Epidemiology of Mantle Cell Lymphoma: A Population-Based Study in France

Abstract Abstract 5222 Introduction: Mantle cell lymphoma (MCL) is an aggressive and rare B-cell lymphoma entity representing around 5–8% of non-Hodgkin's lymphomas in adults. To our knowledge no data is available on the epidemiology of MCL in France. We aimed to describe incidence, survival and main clinical characteristics of MCL in a French population. Methods: Patients diagnosed with MCL were identified in three administrative areas covered by an haematological malignancies registry: the Côte d'Or (from 1988 to 2008), the Basse-Normandie (from 1997 to 2006) and the Gironde (from 2002 to 2006). Main clinical features and management characteristics were collected. World age-standardised incidence rates, observed survival and relative survival were estimated for the period 2002–2006. Results: Mantle cell lymphoma was diagnosed in 213 patients over the whole period. Seventy percent of patients were males. Over the period 2002–2006, the age-standardised incidence rate of MCL (per 100,000) was 0.72 in men (n=100) and 0.17 in women (n=35). The median age at diagnosis was 72 years (range: 30–92). Late-stage (III-IV) MCL was diagnosed in 81.5% of patients. MCL international prognostic index (MIPI) was lower or equal to intermediate risk in 36% of patients. The median relative survival time was 41 months (95% confidence interval: 38–62) and was significantly higher in patients with a low or intermediate MIPI (74 months, CI95%: 53–91) than in patients with a high risk (38 months, CI95%: 30–49). Treatment included frontline chemotherapy in 85% patients and 54% patients received rituximab. Ten percent of patients participated in a clinical trial. Conclusion: Epidemiological characteristics of MCL in France were quite similar to epidemiological data reported in other industrialized countries. Incidence rates were characterized by a male-to-female ratio of 4:1. Median overall survival was less than 4 years. Disclosures: No relevant conflicts of interest to declare.

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Ibrutinib-associated tumor lysis syndrome in a patient with mantle cell lymphoma: A case report

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155216637218 ◽

2016 ◽

Vol 23 (3) ◽

pp. 235-239 ◽

Cited By ~ 3

Author(s):

Varinder Kaur ◽

Arjun Swami

Keyword(s):

Mantle Cell Lymphoma ◽

Kinase Inhibitor ◽

Cell Lymphoma ◽

Rare Complication ◽

Tumor Lysis Syndrome ◽

B Cell Lymphoma ◽

Tumor Lysis ◽

Mantle Cell ◽

Hodgkin's Lymphomas

Mantle cell lymphoma accounts for 5–7% of all non-Hodgkin’s lymphomas. Under the current WHO classification, it is categorized as an indolent B cell lymphoma, but has an aggressive clinical course. New insights into leukemogenic molecular pathways of mantle cell lymphoma have uncovered unique therapeutic targets. Ibrutinib, a Bruton’s tyrosine kinase inhibitor, is the newest drug in the arsenal that has shown promising efficacy in relapsed mantle cell lymphoma. Long-term studies have shown that grade 3 or 4 adverse events are infrequent. Asymptomatic lymphocytosis is frequently seen with ibrutinib use in mantle cell lymphoma; however, tumor lysis syndrome is an extremely rare complication. To date, only two patients with ibrutinib-associated tumor lysis syndrome in mantle cell lymphoma have been described in a long-term follow-up study. Both patients met laboratory criteria for tumor lysis syndrome, however, but did not develop clinical tumor lysis syndrome. We, here describe a patient with relapsed mantle cell lymphoma who developed clinical tumor lysis syndrome with ibrutinib monotherapy.

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Diffuse Aggressive Lymphoma

Hematology ◽

10.1182/asheducation-2004.1.221 ◽

2004 ◽

Vol 2004 (1) ◽

pp. 221-236 ◽

Cited By ~ 53

Author(s):

Richard I. Fisher ◽

Thomas P. Miller ◽

Owen A. O'Connor

Keyword(s):

B Cell ◽

Mantle Cell Lymphoma ◽

Phase Ii ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Standard Of Care ◽

Large B Cell Lymphoma ◽

Mantle Cell ◽

Hodgkin's Lymphomas ◽

Large B Cell

Abstract The aggressive non-Hodgkin’s lymphomas can be cured in more than half of the cases. However, there has been great variation in the results reported from individual clinical Phase II trials. This variation in result can be attributed to unrecognized heterogeneity in this group of diseases. Recent clinical and molecular studies have enabled us to define more homogenous population in which new therapies can be studied. For patients with advanced stages of diffuse large B cell lymphoma, a new standard of therapy exists. For patients with localized aggressive non-Hodgkin’s lymphomas, heterogeneity in patient selection prevents us from defining a new standard of care. Finally, in mantle cell lymphoma, new opportunities in drug discovery may permit advances in the treatment of this uniformly fatal malignancy. In Section I, Dr. Richard Fisher reviews the development of combination chemotherapy for patients with advanced stage diffuse large B cell lymphoma. Because of great heterogeneity in patients enrolled in Phase II studies, large randomized Phase III studies were required in the 1980s to define CHOP has the standard of care. This heterogeneity has now been defined carefully in the international prognostic factor index and more recently by gene array studies. It will now need to be incorporated prospectively into studies or retrospectively analyzed to understand clinical trial results. The addition of rituximab to CHOP has now been demonstrated to improve survival in two large Phase III studies in elderly patients. A recently presented study in younger patients suggests a similar benefit. Thus CHOP/rituximab has become the established standard of care for all patients with advanced stage diffuse large B cell lymphoma. Other concepts being evaluated to further improve on these results include: dose intensification; initial treatment with chemotherapy plus allogeneic stem cell transplantation; and infusional chemotherapy. Finally, the status of the treatment for relapsed patients will be defined. In Section II, Dr. Thomas Miller defines the treatment for limited stage aggressive non-Hodgkin’s lymphoma. Randomized trials have demonstrated the critical importance of initial chemotherapy for treatment of these patients. The amount of chemotherapy given needs to be increased for patients with bulky tumors. In most circumstances radiotherapy after the completion of chemotherapy has been shown to be advantageous. A modification of the international prognostic factor index for patients with early stage disease is presented to permit comparisons among different populations. Recently reported early-stage studies need to be analyzed in terms of the heterogeneity of the patients involved to understand the reported results. The addition of monoclonal antibodies, as well as radioimmunotherapy, are being tested in an effort to improve on the results for the poor prognosis patients. In Section III, Dr. Owen O’Connor describes the pathology immunophenotype and natural history of mantle cell lymphoma. Conventional treatment strategies with combination chemotherapy achieved objective responses in approximately half of the patients but no significant impact on survival. The addition to rituximab to CHOP chemotherapy or other treatment strategies appears to improve the remission rate; however, no major changes in survival have also been reported. Excellent single institution results have been reported with HyperCVAD plus rituximab regimen, which is currently being tested in a national cooperative group trial. The most excitement in this field currently relates to the variety of new agents which appear to have significant activity in relapsed patients with mantle cell lymphoma. This includes the proteosome inhibitor, bortezomib, which is shown to have approximately a 50% response rate with some CRs and reasonable durability in early single institution Phase II studies. Larger national multi-center trials are ongoing. In addition, agents such as thalidomide, flavopiridol, and piroxantrone will be reviewed.

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Bortezomib Plus CHOP-Rituximab for Previously Untreated Diffuse Large B-Cell Lymphoma and Mantle Cell Lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2010.31.1142 ◽

2011 ◽

Vol 29 (6) ◽

pp. 690-697 ◽

Cited By ~ 227

Author(s):

Jia Ruan ◽

Peter Martin ◽

Richard R. Furman ◽

Shing M. Lee ◽

Ken Cheung ◽

...

Keyword(s):

B Cell ◽

Mantle Cell Lymphoma ◽

Cell Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Mantle Cell ◽

Grade 3 ◽

Large B Cell

PurposeThe proteasome inhibitor bortezomib may enhance activity of chemoimmunotherapy in lymphoma. We evaluated dose-escalated bortezomib plus standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus rituximab (R) in patients with diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL).Patients and MethodsSeventy-six subjects with untreated DLBCL (n = 40) and MCL (n = 36) received standard CHOP every 21 days (CHOP-21) with R plus bortezomib at 0.7 mg/m2(n = 4), 1.0 mg/m2(n = 9), or 1.3 mg/m2(n = 63) on days 1 and 4 for six cycles.ResultsMedian age was 63 years (range, 20 to 87), and International Prognostic Index (IPI) scores were generally unfavorable (39% with IPI of 2, and 49% with IPI of 3 to 5), as were Mantle Cell Lymphoma International Prognostic Index scores in patients with MCL (28% intermediate risk and 39% high risk). Toxicity was manageable, including neuropathy in 49 subjects (8% grade 2 and 4% grade 3) and grade 3/4 anemia (13%), neutropenia (41%), and thrombocytopenia (25%). For DLBCL, the evaluable overall response rate (ORR) was 100% with 86% complete response (CR)/CR unconfirmed (CRu; n = 35). Intent-to-treat (ITT, n = 40) ORR was 88% with 75% CR/CRu, 2-year progression-free survival (PFS) of 64% (95% CI, 47% to 77%) and 2-year overall survival (OS) of 70% (95% CI, 53% to 82%). For MCL, the evaluable ORR was 91% with 72% CR/CRu (n = 32). The ITT (n = 36) ORR was 81% with 64% CR/CRu, 2-year PFS 44% (95% CI, 27% to 60%) and 2-year OS 86% (95% CI, 70% to 94%). IPI and MIPI correlated with survival in DLBCL and MCL, respectively. Unlike in DLBCL treated with R-CHOP alone, nongerminal center B cell (non-GCB) and GCB subtypes had similar outcomes.ConclusionBortezomib with R-CHOP-21 can be safely administered and may enhance outcomes, particularly in non-GCB DLBCL, justifying randomized studies.

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PAK4 and NAMPT as Novel Therapeutic Targets in Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, and Mantle Cell Lymphoma

Cancers ◽

10.3390/cancers14010160 ◽

2021 ◽

Vol 14 (1) ◽

pp. 160

Author(s):

Husain Yar Khan ◽

Md. Hafiz Uddin ◽

Suresh Kumar Balasubramanian ◽

Noor Sulaiman ◽

Marium Iqbal ◽

...

Keyword(s):

Cell Proliferation ◽

Follicular Lymphoma ◽

B Cell ◽

Mantle Cell Lymphoma ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Mantle Cell ◽

Hodgkin's Lymphomas ◽

Large B Cell

Diffuse large B-cell lymphoma (DLBCL), grade 3b follicular lymphoma (FL), and mantle cell lymphoma (MCL) are aggressive non-Hodgkin’s lymphomas (NHL). Cure rates are suboptimal and novel treatment strategies are needed to improve outcomes. Here, we show that p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyl transferase (NAMPT) is critical for lymphoma subsistence. Dual targeting of PAK4-NAMPT by the Phase I small molecule KPT-9274 suppressed cell proliferation in DLBCL, FL, and MCL. Growth inhibition was concurrent with apoptosis induction alongside activation of pro-apoptotic proteins and reduced pro-survival markers. We observed NAD suppression, ATP reduction, and consequent cellular metabolic collapse in lymphoma cells due to KPT-9274 treatment. KPT-9274 in combination with standard-of-care chemotherapeutics led to superior inhibition of cell proliferation. In vivo, KPT-9274 could markedly suppress the growth of WSU-DLCL2 (DLBCL), Z-138, and JeKo-1 (MCL) sub-cutaneous xenografts, and a remarkable increase in host life span was shown, with a 50% cure of a systemic WSU-FSCCL (FL) model. Residual tumor analysis confirmed a reduction in total and phosphorylated PAK4 and activation of the pro-apoptotic cascade. This study, using various preclinical experimental models, demonstrates the therapeutic potential of targeting PAK4-NAMPT in DLBCL, FL, and MCL. The orally bioavailable, safe, and efficacious PAK4-NAMPT dual inhibitor KPT-9274 warrants further clinical investigation.

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Confirmation of the Mantle-Cell Lymphoma International Prognostic Index in Randomized Trials of the European Mantle-Cell Lymphoma Network

Journal of Clinical Oncology ◽

10.1200/jco.2013.52.2466 ◽

2014 ◽

Vol 32 (13) ◽

pp. 1338-1346 ◽

Cited By ~ 82

Author(s):

Eva Hoster ◽

Wolfram Klapper ◽

Olivier Hermine ◽

Hanneke C. Kluin-Nelemans ◽

Jan Walewski ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Randomized Trials ◽

Cell Lymphoma ◽

Performance Status ◽

International Prognostic Index ◽

External Validation ◽

Treatment Strategies ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Mantle Cell

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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Clinical characteristics and outcomes of primary versus secondary gastrointestinal mantle cell lymphoma

Blood Cancer Journal ◽

10.1038/s41408-020-00394-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Alessia Castellino ◽

Aung M. Tun ◽

Yucai Wang ◽

Thomas M. Habermann ◽

Rebecca L. King ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Cell Lymphoma ◽

Performance Status ◽

International Prognostic Index ◽

Prognostic Index ◽

Local Therapy ◽

Progression Free Survival ◽

Cell Transplant ◽

Multiple Lesions ◽

Mantle Cell

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.

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Therapeutic Activity of Lenalidomide in Mantle Cell Lymphoma and Indolent Non-Hodgkin’s Lymphomas

Advances in Hematology ◽

10.1155/2012/523842 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Marco Gunnellini ◽

Lorenzo Falchi

Keyword(s):

Mantle Cell Lymphoma ◽

Cell Lymphoma ◽

Single Agent ◽

Response Rates ◽

Prognostic Scores ◽

Cell Transplant ◽

Survival Times ◽

Phase Ii Studies ◽

Mantle Cell ◽

Hodgkin's Lymphomas

Mantle cell lymphoma (MCL) comprises 3–10% of NHL, with survival times ranging from 3 and 5 years. Indolent lymphomas represent approximately 30% of all NHLs with patient survival largely dependent on validated prognostic scores. High response rates are typically achieved in these patients with current first-line chemoimmunotherapy. However, most patients will eventually relapse and become chemorefractory with poor outcome. Alternative chemoimmunotherapy regimens are often used as salvage strategy and stem cell transplant remains an option for selected patients. However, novel approaches are urgently needed for patients no longer responding to conventional chemotherapy. Lenalidomide is an immunomodulatory drug with activity in multiple myeloma, myelodisplastic syndrome and chronic lymphoproliferative disorders. In phase II studies of indolent NHL and MCL lenalidomide has shown activity with encouraging response rates, both as a single agent and in combination with other drugs. Some of these responses may be durable. Optimal dose of lenalidomide has not been defined yet. The role of lenalidomide in the therapeutic armamentarium of patients with indolent NHL or MCL will be discussed in the present paper.

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Case Report: A Rare Case of Lupus Nephritis Associated With Mantle Cell Lymphoma

Frontiers in Medicine ◽

10.3389/fmed.2021.759279 ◽

2021 ◽

Vol 8 ◽

Author(s):

Daorina Bao ◽

Ying Tan ◽

Xiaojuan Yu ◽

Bingjie Wang ◽

Hui Wang ◽

...

Keyword(s):

Renal Function ◽

Lupus Nephritis ◽

Mantle Cell Lymphoma ◽

Lupus Erythematosus ◽

Rare Case ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Lymphoid Cells ◽

Glomerular Injury ◽

Mantle Cell

In this research, we described a very rare case of secondary lupus nephritis associated with B-cell lymphoma. An 84-year-old man was hospitalized at our institute for lower extremity edema persisting for over 2 months. He was diagnosed with systemic lupus erythematosus based on clinical and laboratory criteria, which showed impaired renal function and nephrotic syndrome with predominant hematuria. Renal biopsy showed IV+V lupus nephritis with highly infiltrated lymphoid cells in the kidney. Secondary lupus nephritis was suspected based on the possible pathogenesis of glomerular injury due to mantle cell lymphoma. Low-dose dexamethasone, rituximab, and lenalidomide were immediately started on the patient, and his renal function was improved after the first cycle of chemotherapy.

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