scholarly journals Bendamustine and rituximab as induction therapy in both transplant-eligible and -ineligible patients with mantle cell lymphoma

2020 ◽  
Vol 4 (15) ◽  
pp. 3486-3494
Author(s):  
Diego Villa ◽  
Laurie H. Sehn ◽  
Kerry J. Savage ◽  
Cynthia L. Toze ◽  
Kevin Song ◽  
...  
Keyword(s):  
High Risk ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
First Line ◽  
Ki 67 ◽  
Historical Cohort ◽  
Entire Cohort ◽  
Mantle Cell

Abstract Rituximab-containing chemotherapy regimens constitute standard first-line therapy for mantle cell lymphoma (MCL). Since June 2013, 190 patients ≥18 years of age with MCL in British Columbia have been treated with bendamustine and rituximab (BR). The overall response rate to BR was 88% (54% complete response). Of these, 61 of 89 patients (69%) aged ≤65 years received autologous stem cell transplantation and 141 of 190 patients (74%) from the entire cohort received maintenance rituximab. Twenty-three patients (12%) had progressive disease, associated with high risk per the Mantle Cell Lymphoma International Prognostic Index (MIPI), Ki-67 ≥50%, and blastoid/pleomorphic histology. Outcomes were compared with a historical cohort of 248 patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; January 2003 to May 2013). Treatment with BR was associated with significant improvements in progression-free survival (PFS), but not overall survival (OS), compared with R-CHOP in the whole cohort (3-year PFS, 66% BR vs 51% R-CHOP, P = .003; 3-year OS, 73% BR vs 66% R-CHOP, P = .054) and in those >65 years of age (3-year PFS, 56% BR vs 35% R-CHOP, P = .001; 3-year OS, 64% BR vs 55% R-CHOP, P = .063). Outcomes in transplanted patients were not statistically significantly different compared with R-CHOP (3-year PFS, 85% BR vs 76% R-CHOP, P = .135; 3-year OS, 90% BR vs 88% R-CHOP, P = .305), although in multivariate analyses, treatment with BR was associated with improved PFS (hazard ratio, 0.40 [95% confidence interval, 0.17-0.94]; P = .036) but not OS. BR is an effective first-line option for most patients with MCL, however, outcomes are suboptimal for those with high-risk features and further studies integrating novel agents are warranted.

The Mantle Cell Lymphoma International Prognostic Index (MIPI) is superior to the International Prognostic Index (IPI) in predicting survival following intensive first-line immunochemotherapy and autologous stem cell transplantation (ASCT)

Blood ◽  
2010 ◽  
Vol 115 (8) ◽  
pp. 1530-1533 ◽  
Author(s):  
Christian H. Geisler ◽  
Arne Kolstad ◽  
Anna Laurell ◽  
Riikka Räty ◽  
Mats Jerkeman ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Autologous Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
First Line ◽  
Mantle Cell

Abstract Mantle cell lymphoma (MCL) has a heterogeneous clinical course. The recently proposed Mantle Cell Lymphoma International Prognostic Index (MIPI) predicted the survival of MCL better than the International Prognostic Index in MCL patients treated with conventional chemotherapy, but its validity in MCL treated with more intensive immunochemotherapy has been questioned. Applied here to 158 patients of the Nordic MCL2 trial of first-line intensive immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation, the MIPI and the simplified MIPI (s-MIPI) predicted survival significantly better (P < .001) than the International Prognostic Index (P > .004). Both the MIPI and the s-MIPI mainly identified 2 risk groups, low and intermediate versus high risk, with the more easily applied s-MIPI being just as powerful as the MIPI. The MIPIB (biological), incorporating Ki-67 expression, identified almost half of the patients as high risk. We suggest that also a simplified MIPIB is feasible. This trial was registered at www.isrctn.org as #ISRCTN 87866680.

MicroRNA Signature Obtained From the Comparison of Aggressive With Indolent Non-Hodgkin Lymphomas: Potential Prognostic Value in Mantle-Cell Lymphoma

2013 ◽  
Vol 31 (23) ◽  
pp. 2903-2911 ◽  
Author(s):  
Rashmi S. Goswami ◽  
Eshetu G. Atenafu ◽  
Yali Xuan ◽  
Levi Waldron ◽  
Patricia P. Reis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mantle Cell Lymphoma ◽  
Prognostic Model ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Differentially Expressed ◽  
Training Set ◽  
Ki 67 ◽  
Mantle Cell

Purpose Mantle-cell lymphoma (MCL) has a variable natural history but is incurable with current therapies. MicroRNAs (miRs) are useful in prognostic assessment of cancer. We determined an miR signature defining aggressiveness in B-cell non-Hodgkin lymphomas (NHL) and assessed whether this signature aids in MCL prognosis. Methods We assessed miR expression in a training set of 43 NHL cases. The miR signature was validated in 44 additional cases and examined on a training set of 119 MCL cases from four institutions in Canada. miRs significantly associated with overall survival were examined in an independent cohort of 114 MCL cases to determine association with patient outcome. miR expression was combined with current clinical prognostic factors to develop an enhanced prognostic model in patients with MCL. Results Fourteen miRs were differentially expressed between aggressive and indolent NHL; 11 of 14 were validated in an independent set of NHL (excluding MCL). miR-127-3p and miR-615-3p were significantly associated with overall survival in the MCL training set. Their expression was validated in an independent MCL patient set. In comparison with Ki-67, expression of these miRs was more significantly associated with overall survival among patients with MCL. miR-127-3p was combined with Ki-67 to create a new prognostic model for MCL. A similar model was created with miR-615-3p and Mantle Cell Lymphoma International Prognostic Index scores. Conclusion Eleven miRs are differentially expressed between aggressive and indolent NHL. Two novel miRs were associated with overall survival in MCL and were combined with clinical prognostic models to generate novel prognostic data for patients with MCL.

scholarly journals Prognostic significance of p53, Sox11, and Pax5 co-expression in mantle cell lymphoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Caixia Jing ◽  
Yuhuan Zheng ◽  
Yu Feng ◽  
Xia Cao ◽  
Caigang Xu
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Tissue Array ◽  
Ki 67 ◽  
Mutation Status ◽  
Mantle Cell

AbstractMantle cell lymphoma (MCL) is a relatively rare subtype of non-Hodgkin’s lymphoma. To identify molecular biomarkers in MCL, we performed immunohistochemistry tissue arrays using biopsies from 64 MCL patients diagnosed in West China Hospital from 2012 to 2016. TP53 mutation status in those patients was also examined by sequencing. The sequencing results showed TP53 mutations were highly heterogeneous in MCL. We identified four novel TP53 mutations in MCL: P151R, G199R, V218E, and G325R. The MCL patients with TP53 mutations had inferior progression-free survival (PFS, p = 0.002) and overall survival (OS, p = 0.011). Tissue array results showed the expression of p53, Sox11, or Pax5 alone did not correlate with the patient PFS and OS. However, the MCL patients with triple-positive expression of p53/Sox11/Pax5 had inferior PFS (p = 0.008) and OS (p = 0.002). Such risk stratification was independent to the mantle cell lymphoma international prognostic index (MIPI), Ki-67 value, and TP53 mutation status of the patients. The triple-positive patients might represent a subtype of high-risk MCL. Our findings might indicate a novel way to stratify MCL and predict patients’ prognosis.

scholarly journals Nomogram incorporating clinicopathological parameters to predict the survival of patients with mantle cell lymphoma

2018 ◽  
Vol 67 (2) ◽  
pp. 331-337
Author(s):  
Yuandong Zhu ◽  
Wenxian Xu ◽  
Xiao Zheng ◽  
Zhuojun Zheng
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
White Cell Count ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Scoring Systems ◽  
Clinicopathological Parameters ◽  
Predictive Capacity ◽  
Ki 67 ◽  
Mantle Cell

This study intended to present a practicable prognostic nomogram for patients with mantle cell lymphoma (MCL). The clinical data of 281 patients were reviewed. A nomogram that could predict overall survival (OS) was constructed based on the Cox proportional hazard model. To compare the capacity of the nomogram with the International Prognostic Index (IPI) and MCL International Prognostic Index (MIPI) scoring systems, we used the concordance index (C-index) to validate the veracity and the calibration curve. Age, Eastern Cooperation Oncology Group, lactate dehydrogenase, white cell count and Ki-67 were independent prognostic factors in the multivariate analysis and were subsequently included in the nomogram construction. The C-index was 0.81 and 0.79 in the primary and validation cohorts, respectively, which were superior to the predictive capacity of the IPI and MIPI systems in both cohorts. The nomogram makes it possible for physicians to predict patient OS individually and correctly, but certain limitations are noted.

Mantle Cell Lymphoma International Prognostic Score Is Valid and Confirmed in Unselected Cohort of Patients Treated in Rituximab Era

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3745-3745 ◽  
Author(s):  
David Salek ◽  
Ingrid Vasova ◽  
Robert Pytlik ◽  
David Belada ◽  
Tomas Papajik ◽  
...  
Keyword(s):  
High Risk ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Prognostic Index ◽  
Low Risk ◽  
Intermediate Risk ◽  
First Line ◽  
Mantle Cell ◽  
Unselected Cohort

Abstract Introduction: Mantle cell lymphoma (MCL) is considered to be an incurable disease with a poor prognosis, but the prognosis can be significantly different among the patients. The new prognostic index MIPI (MCL International Prognostic Index) has been proposed recently (Hoster ASH 2006, Blood 2008). Three prognostic groups with different survival (low-risk, intermediate-risk and high-risk) can been identified, based on four variables: WBC count, ECOG performance status, LDH and age. Aim: To validate MIPI on an independent unselected cohort of newly diagnosed patients with MCL in the Czech Lymphoma Study Group (CLSG) registry. Methods and patients: Out of 293 patients with MCL diagnosed and registered in the period 1999–2007, 149 patients had central pathology review and confirmation of MCL diagnosis and were eligible for the analysis. The age median was 65 year (24–86), 63% were male (M:F ratio 1,7:1). Most of patients were diagnosed in advanced Ann Arbor stage IV (82%), limited stages I+II formed only 10,5%. The bone marrow was involved in 75% of cases. B-symptoms were present in 45% patients, LDH level elevated in 51%, poor performance status (ECOG 2–4) in 21% and the median leukocyte count was 7,9 ×109/L. A chemotherapy was used as a first line treatment in 144 patients, the combination with rituximab (R) in 106 ones (73%). The most used regimens were hyperCVAD/MTX-HDaraC (30x), R-CHOP (30x), CHOP (19x), R-FC (13x), then R-maxiCHOP/HDaraC (12x), R-CHOP/HDaraC (9x), COP (8x) and others. A consolidation of the first remission with high-dose chemotherapy and autologous stem cell transplantation was used in 12 patients, and an allogeneic transplantation in 2 patients. A first-line radiotherapy was used in 14 patients. Median follow-up is 31 months. Results: Median overall survival (OS) in the whole group of confirmed MCL patients was 58 months, median progression-free survival (PFS) was 24 months. The MIPI index can be calculated for 148 patients, 28% of them belong to low-risk (LR), 35% to intermediate-risk (IR) and 37% to high risk (HR) group. All clinical stages were included. Our comparison of survival curves according to MIPI risk groups confirms a different prognosis – the median OS in the LR group was not reached, in the IR group is the median OS 58 months, and in the HR group 25 months (p < 0,0001). The 3-year OS probability for LR, IR and HR group is 82%, 62% and 31%, resp. Similarly, median PFS in the LR, IR and HR group is 45, 24 and 13 months, resp. (p < 0,0001). The analysis of rituximab-treated subgroup was performed as well, with a significant difference between the three groups regarding to OS and PFS. The 3y OS probability for LR, IR and HR group is 82%, 63% and 37%, the median OS for LR and IR was not reached, for HR is 31 months (p<0.05). The median PFS in LR group was not reached (with 3y PFS probability 70%), in IR and HR group the median is 27 and 17 months, resp. (p<0.01). Conclusion: Our retrospective analysis confirms a validity of the MIPI prognostic model even in a non-selected population of patients with MCL. This prognostic index seems to be valid also in the era of rituximab. Figure Figure

Validation of the Mantle Cell Lymphoma Prognostic Index (MIPI): A Valuable Tool for Risk Stratification in Mantle Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2703-2703
Author(s):  
Stephen Douglas Smith ◽  
Eric D. Hsi ◽  
Brian J. Bolwell ◽  
Amanda Maggiotto ◽  
Meagan Effinger ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Stratification ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Performance Status ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
High Risk Group ◽  
Ecog Performance Status ◽  
Mantle Cell

Abstract Abstract 2703 Poster Board II-679 Introduction: Mantle cell lymphoma (MCL) is an incurable disease with a highly variable course. Improvements in therapy have been impeded by the lack of a universal prognostic model, making risk stratification and comparisons across clinical trials difficult. The International Prognostic Index (IPI) and Follicular Lymphoma International Prognostic Index (FLIPI) have been applied but show limitations in MCL, especially in distinguishing low and intermediate-risk patients (pts). The MIPI (Mantle Cell International Prognostic Index) was developed to overcome these limitations, and is based on WBC, age, and LDH (analyzed as continuous variables) and ECOG performance status.1 However, the MIPI has yet to be independently validated, and failed to predict outcome of MCL pts treated with Hyper-CVAD.2 To examine the prognostic capacity of the MIPI, we reviewed outcomes of pts diagnosed with MCL from 1998–2008 at the Cleveland Clinic Taussig Cancer Institute (CCTCI). Methods: Cases of MCL diagnosed at CCTCI were identified from our pathology database, yielding 85 unique pts. These subjects were retrospectively analyzed with approval of our Institutional Review Board. A total of 48 pts with advanced stage disease who underwent immediate treatment (within 90 days of diagnosis), and for whom adequate data for assignment of both MIPI and IPI existed, were the subject of review. Survival was identified from medical records and confirmed using a public social security database. Outcomes were compared using log-rank analysis of Kaplan-Meier survival analyses, and MIPI was calculated in accordance with the initial publication.1 Results: Pt characteristics at diagnosis were: median age 62 (range 39–85), 73% male, 75% ECOG performance status of 0-1, 96% stage IV disease, 52% elevated LDH, and 40% had extranodal involvement other than bone marrow (23% with GI involvement). Six pts had the blastoid variant of MCL. IPI scores at diagnosis were as follows: low (17%)/ low-intermediate (31%)/ high-int (25%)/ high (27%). MIPI scores at diagnosis were: low (33%) / int (25%)/ high(42%). Initial treatment included an anthracycline in 71% and rituximab in 60%. HyperCVAD was given 33%, and 23% underwent upfront (CR1/PR1) autologous transplantation. Median follow-up of survivors is 5.7 years. Median OS and RFS for all pts is 3.9 and 2.5 years, respectively. The IPI distinguished low and high-risk groups, but low-int and high-int groups were closely approximated (Figure 1). On the other hand, the MIPI distinguished 3 separate groups (Figure 2), including a high risk group with a 5-year survival of 11%. The MIPI maintained its prognostic capacity even in HyperCVAD-treated pts (log rank p=.01 for low/int/high MIPI among 16 pts, figure not shown.) The use of regimens including rituximab was not associated with improved OS (log rank p=0.21, comparing rituximab at any time vs none, figure not shown). Conclusions: Based on long-term follow-up of 48 pts diagnosed with MCL at CCTCI from 1998–2008, we verified the accuracy and ease of application of the MIPI for determining prognosis in MCL. On further analysis, rituximab did not impact OS of MCL pts. Clinical trials in MCL should employ the MIPI as a risk-stratification tool, and novel approaches are urgently needed for pts in the high-risk group. Disclosures: No relevant conflicts of interest to declare.

Evaluation of the Mantle Cell Lymphoma International Prognostic Index (MIPI) as An Indicator of Overall Survival, Progression Free Survival, Survival From Relapse

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5082-5082
Author(s):  
Bijal D. Shah ◽  
Jennifer L. Cultrera ◽  
Lubomir Sokol ◽  
Paul A. Chervenick ◽  
Celeste M. Bello ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Cancer Center ◽  
Entire Cohort ◽  
Social Security Death Index ◽  
Mantle Cell ◽  
Survival After Relapse

Abstract Abstract 5082 Background: Prognosis for survival in mantle cell lymphoma (MCL) has recently been characterized using the MIPI algorithm. Using a retrospectively generated dataset of 150 patients with MCL seen at the H Lee Moffitt Cancer Center we sought to validate this approach in a more heterogeneous population. Methods: Patients were identified by physician survey, and through the use of our pathology and Total Cancer Care databases. Retrospective analysis was conducted with approval of our Institutional Review Board. In total 150 patients with MCL were identified, among whom MIPI data was available for 85 patients with a median followup of 36.8 months. Survival (expressed in months) was verified using our institutional records and the Social Security Death Index. Exploratory analysis of progression (n=79) and survival from the time of relapse (n=43) as stratified by MIPI were also conducted among evaluable patients. Data were compared using Kaplan-Meier survival analyses. Results: Median age was 65y (range 31–87), 73% male, 3% ECOG >1, 88% stage III/IV disease, 36% with extranodal involvement, and 38% with splenomegaly. Evaluation of the entire cohort shows median OS 57 (95% CI: 48, 70.9), median PFS 21.8 (95% CI: 14.2, 25.6), and median survival after relapse 27.6 (95% CI 25.4, 30.8). No benefit in OS was observed among patients receiving Cytarabine (HR 1.04, p=0.91) and/or Rituximab (HR 1.31, p=0.61) with initial chemotherapy. Relationship between PFS and survival after relapse demonstrated rho=0.51 (p<.0001). Among 85 evaluable patients 36% had elevated LDH, while 36% were MIPI-Low, 38% MIPI-Int, and 28% MIPI-High. Stratification by MIPI shows median OS of 30.4 (12.4, 42) for MIPI-High, 64.8 (53,-) for MIPI-Int, and has not been reached by MIPI-Low, with little separation between MIPI-Low and MIPI-Int groups before 60 months. PFS was 6.3 (3.7,15) for MIPI-High, 25.6 (16.5,31) for MIPI Int, and 26.5 (14,40.3) for MIPI-Low, with little separation between MIPI-Low and MIPI-Int groups before 30 months. Survival after relapse was 12.4 (9.1,25.4) for MIPI-High, 34.2 (27.6,-) for MIPI-Int, and was not reached for MIPI-Low, again with little separation between MIPI-Low and MIPI-Int groups before 30 months. Conclusions: In our experience, the MIPI remains an effective tool for stratification of OS in MCL, however, extended followup is needed to realize such differences among those with MIPI-Low and MIPI-Int disease. The MIPI was similarly effective in predicting a poor PFS and survival from relapse among those with high risk disease, though was of less utility among MIPI-Low and MIPI-Int patients. Disclosures: No relevant conflicts of interest to declare.

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