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Pomalidomide: the new immunomodulatory agent for the treatment of multiple myeloma.

ABSTRACT: In this report, we provide a comprehensive review on the preclinical and clinical investigations conducted in development of the next-generation immunomodulatory drug (IMiD) pomalidomide for the treatment of relapsed/refractory multiple myeloma (MM). We consulted PubMed, MEDLINE, ASH, ASCO annual symposium abstracts and http://clinicaltrials.gov/ for the purpose of this literature review. Twenty-six preclinical and 11 clinical studies were examined. These studies delineate the mechanisms of action of pomalidomide and attest to the robust clinical activity in relapsed/refractory MM. MM is the second most common hematological malignancy in the US. Despite availability of several therapeutic agents, MM remains incurable. Thus, the development of new therapies remains a priority. Pomalidomide is the newest member of the IMiDs class of drugs, and in preclinical and clinical investigations, it has demonstrated an improved efficacy and toxicity profile in comparison to its sister compounds, lenalidomide and thalidomide. Importantly, recent clinical studies have demonstrated its activity in relapsed or refractory myeloma, particularly in lenalidomide and bortezomib-refractory patients. Thus, the addition of pomalidomide to the anti-myeloma armamentarium is widely anticipated to have a significant impact on the overall clinical outcome of advanced stage relapsed and refractory MM patients.

SUBMITTER: Chanan-Khan AA

PROVIDER: S-EPMC3789204 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Pomalidomide: the new immunomodulatory agent for the treatment of multiple myeloma.

Chanan-Khan A A AA Swaika A A Paulus A A Kumar S K SK Mikhael J R JR Rajkumar S V SV Dispenzieri A A Lacy M Q MQ

Blood cancer journal 20130906

In this report, we provide a comprehensive review on the preclinical and clinical investigations conducted in development of the next-generation immunomodulatory drug (IMiD) pomalidomide for the treatment of relapsed/refractory multiple myeloma (MM). We consulted PubMed, MEDLINE, ASH, ASCO annual symposium abstracts and http://clinicaltrials.gov/ for the purpose of this literature review. Twenty-six preclinical and 11 clinical studies were examined. These studies delineate the mechanisms of acti ...[more]

PMID: 24013664

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Project description:Carfilzomib, a selective proteasome inhibitor (PI), is approved for the treatment of patients with relapsed or refractory multiple myeloma (MM). Combination regimens incorporating a PI and immunomodulatory drug (IMiD) have been associated with deep responses and extended survival in patients with newly diagnosed MM (NDMM). Carfilzomib-based combinations with immunomodulators are being extensively studied in the frontline setting. The objective of this review was to describe efficacy and safety data for carfilzomib-based, PI/immunomodulatory combinations in NDMM. Information sources were articles indexed in PubMed and abstracts from key hematology/oncology congresses published between January 2012 and December 2018. PubMed and congresses were searched for prospective clinical studies assessing the combination of carfilzomib with an IMiD for NDMM treatment. Retrospective and preclinical reports, case reports/series, reviews, and clinical studies not evaluating carfilzomib-immunomodulator combinations in NDMM were excluded based on review of titles and abstracts. A total of nine articles and 72 abstracts were deemed relevant and included in the review. A total of six distinct carfilzomib-based, PI/immunomodulator combination regimens have been evaluated in 12 clinical trials. Overall, treatment with these regimens has resulted in deep responses, including high rates of negativity for minimal residual disease. These deep responses have translated to long progression-free survival and overall survival rates. Efficacy results for these regimens have generally been consistent across subgroups defined by age, transplant eligibility, and cytogenetic risk. The safety profile of carfilzomib in NDMM is consistent with that observed in the relapsed-refractory MM setting. Clinical studies have found that carfilzomib-based combinations with immunomodulators are highly active with a favorable safety profile in NDMM. The carfilzomib, lenalidomide, and dexamethasone (KRd) drug backbone is a promising foundation for treatment strategies aimed at achieving long-term, deep responses (functional cures) in the frontline setting. Several ongoing studies are evaluating KRd, with or without anti-CD38 monoclonal antibodies.

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Pomalidomide: the new immunomodulatory agent for the treatment of multiple myeloma.

Publications

Pomalidomide: the new immunomodulatory agent for the treatment of multiple myeloma.

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