Current Treatment Approaches for Mantle-Cell Lymphoma

2005 ◽  
Vol 23 (26) ◽  
pp. 6409-6414 ◽  
Author(s):  
Thomas E. Witzig
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Stage Iv ◽  
Current Treatment ◽  
New Agents ◽  
Male Predominance ◽  
Response To Chemotherapy ◽  
Mantle Cell ◽  
Stage Iv Disease

Mantle-cell lymphoma (MCL) is now recognized as a distinct clinicopathologic subtype of B-cell non-Hodgkin's lymphoma. Patients with MCL are typically older adults with a male predominance and usually present with stage IV disease. The cells are characterized as CD20+ CD5+ CD23− with a t(11;14)(q13;q32) and cyclin D1 overexpression on immunohistochemistry. Response to chemotherapy usually results in a tumor response but unmaintained remissions are short and the median survival is 3 to 4 years. The treatment approach to newly diagnosed patients with MCL depends on the patient's eligibility for stem cell transplantation (SCT). Those who are eligible are usually treated with either rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by SCT or rituximab-HyperCVAD (cyclophosphamide, vincristine, doxorubicin, decadron, cytarabine, and methotrexate) followed by observation. The purine nucleoside analogues also have activity as single agents and with rituximab. Unfortunately none of these approaches can definitively cure patients with MCL, and new agents are needed. Recent studies in patients with relapsed MCL have shown substantial antitumor activity of single-agent bortezomib, single-agent temsirolimus, and the combination of thalidomide and rituximab. Studies integrating these novel agents earlier in the disease course or in combination with each other will hopefully produce more durable responses with less toxicity.

Phase II Study of Rituximab and Cladribine (2-CDA) in Newly Diagnosed Mantle Cell Lymphoma (MCL) (N0189).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2746-2746 ◽  
Author(s):  
David James Inwards ◽  
David W. Hillman ◽  
Paul A. Fishkin ◽  
William L. White ◽  
Roscoe F. Morton ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Stage Iv ◽  
Complete Response ◽  
Mantle Cell ◽  
To Receive

Abstract Background: A previous trial of 2-CDA as a single agent for therapy of mantle cell lymphoma demonstrated this agent to be efficacious with an overall response rate of 81% (31% complete responses) (Blood 1999 Nov 15; 94:660a). A phase II study of the addition of rituximab to 2-CDA was conducted by the North Central Cancer Treatment Group based on improved outcomes achieved by the addition of rituximab to other regimens active in MCL. Methods: This one-stage phase II study was designed to determine the complete response (CR) or complete response/unconfirmed (CRu) rate. Central pathology confirmation of cyclin D1 positive mantle cell lymphoma was required. No previous therapy for lymphoma was allowed, with the exception of splenectomy. The schedule was rituximab 375 mg/m2 IV day 1; 2-CDA 5 mg/m2/d IV days 1–5 of a 4-week cycle. After 2 of the first 6 patients developed grade 4 neutropenia, subsequent patients received either pegfilgrastim or filgrastim support. Patients received 2–6 cycles of therapy, depending on response. Patients were required to achieve at least a PR after 2 cycles of therapy to continue on protocol therapy. Results: Patient characteristics of all 29 eligible pts: median age: 70 (range: 41–86); 21 male, 8 female; PS 0 (55.2%), PS 1 (41.4%), PS 2 (3.5%); stage II (6.9%), stage III (3.5%), stage IV (89.7%); prior splenectomy (20.7%). The only grade 4 adverse events occurring more than once were neutropenia (24.1%) and leucopenia (6.9%). One patient died of cerebral ischemia in the setting of pneumonia without neutropenia. Fifteen (51.7%; 95% CI: 32.5–70.6%) pts achieved a CR; only one has relapsed to date (665 days after starting therapy). Four additional pts achieved a PR. Ten pts have progressed with 4 pts progressing early at 17, 45, 46, and 71 days (two of whom have died). Ten pts (34.0%) went on to receive further therapy off study, 5 in less than a PR after 2 cycles, 2 in PR after study therapy, and 1 who went off study for a rash. Fourteen pts (48.3%) have progressed or gone on to receive additional therapy off study. At last contact, 26 (89.7%) were alive (median follow-up 14.3 months; range: 6–34). One year survival rate is 89.3% (95% CI: 78.5–100). Conclusions: Rituximab and cladribine were well tolerated for the treatment of MCL in a group of elderly patients. The response rate may have been underestimated due to the study design, which required at least a PR after 2 cycles to continue therapy. Despite this, 52% achieved a complete remission. Complete remissions attained with this regimen appear to be durable, with a single relapse to date among 15 patients achieving CR.

Results of a Nonrandomized, Open-Label, Phase II Study of Combined Gemcitabine, Mitoxantrone, and Rituximab in Relapsed or Refractory Mantle Cell Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4452-4452
Author(s):  
Lawrence E. Garbo ◽  
Patrick J. Flynn ◽  
Margaret A. MacRae ◽  
Mary A. Rauch ◽  
Yunfei Wang ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
Single Agent ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Open Label ◽  
Mantle Cell ◽  
Grade 3

Abstract Mantle cell lymphoma (MCL) is an aggressive type of B-cell non-Hodgkin’s lymphoma that usually presents as disseminated disease. Prognosis is poor, and responses to chemotherapy are less durable than those achieved in other types of lymphoma. New treatment options are desperately needed. Gemcitabine has shown activity in MCL as a single agent. In addition, the combination of mitoxantrone and rituximab has also been shown to be active in MCL. However, the use of these drugs in combination has not been evaluated in the treatment of MCL. The primary objective of this study was to determine the efficacy of gemcitabine+mitoxantrone+rituximab in relapsed or refractory MCL; secondary objectives were duration of response, survival at 1-year, progression-free survival (PFS), and toxicity, especially myelotoxicity. Sixteen patients were enrolled between April 2005 and December 2006, and only 15 were evaluable due to one patient’s withdrawal of consent. Patients received gemcitabine 900 mg/m2 IV (30–60 min infusion), mitoxantrone 10 mg/m2 IV (5–10 min infusion), and rituximab 375 mg/m2 IV on Day 1 (max 400 mg/hr). Patients also received gemcitabine 900 mg/m2 on Day 8 of the 21-day cycle. Medication was administered in the following order: gemcitabine→mitoxantrone→rituximab. Patients were to be treated for a maximum of 8 cycles or until the patient had evidence of a response, progressive disease, or intolerable toxicity. The median patient age was 74 years, 100% were white, and 69% were male. Of all patients, 86% had Stage IV MCL at baseline. Patients received a median of 6 cycles (range, 3 – 8). Efficacy results for the evaluable population are CR 13%, PR 27%, PD 13%, and SD 47%. Median PFS was 8.72 months (range, 1.84 – 23.49); median overall survival was 10.03 months (range, 2.50 – 23.49). Grade 3–4 treatment related toxicities reported in >1 patient were neutropenia (93%), leukopenia or thrombocytopenia (53% each), anemia (20%), and asthenia (13%). 60% of patients are currently alive as of July 2007; 9 patients discontinued study treatment due to disease progression (13%), toxicity (27%), MD request (7%), or withdrawal of consent (13%). 7 patients had normal study completion (44%). The study was closed early due to slow accrual owing to alternative treatment which became available at the time. The combination of gemcitabine, mitoxantrone, and rituximab in MCL was well-tolerated with manageable adverse events in spite of 93% neutropenia. Supplemented growth factor use was able to minimize neutropenia. No Grade 3–4 infection was reported. This regimen holds promise in patients with MCL and further studies are warranted. Updated data will be presented.

Bortezomib + DA-EPOCH-R Induction Therapy Followed by Maintenance Bortezomib Versus Observation in Newly Diagnosed Mantle Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3672-3672 ◽  
Author(s):  
Kieron Dunleavy ◽  
Cliona Grant ◽  
Julieanne Hessler ◽  
Barry W. Miller ◽  
Seth M. Steinberg ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Stage Iv ◽  
Patient Characteristics ◽  
Newly Diagnosed ◽  
Mantle Cell ◽  
Before And After ◽  
Stage Iv Disease ◽  
Grade 3

Abstract Abstract 3672 Background: Bortezomib, a proteasome inhibitor, is effective in relapsed/refractory mantle cell lymphoma (MCL) and achieves responses in up to 50% of patients. While its mechanisms of action are broad, in MCL, brotezomib causes cell cycle arrest and induces apoptosis through oxidative/ER stress-mediated up-regulation of noxa. DA-EPOCH-R is an effective platform in MCL. We set out to assess the efficacy of bortezomib in combination with DA-EPOCH-R in newly diagnosed MCL and to assess the efficacy of maintenance bortezomib following induction. Methods: Treatment was divided into three parts: Part A - bortezomib (1.3 or 1.5 mg/m2) on days 1, 4, 8 and 11 for one cycle; Part B - bortezomib (1.3mg/m2) on days 1 and 4 of DA-EPOCH-R (as previously described) for 6 cycles; Part C patients in CR or PR after Part B and without significant neurotoxicity were randomized to maintenance bortezomib (1.3 mg/m2 d 1, 4, 8 and 11 q 8 wks for 18 mos) or observation. Results: Patient characteristics (n=43): median (range) age 58 (41–75); 45% were aged 60y or over; male sex 32 (73%); stage IV disease 100%. At 48 months (with 57 months median potential follow-up), PFS is 50% and OS is 80%. Twenty-four patients randomized to maintenance bortezomib (13) or observation (11) had a similar PFS (p=0.41) (see attached curve). Overall, 50% of patients had at least grade 2 neurotoxicity. At the recommended 1.3mg/m2 dose of bortezomib, 33% of patients required a dose reduction or discontinuation of drug. Other significant toxicities were neutropenic fever/infection in 8% of cycles and grade 3 or 4 thrombocytopenia in 34% of cycles. Conclusions: Bortezomib in combination with DA-EPOCH-R is an effective strategy in patients of all ages with MCL. Maintenance bortezomib (versus observation) does not improve the PFS. However, compared to our historical patients treated with DA-EPOCH-R alone, patients who received DA-EPOCH-R and bortezomib have a significantly better PFS at 48 months (50% versus 19%, respectively). These preliminary results suggest that bortezomib with immunochemothearpy may improve PFS. Accrual continues and responses will be correlated with translational end-points on biopsied tissue sampled before and after bortezomibalone (Part A). Disclosures: No relevant conflicts of interest to declare.

Phase II study of rituximab and cladribine (2-CDA) in newly diagnosed mantle cell lymphoma (MCL) (N0189)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17505-17505
Author(s):  
D. J. Inwards ◽  
D. W. Hillman ◽  
P. A. Fishkin ◽  
W. L. White ◽  
R. F. Morton ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Stage Iv ◽  
Patient Characteristics ◽  
Complete Response ◽  
Mantle Cell

17505 Background: A previous trial of 2-CDA as a single agent for therapy of mantle cell lymphoma demonstrated this agent to be efficacious with an overall response rate of 81% (31% complete responses) (Blood 1999 Nov 15; 94:660a). A phase II study of the addition of rituximab to 2-CDA was conducted by the North Central Cancer Treatment Group based on improved outcomes achieved by the addition of rituximab to other regimens active in MCL. Methods: This one-stage phase II study was designed to determine the complete response (CR) or complete response/unconfirmed (CRu) rate. Central pathology confirmation of cyclin D1 positive mantle cell lymphoma was required. No previous therapy for lymphoma was allowed, with the exception of splenectomy. The shedule was rituximab 375 mg/m2 IV day 1; 2-CDA 5 mg/m2/d IV days 1–5 of a 4-week cycle. After 2 of the first 6 patients developed grade 4 neutropenia, subsequent patients received either pegfilgrastim or filgrastim support. Patients received 2–6 cycles of therapy, depending on response. Patients were required to achieve at least a PR after 2 cycles of therapy to continue on protocol therapy. Results: Patient characteristics of all 29 eligible pts: median age: 70 (range: 41–86); 21 male, 8 female; PS 0 (55.2%), PS 1 (41.4%), PS 2 (3.5%); stage II (6.9%), stage III (3.5%), stage IV (89.7%); prior splenectomy (20.7%). The only grade 4 adverse event occurring more than once was neutropenia (20.7%). One patient died of cerebral ischemia in the setting of pneumonia without neutropenia. Response has been determined in 26 pts with 50.0% (95% CI: 30.0–70.0%) achieving a CR, none of whom have relapsed to date. Three patients progressed early at 17, 45, and 46 days, two of whom have died, and a fourth relapsed day 222. 10 pts (34.0%) went on to receive further therapy off study, 5 in less than a PR after 2 cycles, 2 in PR after study therapy, and 1 who went off study for a rash. At last contact, 26 (89.7%) were alive (median follow-up 10.7 months; range: 1–28). Conclusions: Rituximab and cladribine were well tolerated for the treatment of MCL in a group including elderly patients. The response rate may have been underestimated due to the study design, which required at least a PR after 2 cycles to continue therapy. Despite this, 50% achieved a complete remission. [Table: see text]

scholarly journals Relapsed and/or Refractory Mantle cell Lymphoma: What Role for Temsirolimus?

2012 ◽  
Vol 6 ◽  
pp. CMO.S7327 ◽  
Author(s):  
Sebastian Kirschey ◽  
Susanne Wagner ◽  
Georg Hess
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
Single Agent ◽  
Current Treatment ◽  
Treatment Algorithms ◽  
Dismal Prognosis ◽  
Mantle Cell ◽  
Relapsed Disease ◽  
Future Concepts

Mantle Cell Lymphoma (MCL) is associated with a dismal prognosis. Recently, along with the improved understanding of the pathophysiology of this disease, new first line regimens have been established and in addition novel treatment options have entered the clinical arena. In consequence, prognosis of the disease has fortunately improved. We here focus on the rationale, current clinical knowledge and future concepts of Temsirolimus, an inhibitor of mTOR, in the treatment of MCL. At this time this drug has been shown to be effective as single agent for relapsed disease and early combination data show promising results. In addition, with a brief outline of other treatment options, we aim to guide at which place in the current treatment algorithms Temsirolimus can be integrated into the treatment of MCL patients.

scholarly journals BET bromodomain inhibitor birabresib in mantle cell lymphoma: in vivo activity and identification of novel combinations to overcome adaptive resistance

ESMO Open ◽  
2018 ◽  
Vol 3 (6) ◽  
pp. e000387 ◽  
Author(s):  
Chiara Tarantelli ◽  
Elena Bernasconi ◽  
Eugenio Gaudio ◽  
Luciano Cascione ◽  
Valentina Restelli ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
Antitumour Activity ◽  
Single Agent ◽  
Treatment Strategies ◽  
Bet Inhibitor ◽  
Mantle Cell

BackgroundThe outcome of patients affected by mantle cell lymphoma (MCL) has improved in recent years, but there is still a need for novel treatment strategies for these patients. Human cancers, including MCL, present recurrent alterations in genes that encode transcription machinery proteins and of proteins involved in regulating chromatin structure, providing the rationale to pharmacologically target epigenetic proteins. The Bromodomain and Extra Terminal domain (BET) family proteins act as transcriptional regulators of key signalling pathways including those sustaining cell viability. Birabresib (MK-8628/OTX015) has shown antitumour activity in different preclinical models and has been the first BET inhibitor to successfully undergo early clinical trials.Materials and methodsThe activity of birabresib as a single agent and in combination, as well as its mechanism of action was studied in MCL cell lines.ResultsBirabresib showed in vitro and in vivo activities, which appeared mediated via downregulation of MYC targets, cell cycle and NFKB pathway genes and were independent of direct downregulation of CCND1. Additionally, the combination of birabresib with other targeted agents (especially pomalidomide, or inhibitors of BTK, mTOR and ATR) was beneficial in MCL cell lines.ConclusionOur data provide the rationale to evaluate birabresib in patients affected by MCL.

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

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
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.

Mantle cell lymphoma: a rare cause for a swollen palate

2020 ◽  
Vol 13 (10) ◽  
pp. e238332
Author(s):  
Ayah Mohamed ◽  
Rachel Cowie ◽  
Dáire Shanahan
Keyword(s):  
Mantle Cell Lymphoma ◽  
Hard Palate ◽  
Cell Lymphoma ◽  
Stage Iv ◽  
Accurate Diagnosis ◽  
The Body ◽  
Oral Medicine ◽  
Medicine Department ◽  
Mantle Cell ◽  
Dental Hospital

We describe the case of a 68-year-old woman who was referred to the Oral Medicine Department in the Bristol Dental Hospital in November 2018 regarding a mass in the hard palate. The patient was previously diagnosed with stage IV mantle cell lymphoma of the upper tarsal conjunctiva in December 2014. Further investigations revealed lymphomatous deposits in other sites throughout the body. This patient underwent six cycles of chemotherapy, followed by consolidation LACE autograph and maintenance rituximab. While mantle cell lymphoma very rarely presents on the hard palate, knowledge of its clinical features and differential diagnoses is imperative in its accurate diagnosis and appropriate management.

scholarly journals Mantle cell lymphoma relapsing at the lymphedematous arm.

2013 ◽  
Vol 5 (1) ◽  
pp. e2013016 ◽  
Author(s):  
Giuseppina Massini ◽  
Stefan Hohaus ◽  
Francesco D'Alo' ◽  
Valentina Bozzoli ◽  
Barbara Vannata ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Negative Impact ◽  
Medical Condition ◽  
Stage Iv ◽  
Chronic Medical Condition ◽  
Interstitial Tissue ◽  
Cancer Treatments ◽  
Mantle Cell ◽  
Long Term Survivors

Lymphedema (LE) is a chronic medical condition characterized by lymphatic fluid retention, resulting in tissue swelling. Cancer treatments involving lymph nodes can damage lymph drainage routes, causing accumulation of lymph fluid in the interstitial tissue of related limbs and body areas and secondary LE.  Basically, the LE has a negative impact on physical and mental quality of life. Moreover, 0.07-0.04% of long term survivors (most patients undergone mastectomy) can develop the Stewart-Treves syndrome,  a rare and aggressive multifocal lymphangiosarcoma arising within the LE region. Here we describe a   45-year-old woman  with a massive LE of the left arm,  as a consequence of previous breast cancer,  who  was diagnosed after 4 years  of stage IV mantle cell lymphoma (MCL) . The patient after obtaining complete remission with chemotherapy and ABMT  relapsed of MCL in lymphedema site.

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