cohort study

Association of red blood cell distribution width and outcomes in patients with mantle cell lymphoma

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