Initial therapy of mantle cell lymphoma

Mantle cell lymphoma is a well-recognized distinct clinicopathologic subtype of B-cell non-Hodgkin lymphoma. The current World Health Organization (WHO) classification subdivides this entity into aggressive and other variants. The disease has a predilection for older males, and patients typically present at an advanced stage with frequent splenomegaly and extranodal involvement including bone marrow, peripheral blood, gastrointestinal, and occasional central nervous system involvement. Early studies of therapy outcomes in this disease revealed that while response rates where high, relapse was expected after a limited period of time. Prolonged survival was uncommon, with initial median survival rates typically in the 3–4-year range. Those with a high proliferative rate, blastoid morphology, and selected clinical features were recognized as having a worse prognosis. Therapeutic approaches have diverged into aggressive therapies with high response rates and promising progression free survival rates, which may be applied to younger healthy patients, and less aggressive approaches. Aggressive therapies include intensive chemotherapy alone or chemotherapy followed by autologous stem cell transplant, which has been shown to be most effective when applied in first remission. Whether these more intense therapies result in improved survival as compared with less aggressive therapies is not well established. Allogeneic transplant has also been investigated, although high treatment-related mortality and the risk of chronic graft versus host disease and the relatively advanced age of this patient population have tempered enthusiasm for this approach. A number of less aggressive therapies have been shown to produce promising results. Consolidation and maintenance strategies are an active area of investigation. A number of newer agents have shown promising activity in relapsed disease, and are being investigated in the front-line setting. Overall survival rates are improving in this disease, with current studies suggesting a median survival of 5 or more years.

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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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Rituximab maintenance improves progression-free and overall survival rates after combined immuno-chemotherapy (R-FCM) in patients with relapsed follicular and mantle cell lymphoma: Final results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.7502 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 7502-7502 ◽

Cited By ~ 15

Author(s):

M. Dreyling ◽

R. Forstpointner ◽

M. Gramatzki ◽

H. Böck ◽

M. Hänel ◽

...

Keyword(s):

Overall Survival ◽

Mantle Cell Lymphoma ◽

Cell Lymphoma ◽

Survival Rates ◽

Progression Free Survival ◽

Remission Induction ◽

Low Grade ◽

Free Survival ◽

Mantle Cell ◽

The Impact

7502 Background: Rituximab (R) prolongs the progression-free survival (PFS) in patients with follicular lymphoma (FL) when given either simultaneously with or as maintenance after chemotherapy only. Methods: In the current study the impact of R maintenance after remission induction with an R-containing combined immuno-chemotherapy (R-FCM) was evaluated. Patients with advanced stage relapsed or refractory FL and mantle cell lymphoma (MCL) were eligible. The study design comprized 4 courses of chemotherapy with Fludarabine (25 mg/m2/d days 1–3), Cyclophosphamide (200 mg/m2/d days 1–3) and Mitoxantrone (8 mg/m2/d day 1) (FCM) ± Rituximab (375 mg/m2/d day 0). Patients entering a complete (CR) or partial remission (PR) underwent a second randomization for R maintenance (4 weekly doses (375 mg/m2/d) at three and nine months after end of induction) or observation only. Randomization was stratified for histology, prior therapies (up to 2 lines vs. >2), induction (±R), and response (CR vs. PR). After improved outcome of the R-FCM arm had been observed in the initial 147 randomized patients, all subsequent patients received a combined immuno-chemotherapy induction. Results: 176 of 195 randomized cases are evaluable, 138 of whom had received an R-containing induction. In these patients (as well as the total group) the median PFS after end of induction has not been reached in the R-maintenance arm in contrast to 17 months in patients with no further treatment (p = 0.001). This improvement was seen both in FL (n = 81; p = 0,035) and MCL (n = 47; p = 0,049). More importantly, overall survival rate was also improved after R maintenance with borderline significance (3 y rate 82% vs. 55%; p = 0,056). No major sided effects of R maintenance have been observed and the rate of serious infections was similar in both study arms (p = 0.72). Conclusions: The final analysis of this study confirms that R maintenance after combined immuno-chemotherapy (R-FCM) is highly effective and improves the progression-free survival—with a strong trend towards improved overall survival—of patients with relapsed FL and MCL. [Table: see text]

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Rituximab and CHOP Induction Therapy for Newly Diagnosed Mantle-Cell Lymphoma: Molecular Complete Responses Are Not Predictive of Progression-Free Survival

Journal of Clinical Oncology ◽

10.1200/jco.2002.20.5.1288 ◽

2002 ◽

Vol 20 (5) ◽

pp. 1288-1294 ◽

Cited By ~ 117

Author(s):

Orion M. Howard ◽

John G. Gribben ◽

Donna S. Neuberg ◽

Michael Grossbard ◽

Christina Poor ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Induction Therapy ◽

Cell Lymphoma ◽

Progression Free Survival ◽

Response Rates ◽

Molecular Response ◽

Newly Diagnosed ◽

Chop Chemotherapy ◽

Free Survival ◽

Mantle Cell

PURPOSE: To evaluate the efficacy of rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) induction therapy in patients with newly diagnosed mantle-cell lymphoma (MCL). PATIENTS AND METHODS: From March 1997 to May 1999, 40 previously untreated patients with stage II through IV MCL were treated with six cycles of rituximab and CHOP chemotherapy in a phase II trial. Pretreatment and interval peripheral-blood (PB) and bone marrow (BM) specimens were also analyzed by polymerase chain reaction (PCR) for tumor-specific BCL-1/immunoglobulin H (IgH) translocations and clonal IgH rearrangements. Study end points included clinical and molecular response rates and long-term progression-free survival (PFS). RESULTS: Forty-eight percent of patients achieved a complete response (CR)/CR unconfirmed (CRu), and 48% of patients obtained a partial response (PR). However, 28 of the 40 patients have already relapsed or developed progressive disease with a median PFS of 16.6 months. Twenty-five patients had PCR-detectable BCL-1/IgH or clonal IgH products in PB or BM at diagnosis. Nine of the 25 informative patients had no evidence of PCR-detectable disease in PB or BM after rituximab and CHOP therapy. However, patients who achieved molecular remissions in PB or BM had PFS similar to patients without molecular remissions (16.5 v 18.8 months, P = .51). CONCLUSION: Favorable clinical and molecular response rates associated with rituximab and CHOP chemotherapy do not translate into prolonged PFS in MCL. Nevertheless, rituximab and combination chemotherapy may transiently clear PB or BM of detectable tumor cells, prompting additional consideration of antibody-based in vivo purging in subsequent clinical trials.

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Factors Associated with Progression-Free Survival in Mantle Cell Lymphoma Patients Treated with Autologous Stem Cell Transplant

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2015.11.637 ◽

2016 ◽

Vol 22 (3) ◽

pp. S229-S230

Author(s):

Peter Riedell ◽

Amanda Cashen ◽

Nancy Bartlett ◽

Feng Gao

Keyword(s):

Stem Cell ◽

Mantle Cell Lymphoma ◽

Stem Cell Transplant ◽

Cell Lymphoma ◽

Progression Free Survival ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

Free Survival ◽

Factors Associated ◽

Mantle Cell

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Autologous vs Allogeneic Cell Transplantation for Mantle Cell Lymphoma (MCL): Outcomes over a 10-Year Period at City of Hope.

Blood ◽

10.1182/blood.v104.11.894.894 ◽

2004 ◽

Vol 104 (11) ◽

pp. 894-894 ◽

Cited By ~ 3

Author(s):

Leslie L. Popplewell ◽

A. Nademanee ◽

Nora Carter ◽

Jasmine Zain ◽

Amrita Krishnan ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Advanced Disease ◽

Cell Lymphoma ◽

Progression Free Survival ◽

Disease Status ◽

Autologous Stem Cell Transplant ◽

P Value ◽

Cell Transplant ◽

Mantle Cell ◽

Unknown Status

Abstract Mantle cell lymphoma (MCL) carries a poor prognosis with standard therapy. Both allogeneic (ALLO) and autologous stem cell transplant (ASCT) approaches have been used to intensify therapy in an attempt to achieve lasting remissions. 77 patients were transplanted at City of Hope over a 10-year period (1994–2003), including 13 ALLO and 64 ASCT. Demographics: The majority of patients were male (92% ALLO, and 73% ASCT). Median age was significantly younger for the ALLO, 47 years vs. 55 years for ASCT (p=0.003). ALLO patients had received more prior regimens than ASCTs-- avg 3 in ALLO and 1 in ASCT (p-value 0.0031). Median time from diagnosis to transplantation was 1.3 years for ALLO, 0.81 for ASCT. For ALLO patients, 8% were in first complete remission (CR1), 62% in second or subsequent remission, 23% in relapse, and 8% in unknown status. For ASCT patients, 47% were in CR1, 31% in second or subsequent remission, 14% in relapse, 2% in unknown status. Methods: Conditioning regimens for ASCT include FTBI/VP16/CTX (36), BCNU/VP16/CY (14), BEAM (2), Zevalin/BEAM (4), and other (8). One patient received an ASCT transplant, then received a reduced intensity ALLO transplant at the time of second relapse. Conditioning for ALLO included FTBI/CTX (9), Flu/Mel (3), or BU/CY (1), Results: Median follow-up was 57 months for ALLO, and 26 months for ASCT. 3-year Overall Survival (OS), progression free survival (PFS), and relapse rate was 51%, 53%, and 14% , respectively, for ALLO, and 66%, 57%, and 27% for ASCT. Patients transplanted in 1st CR had a significantly higher 3-year OS (85% vs. 52%, p = 0.0153) and PFS (78% vs. 44%, p = 0.027) a trend to a lower RR than patients transplanted in more advanced disease status. Conclusions: MCL patients transplanted in CR1 fared better than those transplanted with more advanced disease status, regardless of transplant approach. While relapse rates were lower in ALLO patients, this did not translate into improvement in OS or PFS, possibly due to a higher transplant related mortality (TRM). Analysis of PFS curves suggests no plateau on the ASCT curve, while late relapses were uncommon in ALLO patients.

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