Thalidomide therapy induces response in relapsed mantle cell lymphoma

Damaj, Gandhi; Lefrère, François; Delarue, Richard; Varet, Bruno; Furman, Richard R.; Hermine, Olivier

doi:10.1038/sj.leu.2403058

Cited by 46 publications

(22 citation statements)

References 17 publications

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“…One of the properties that may explain its efficacy in multiple myeloma revolves around its potential to modify the stromal environment in the bone marrow, leading to a perturbation in the signaling pathways responsible for plasma cell survival. Damaj et al 33 published a case report on two patients with very heavily pretreated MCL who achieved major durable partial remissions on thalidomide, which in both cases was maintained for over a year on the maintenance therapy. Recently, Kaufmann et al 34 conducted a Phase II study of rituximab (R; 375 mg/m 2 IV weekly times four weekly doses) given concomitantly with thalidomide (T; 200 mg by mouth daily, with a incremental dose increases to 400 mg on day 15).…”

Section: Thalidomide-based Treatmentsmentioning

confidence: 99%

“…Flavopiridol is a pan cyclin-dependent kinase (cdk) inhibitor that binds directly to the ATP-binding site at nanomolar concentration of most cyclin-dependent kinases. 33 It is a potent inhibitor of the Cyclin D1, D2, D3-cdk4/6 complex, the Cyclin E/cdk2 complex, the Cylin B/cdk1 complex, and the Cyclin A/cdk 1complex. As such, it has been found to be a potent inducer of apoptosis when used with traditional chemotherapy drugs in a schedule dependent manner.…”

Section: Other Promising Agentsmentioning

confidence: 99%

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Diffuse Aggressive Lymphoma

Fisher¹,

Miller²,

O’Connor³

2004

Hematology

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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 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 ong...

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Section: Thalidomide-based Treatmentsmentioning

confidence: 99%

Section: Other Promising Agentsmentioning

confidence: 99%

Diffuse Aggressive Lymphoma

Fisher¹,

Miller²,

O’Connor³

2004

Hematology

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“…The patient received daily single-agent thalidomide by oral ingestion at a dose of 800 mg and achieved a partial remission, which was maintained for 6 months. Additional studies also reported cases of refractory mantle cell lymphoma or recurrent lymphoma successfully treated with thalidomide (15,34,35), achieving an overall response rate of 81%, with a CR rate of 31%, when thalidomide was used in combination with rituximab in 16 relapsed mantle cell lymphoma patients.…”

Section: Discussionmentioning

confidence: 99%

Thalidomide plus chemotherapy exhibit enhanced efficacy in the clinical treatment of T-cell non-Hodgkin’s lymphoma: A prospective study of 46 cases

Wang

Zhao

et al. 2014

Molecular and Clinical Oncology

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“…Thalidomide and lenalidomide have shown modest activity in relapsed disease, suggesting possible enhanced activity in the frontline setting. [30][31][32] Rummel et al 33 reported on the activity of bendamustine combined with rituximab in relapsed lowgrade lymphoma and MCL. Only 16 patients enrolled on that study had MCL histology, but the overall response rate of 75% (CR 50%) in this subset supported studying this agent in randomized trials.…”

Section: New Chemotherapy Agentsmentioning

confidence: 99%

Hematopoietic SCT for mantle cell lymphoma: is it the standard of care?

Nabhan

Ragam

Bitran

et al. 2010

Bone Marrow Transplant

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The role of hematopoietic SCT (HSCT) in mantle cell lymphoma (MCL) remains controversial. Most studies that support the utility of this approach were small phase II single-institution studies with highly selected patient populations. Furthermore, recent evidence suggesting initial observation as opposed to immediate therapy in MCL, coupled with the availability of newer therapeutic agents, complicates the role of HSCT and argues for conducting large phase III studies. In this review, we discuss the limitation of current evidence and the lack of large definitive studies. We then analyze the data on HSCT in relapsed MCL and as a frontline approach propose applying the new prognostic index, MIPI (MCL International Prognostic Index), in the decision making.

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Thalidomide therapy induces response in relapsed mantle cell lymphoma

Cited by 46 publications

References 17 publications

Diffuse Aggressive Lymphoma

Diffuse Aggressive Lymphoma

Thalidomide plus chemotherapy exhibit enhanced efficacy in the clinical treatment of T-cell non-Hodgkin’s lymphoma: A prospective study of 46 cases

Hematopoietic SCT for mantle cell lymphoma: is it the standard of care?

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