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 ◽  
...  

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.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alessia Castellino ◽  
Aung M. Tun ◽  
Yucai Wang ◽  
Thomas M. Habermann ◽  
Rebecca L. King ◽  
...  

AbstractPrimary gastrointestinal (GI) mantle cell lymphoma (MCL) is rare and the optimal management is unknown. We reviewed 800 newly diagnosed MCL cases and found 22 primary (2.8%) and 79 (9.9%) secondary GI MCL cases. Age, sex, and performance status were similar between primary and secondary cases. Secondary cases had more elevations in lactate dehydrogenase (28% vs 0%, P = 0.03) and a trend for a higher MCL international prognostic index (P = 0.07). Observation or local therapy was more common for primary GI MCL (29% vs 8%, P < 0.01), and autologous stem-cell transplant was more common for secondary GI MCL (35% vs 14%, P < 0.05). The median follow-up was 85 months. Primary and secondary GI MCL had similar 5-year progression-free survival (PFS) (30% vs 28%, P = 0.59) and overall survival (OS) (65% vs 66%, P = 0.83). The extent of GI involvement in primary GI MCL affected treatment selection but not outcome, with a 5-year PFS of 43% vs 14% vs 31% (P = 0.48) and OS of 57% vs 71% vs 69% (P = 0.54) in cases with single lesion vs multiple lesions in 1 organ vs multiple lesions in ≥2 organs. Less aggressive frontline treatment for primary GI MCL is reasonable. It is unknown whether more aggressive treatment can result in improved outcomes.


2020 ◽  
Vol 4 (15) ◽  
pp. 3486-3494
Author(s):  
Diego Villa ◽  
Laurie H. Sehn ◽  
Kerry J. Savage ◽  
Cynthia L. Toze ◽  
Kevin Song ◽  
...  

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 &gt;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.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1910-1910
Author(s):  
Michael B. Moller ◽  
Niels T. Pedersen ◽  
Bjarne E. Christensen

Abstract Background: The International Prognostic Index (IPI) is the most commonly used prognostic model in mantle cell lymphoma. However, the prognostic value of IPI is limited. The recently published Follicular Lymphoma International Prognostic Index (FLIPI) is built on variables (age, stage, lactic dehydrogenase, anemia, and nodal disease) which also are pertinent to mantle cell lymphoma. This study was conducted to evaluate the prognostic value of FLIPI in patients with mantle cell lymphoma. Patients and Methods: A population-based series of 93 patients with mantle cell lymphoma diagnosed in a 7-year period were studied. End points of the study were response to therapy, overall survival, and failure-free survival according to IPI and FLIPI. Results: Applied to the whole series, FLIPI identified 3 risk groups with markedly different outcome with 5-year overall survival rates of 65%, 42%, and 8%, respectively (P < .0001; log-rank 28.13; figure below). Notably, the high-risk group comprised 53% of patients. In contrast, IPI only allocated 16% of cases to the high-risk group and had a lower overall predictive capacity (log-rank 24.8). When both FLIPI and IPI were included in a multivariate analysis, only FLIPI was related to survival. In patients treated with CHOP-based regimens (n = 45) FLIPI also had superior predictive capacity compared to IPI (log-rank, 18.51 versus 11.37), and again only FLIPI retained significance in multivariate analysis. Multivariate analysis of failure-free survival also identified FLIPI, and not IPI, as independently significant. Conclusion: FLIPI is the superior prognostic model as compared to IPI and should be the preferred clinical prognostic index in mantle cell lymphoma. Overall survival according to FLIPI risk groups Overall survival according to FLIPI risk groups


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1143-1143 ◽  
Author(s):  
Lihua Pan ◽  
Katherine A Guthrie ◽  
Brian G. Till ◽  
Oliver W. Press ◽  
John M. Pagel ◽  
...  

Abstract Mantle Cell Lymphoma (MCL) exhibits short remission durations and a poor prognosis. To improve on these outcomes, many have advocated the use of high-dose therapy (HDT) and ASCT. The MIPI predicts overall survival (OS) from diagnosis, yet it remains unknown if the MIPI assessed at diagnosis (MIPI-Dx) or prior to transplant (MIPI-Tx) can be used to predict OS from ASCT. To address this question we retrospectively evaluated the association of the MIPI-Dx and MIPI-Tx, and other characteristics with OS following HDT and ASCT in 87 consecutive MCL patients transplanted at our center. Baseline characteristics included: median age at diagnosis=56 years (range, 35–70), median age at transplant=57 years (range, 35 – 70), stage III-IV=97%, median LDH/upper limit of normal (ULN) at diagnosis=0.91 (range, 0.46–5.65), median LDH/ULN at transplant= 0.88 (range, 0.39–3.00), median white blood cell (WBC) count at diagnosis=7.50 x 109 / liter (range, 1.40 – 54.70), mean WBC count at transplant=4.66 x 109 /liter (range, 0.07 – 17.60), median number of prior chemotherapy regimens=2 (range, 1–5). The estimated 5-year OS and PFS for the entire cohort were 56% (95% CI, 39–73%) and 45% (95% CI, 30 – 60%), respectively with a median follow up among surviving patients of 2.0 years (range 0.1 – 10.1 years). The MIPI-Dx was a better predictor of OS (p&lt;0.001) than MIPI-Tx (p=0.09), when evaluated as a continuous variable. Similarly, when stratified as a categorical variable, the MIPI-Dx (p=0.09) was superior to the MIPI-Tx (p=0.34) in estimating survival. When compared to patients with a MIPI-Dx of 0–2, those with a score of 3, 4, and 5–8 at diagnosis had a 3.3 (95% CI 0.3–32, p=0.3), 6.1 (95% CI 0.7–54.8, p=0.11), and 11.1 (95% CI 1.3–92.9, p=0.03) fold higher risk of mortality after transplant, respectively (Figure). We next determined if any pre-transplant factors could improve our ability to predict outcome after ASCT. Multivariable modeling identified pretransplant factors of ECOG PS &gt;0 (hazard ratio (HR) of 3.0, p=0.03), number of prior regimens &gt;2 (HR 5.2, p=0.01), lack of complete remission (CR) (HR 3.4, p=0.04), and elevated LDH (HR 4.4, p=0.01) as associated with higher risk of death after transplant. These results indicate that the MIPI-Dx is a robust prognostic tool that can even be used to predict outcomes after a later transplant, suggesting that it may continue to reflect the biology of an individual patient’s disease over time. Further assessment of survival predictions after ASCT can be made independently by examining pre-transplant factors including performance status, number of prior regimens, attainment of CR, and LDH. Though these data require prospective validation, our results can be used to counsel patients about outcomes and account for potential differences in results from clinical trials of HDT and ASCT for MCL. Figure Figure


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3745-3745 ◽  
Author(s):  
David Salek ◽  
Ingrid Vasova ◽  
Robert Pytlik ◽  
David Belada ◽  
Tomas Papajik ◽  
...  

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


Blood ◽  
2010 ◽  
Vol 115 (8) ◽  
pp. 1530-1533 ◽  
Author(s):  
Christian H. Geisler ◽  
Arne Kolstad ◽  
Anna Laurell ◽  
Riikka Räty ◽  
Mats Jerkeman ◽  
...  

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.


Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 30-40 ◽  
Author(s):  
Jia Ruan

Abstract Mantle cell lymphoma (MCL) is a distinct subtype of B-cell non-Hodgkin lymphoma characterized by the t(11;14)(q13;q32) translocation leading to cyclin D1 overexpression and cell cycle dysregulation. Molecular profiling with gene expression and deep sequencing analyses has identified genomic and epigenomic alterations in pathways regulating the cell cycle, DNA damage response, proliferation, and survival, which contribute to disease progression with important prognostic and therapeutic implications. Clinically, the nonnodal MCL subset is notable for leukemic presentation, indolent behavior, and association with hypermutated IGHV and lack of SOX11 expression, which differentiates it from the conventional nodal MCL. In addition to the Mantle Cell Lymphoma International Prognostic Index score and proliferative gene signatures, 17p/TP53 and 9p/CDKN2A alterations, and genomic complexity have emerged as clinically useful biomarkers of high-risk disease associated with aggressive disease behavior, resistance to chemotherapy, and poor overall survival. Although intensive chemoimmunotherapy regimens that incorporate high-dose cytarabine and stem cell transplantation have improved survival in young and fit MCL patients, the introduction of Bruton tyrosine kinase inhibitors and other novel agents has made effective outpatient-based treatment accessible to nearly all MCL patients. Optimizing combinations of novel agents in the relapsed setting and moving novel agents to the first-line setting have the potential to fundamentally change the MCL therapeutic landscape for the better, especially for patients ineligible for chemotherapy or those with high-risk mutations that are resistant to chemotherapy.


2014 ◽  
Vol 32 (13) ◽  
pp. 1338-1346 ◽  
Author(s):  
Eva Hoster ◽  
Wolfram Klapper ◽  
Olivier Hermine ◽  
Hanneke C. Kluin-Nelemans ◽  
Jan Walewski ◽  
...  

PurposeMantle-cell lymphoma (MCL) is a distinct B-cell lymphoma associated with poor outcome. In 2008, the MCL International Prognostic Index (MIPI) was developed as the first prognostic stratification tool specifically directed to patients with MCL. External validation was planned to be performed on the cohort of the two recently completed randomized trials of the European MCL Network.Patients and MethodsData of 958 patients with MCL (median age, 65 years; range, 32 to 87 years) treated upfront in the trials MCL Younger or MCL Elderly were pooled to assess the prognostic value of MIPI with respect to overall survival (OS) and time to treatment failure (TTF).ResultsFive-year OS rates in MIPI low, intermediate, and high-risk groups were 83%, 63%, and 34%, respectively. The hazard ratios for OS of intermediate versus low and high versus intermediate risk patients were 2.1 (95% CI, 1.5 to 2.9) and 2.6 (2.0 to 3.3), respectively. MIPI was similarly prognostic for TTF. All four clinical baseline characteristics constituting the MIPI, age, performance status, lactate dehydrogenase level, and WBC count, were confirmed as independent prognostic factors for OS and TTF. The validity of MIPI was independent of trial cohort and treatment strategy.ConclusionMIPI was prospectively validated in a large MCL patient cohort homogenously treated according to recognized standards. As reflected in current guidelines, MIPI represents a generally applicable prognostic tool to be used in research as well as in clinical routine, and it can help to develop risk-adapted treatment strategies to further improve clinical outcome in MCL.


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