scholarly journals Relapsed Mantle Cell Lymphoma: Current Management, Recent Progress, and Future Directions

2021 ◽  
Vol 10 (6) ◽  
pp. 1207
Author(s):  
David A Bond ◽  
Peter Martin ◽  
Kami J Maddocks
Keyword(s):  
Mantle Cell Lymphoma ◽  
Kinase Inhibitors ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
Single Agent ◽  
Treatment Strategies ◽  
Future Directions ◽  
Car T ◽  
Mantle Cell ◽  
Relapsed Disease

The increasing number of approved therapies for relapsed mantle cell lymphoma (MCL) provides patients effective treatment options, with increasing complexity in prioritization and sequencing of these therapies. Chemo-immunotherapy remains widely used as frontline MCL treatment with multiple targeted therapies available for relapsed disease. The Bruton’s tyrosine kinase inhibitors (BTKi) ibrutinib, acalabrutinib, and zanubrutinib achieve objective responses in the majority of patients as single agent therapy for relapsed MCL, but differ with regard to toxicity profile and dosing schedule. Lenalidomide and bortezomib are likewise approved for relapsed MCL and are active as monotherapy or in combination with other agents. Venetoclax has been used off-label for the treatment of relapsed and refractory MCL, however data are lacking regarding the efficacy of this approach particularly following BTKi treatment. Anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapies have emerged as highly effective therapy for relapsed MCL, with the CAR-T treatment brexucabtagene autoleucel now approved for relapsed MCL. In this review the authors summarize evidence to date for currently approved MCL treatments for relapsed disease including sequencing of therapies, and discuss future directions including combination treatment strategies and new therapies under investigation.

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 Venetoclax as a single agent and in combination with PI3K‐MTOR1/2 kinase inhibitors against ibrutinib sensitive and resistant mantle cell lymphoma

2018 ◽  
Vol 184 (2) ◽  
pp. 298-302 ◽  
Author(s):  
Huijuan Jiang ◽  
Tint Lwin ◽  
Xiaohong Zhao ◽  
Yuan Ren ◽  
Grace Li ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Kinase Inhibitors ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Mantle Cell

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.

New Treatment Options in Mantle Cell Lymphoma

2015 ◽  
Vol 11 (2) ◽  
pp. 134
Author(s):  
Michelle Furtado ◽  
Simon Rule ◽  
◽  
◽  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
B Cell Lymphoma ◽  
Proteasome Inhibition ◽  
Free Treatment ◽  
Mantle Cell ◽  
New Treatment ◽  
The Many ◽  
Relapsed Disease

Mantle cell lymphoma is an incurable disease that generally exhibits a poor prognosis. Recent advances in targeted therapies have increased the available treatment options, in particular for patients with relapsed disease, and offer the prospect for better long-term disease control and potentially chemotherapy-free treatment. Established therapies, such as proteasome inhibition and immunomodulatory agents, are beginning to be recognised as useful in the management of mantle cell lymphoma (MCL) alongside the many emerging classes of drugs (Bruton’s tyrosine kinase [BTK] inhibitors, phosphatidylinositol-4, 5-bisphosphate 3-kinase [PI3k] inhibitors and B cell lymphoma 2 [BCL2] inhibitors) that show promise in this disease. We review the newer agents and drug combinations available for the treatment of MCL.

scholarly journals Cost-effectiveness for KTE-X19 CAR T therapy for adult patients with relapsed/refractory mantle cell lymphoma in the United States

2021 ◽  
Vol 24 (1) ◽  
pp. 421-431
Author(s):  
Claire L. Simons ◽  
Daniel Malone ◽  
Michael Wang ◽  
Gregory A. Maglinte ◽  
Tim Inocencio ◽  
...  
Keyword(s):  
United States ◽  
Cost Effectiveness ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
The United States ◽  
Adult Patients ◽  
Car T ◽  
Mantle Cell

Treatment options for mantle cell lymphoma

2015 ◽  
Vol 16 (16) ◽  
pp. 2497-2507 ◽  
Author(s):  
Piotr Smolewski ◽  
Magdalena Witkowska ◽  
Tadeusz Robak
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
Mantle Cell

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.

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