Lenalidomide-bendamustine-rituximab in patients older than 65 years with untreated mantle cell lymphoma

Albertsson-Lindblad, Alexandra; Kolstad, Arne; Laurell, Anna; Räty, Riikka; Grønbæk, Kirsten; Sundberg, Jan; Pedersen, Lone Bredo; Ralfkiær, Elisabeth; Karjalainen-Lindsberg, Marja Liisa; Sundström, Christer; Ehinger, Mats; Geisler, Christian H.; Jerkeman, Mats

doi:10.1182/blood-2016-03-704023

Cited by 75 publications

(55 citation statements)

References 35 publications

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“…In the Nordic MCL4 study, after 6 cycles of rituximab, bendamustine, and lenalidomide, the percentage of patients among 32 evaluable patients who were MRD positive by qualitative nested PCR was 56% in BM and 61% in PB. 26 In a smaller phase 2 study, clonotypes for MRD assessment were identified by HTS in 19 of 23 patients, and 77% of 13 patients with PB samples were MRD negative by HTS after 3 cycles of R-bendamustine. 27 To the best of our knowledge, there are no currently available data regarding the effects of new targeted treatment drugs such as ibrutinib on MRD in MCL.…”

Section: Mrd During and After Induction Treatmentmentioning

confidence: 99%

Minimal residual disease in mantle cell lymphoma: insights into biology and impact on treatment

Hoster

Pott

2016

Hematology

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Despite the recent substantial improvement of clinical outcome in mantle cell lymphoma (MCL), resistance to immunochemotherapy and common relapses are challenges for long-term tumor control. The assessment of minimal residual disease (MRD) by real-time quantitative polymerase chain reaction has emerged as a widely feasible and standardized tool for direct assessment of therapy-induced reduction of tumor burden and regrowth after cytotoxic treatment in MCL, with much improved sensitivity compared with conventional staging procedures. Several studies have shown that intensification of initial treatment, which has resulted in improved clinical outcome, is immediately reflected in higher molecular remission rates; they have also shown that high-dose consolidation might not be able to compensate for less intensive induction regimens. Persistence or reappearance of MRD in clinical remission proved to be highly predictive for imminent clinical relapse associated with shorter overall survival. Therefore, the investigation of novel MRD-guided treatment strategies aimed at early eradication of MRD and pre-emptive treatment of molecular relapse seems warranted. Furthermore, the integration of MRD assessment into clinical response criteria could result in a more specific and potentially earlier end point for treatment efficacy. New technical developments such as high-throughput sequencing will further enhance the wide applicability of MRD detection in MCL.Learning Objectives

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Section: Mrd During and After Induction Treatmentmentioning

confidence: 99%

Minimal residual disease in mantle cell lymphoma: insights into biology and impact on treatment

Hoster

Pott

2016

Hematology

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“…In a retrospective cohort study of myelodysplastic syndrome (MDS) patients, lenalidomide was not associated with an increased risk of SPM or transformation to AML [194]. Finally, a recent report of lenalidomide with rituximab and bendamustine as first line therapy for elderly mantle cell lymphoma patients showed a higher number of SPMs than expected, with 9 SPMs in 8 patients (16%) including 2 hematologic and 5 solid tumors [195]. …”

Section: Imids and Second Primary Malignanciesmentioning

confidence: 99%

Immunomodulatory Drugs in Multiple Myeloma: Mechanisms of Action and Clinical Experience

Holstein

McCarthy

2017

Drugs

172

174

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Over the last two decades, the outcomes for patients with multiple myeloma, a plasma cell malignancy, have dramatically improved. The development of the immunomodulatory drugs (IMiDs) which include thalidomide, lenalidomide, and pomalidomide, has contributed significantly to these improved outcomes. While thalidomide is now less commonly prescribed, lenalidomide is widely used in the treatment of newly diagnosed transplant-eligible and transplant-ineligible patients, in the maintenance setting post-transplant and in the relapsed/refractory setting, while pomalidomide is currently utilized in the relapsed/refractory setting. The IMiDs have been reported to have a multitude of activities, including anti-angiogenic, cytotoxic, and immunomodulatory, however, the more recent discoveries that the IMiDs bind to cereblon and thus regulate the ubiquitination of key transcription factors including IKZF1 and IKZF3, have provided greater insight into their mechanism of action. Here the clinical efficacy of these agents in myeloma is reviewed as well as discussion of structure-function relationship, the molecular mechanisms of action, and the association of IMiDs with second primary malignancies and thrombosis.

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“…It is a CD20‐specific monoclonal antibody which depletes peripheral blood B cells and can also cause prolonged hypogammaglobuinaemia, predisposing to infections . All reported cases of necrotising retinitis in patients who were on rituximab had complicating factors such as concurrent other intensive immunosuppression and corticosteroid therapy . Most cases were of CMV retinitis, with one case each of ARN and PORN .…”

Section: Biologic Therapy and Viral Retinitismentioning

confidence: 99%

Viral retinitis: diagnosis and management in the era of biologic immunosuppression: A review

Lightman

Tomkins-Netzer

2019

Clinical Exper Ophthalmology

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Necrotising retinitis is a rare ocular infection that historically led to high rates of visual morbidity. While acute retinal necrosis occurs in immunocompetent patients, the majority of cases are associated with immunocompromise such as in cytomegalovirus retinitis and progressive outer retinal necrosis. This review summarises the clinical and diagnostic features, management, and outcomes of herpetic retinitis. Iatrogenic immunosuppression is increasingly being utilised for a wide range of indications, and biologic agents especially so due to their targeted nature. While the intended actions are well‐studied, the flow‐on effects and complex interaction with host immunity are not well understood. Furthermore, biologics are frequently used concomitantly with other immunosuppressive agents, potentiating the immunodepression. This article reviews the literature on biologic immunosuppression and viral retinitis, and presents an approach to the vulnerable or affected patient. Early identification, prompt and aggressive treatment, and a multidisciplinary approach to managing immunodeficiency are the cornerstones of management.

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Lenalidomide-bendamustine-rituximab in patients older than 65 years with untreated mantle cell lymphoma

Abstract: Key Points Addition of lenalidomide to R-B is highly active in patients with untreated MCL, but associated with unexpected high rates of infections and SPMs.

Cited by 75 publications

References 35 publications

Minimal residual disease in mantle cell lymphoma: insights into biology and impact on treatment

Minimal residual disease in mantle cell lymphoma: insights into biology and impact on treatment

Immunomodulatory Drugs in Multiple Myeloma: Mechanisms of Action and Clinical Experience

Viral retinitis: diagnosis and management in the era of biologic immunosuppression: A review

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