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Future Oncology (London, England) Feb 2017
Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Drug Resistance, Neoplasm; Humans; Immunologic Factors; Multiple Myeloma; Retreatment; Thalidomide
PubMed: 28116940
DOI: 10.2217/fon-2016-0559 -
Expert Review of Hematology Dec 2014Once characterized by a very poor outcome, multiple myeloma (MM) now has a significantly prolonged survival, with major improvements allowed by the use of 'novel... (Review)
Review
Once characterized by a very poor outcome, multiple myeloma (MM) now has a significantly prolonged survival, with major improvements allowed by the use of 'novel agents': proteasome inhibitors (first-in-class bortezomib) and immunomodulatory compounds (IMiDs; first-in-class thalidomide and lenalidomide). However, the vast majority - if not all - of patients with MM ultimately end up being refractory to all existing drugs, including these efficient novel agents. There is a clear unmet medical need in this situation, which warrants the development of the next generation of proteasome inhibitors and IMiDs, as well as new drug classes. This drug profile focuses on pomalidomide, the next generation IMiD, recently approved by the US FDA and the EMA for patients with relapsed or refractory MM who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on their last therapy.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Humans; Immunologic Factors; Lenalidomide; Multiple Myeloma; Neoplasm Recurrence, Local; Oligopeptides; Pyrazines; Thalidomide
PubMed: 25265911
DOI: 10.1586/17474086.2014.966074 -
Expert Opinion on Investigational Drugs May 2011The Office of National Statistics (London, UK) has reported 4040 new patients in the year 2007, with an annual age standardized incidence rate of 4.8 per 100,000... (Review)
Review
INTRODUCTION
The Office of National Statistics (London, UK) has reported 4040 new patients in the year 2007, with an annual age standardized incidence rate of 4.8 per 100,000 population (range 4.7 - 5.0). Overall survival (OS) in the last decade has improved from 2 - 3 years to 7 - 8 years in the UK. The introduction of IMids for the treatment of myeloma has had a significant impact on outcomes in this life-threatening disease.
AREAS COVERED
Pomalidomide, a thalidomide analogue, is a promising anti-myeloma agent with encouraging responses in relapsed/refractory myeloma patients. Pomalidomide has a potent anti-myeloma activity in vitro and in vivo, acting both directly on myeloma cells and on the cells in the bone marrow microenvironment. We have reviewed the chemistry and mechanisms of action of pomalidomide and the literature on pre-clinical and early Phase I and II clinical trials that demonstrates significant clinical efficacy in the relapsed setting and in lenalidomide refractory myeloma patients.
EXPERT OPINION
Pomalidomide has shown significant activity in relapsed/refractory disease and is now being taken into Phase III trials in combination with dexamethasone. The exact place of pomalidomide in the management of myeloma, however, is evolving as more clinical experience is gained with this agent and further data published from clinical trials.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Dexamethasone; Humans; Multiple Myeloma; Thalidomide
PubMed: 21413906
DOI: 10.1517/13543784.2011.567265 -
Hematology (Amsterdam, Netherlands) Dec 2022Extramedullary disease (EMD) is characterized by plasma cells outside of bone marrow in multiple myeloma (MM) patients, which results in an adverse prognosis. EMD...
OBJECTIVES
Extramedullary disease (EMD) is characterized by plasma cells outside of bone marrow in multiple myeloma (MM) patients, which results in an adverse prognosis. EMD treatment is yet challenging even in the era of novel drugs. Only limited data are available on pomalidomide-based therapy for EMD patients. The purpose of the current study was to assess the efficacy of pomalidomide-based therapy in EMD.
METHODS
The current retrospective analysis of six patients assessed the utility of pomalidomide-based therapy in the treatment of EMD.
RESULTS
The median age at diagnosis was 55 (47-70) years. A serological response was observed: 16% ( = 1) complete response (CR), 67% ( = 4) partial response (PR), and 16% ( = 1) progressive disease (PD). Extramedullary overall response rate (ORR) was 83% ( = 5), with 50% ( = 3) CR, 33% ( = 2) PR, and extramedullary progression in one patient. The median progression-free survival (PFS) was 5 months and the median overall survival (OS) was 8 months from diagnosis of EMD.
DISCUSSION AND CONCLUSION
Pomalidomide-based therapy showed efficacy in these previously treated patients with EMD.
Topics: Aged; Angiogenesis Inhibitors; Female; Humans; Male; Middle Aged; Multiple Myeloma; Progression-Free Survival; Retrospective Studies; Thalidomide; Treatment Outcome
PubMed: 35068387
DOI: 10.1080/16078454.2021.2019364 -
The Lancet. Haematology Oct 2023Multiple myeloma remains incurable, and heavily pretreated patients with relapsed or refractory disease have few good treatment options. Belantamab mafodotin showed... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of single-agent belantamab mafodotin versus pomalidomide plus low-dose dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-3): a phase 3, open-label, randomised study.
BACKGROUND
Multiple myeloma remains incurable, and heavily pretreated patients with relapsed or refractory disease have few good treatment options. Belantamab mafodotin showed promising results in a phase 2 study of patients with relapsed or refractory multiple myeloma at second or later relapse and a manageable adverse event profile. We aimed to assess the safety and efficacy of belantamab mafodotin in a phase 3 setting.
METHODS
In the DREAMM-3 open-label phase 3 study, conducted at 108 sites across 18 countries, adult patients were enrolled who had confirmed multiple myeloma (International Myeloma Working Group criteria), ECOG performance status of 0-2, had received two or more previous lines of therapy, including two or more consecutive cycles of both lenalidomide and a proteasome inhibitor, and progressed on, or within, 60 days of completion of the previous treatment. Participants were randomly allocated using a central interactive response technology system (2:1) to receive belantamab mafodotin 2·5 mg/kg intravenously every 21 days, or oral pomalidomide 4·0 mg daily (days 1-21) and dexamethasone 40·0 mg (20·0 mg if >75 years) weekly in a 28-day cycle. Randomisation was stratified by previous anti-CD38 therapy, International Staging System stage, and number of previous therapies. The primary endpoint was progression-free survival in all patients who were randomly allocated. The safety population included all randomly allocated patients who received one or more doses of study treatment. This trial is registered with ClinicalTrials.gov, NCT04162210, and is ongoing. Data cutoff for this analysis was Sept 12, 2022.
FINDINGS
Patients were recruited between April 2, 2020, and April 18, 2022. As of September, 2022, 325 patients were randomly allocated (218 to the belantamab mafodotin group and 107 to the pomalidomide-dexamethasone group); 184 (57%) of 325 were male and 141 (43%) of 325 were female, 246 (78%) of 316 were White. Median age was 68 years (IQR 60-74). Median follow-up was 11·5 months (5·5-17·6) for belantamab mafodotin and 10·8 months (5·6-17·1) for pomalidomide-dexamethasone. Median progression-free survival was 11·2 months (95% CI 6·4-14·5) for belantamab mafodotin and 7·0 months (4·6-10·6) for pomalidomide-dexamethasone (hazard ratio 1·03 [0·72-1·47]; p=0·56). Most common grade 3-4 adverse events were thrombocytopenia (49 [23%] of 217) and anaemia (35 [16%]) for belantamab mafodotin, and neutropenia (34 [33%] of 102) and anaemia (18[18%]) for pomalidomide-dexamethasone. Serious adverse events occurred in 94 (43%) of 217 and 40 (39%) of 102 patients, respectively. There were no treatment-related deaths in the belantamab mafodotin group and one (1%) in the pomalidomide-dexamethasone group due to sepsis.
INTERPRETATION
Belantamab mafodotin was not associated with statistically improved progression-free survival compared with standard-of-care, but there were no new safety signals associated with its use. Belantamab mafodotin is being tested in combination regimens for relapsed or refractory multiple myeloma.
FUNDING
GSK (study number 207495).
Topics: Aged; Female; Humans; Male; Anemia; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Multiple Myeloma; Neoplasm Recurrence, Local; Middle Aged
PubMed: 37793771
DOI: 10.1016/S2352-3026(23)00243-0 -
Drugs of Today (Barcelona, Spain : 1998) Sep 2013Multiple myeloma is a malignancy of plasma cells in the bone marrow. Currently, multiple myeloma is not considered curable, but it is treatable with different strategies... (Review)
Review
Multiple myeloma is a malignancy of plasma cells in the bone marrow. Currently, multiple myeloma is not considered curable, but it is treatable with different strategies that can combine chemotherapy with autologous hematopoietic stem cell transplantation. Pomalidomide is an orally active thalidomide analogue that has a pleiotropic mechanism of action involving oncolytic, antiangiogenic, immunomodulatory and anti-inflammatory activities. Pomalidomide is extensively metabolized, mainly by the cytochrome P450 3A4 and 1A2 pathways. The safety and efficacy of pomalidomide combined with dexamethasone has been demonstrated in a phase III trial for the treatment of multiple myeloma patients, relapsed/resistant to bortezomib and lenalidomide. Adverse events that were mainly related to myelosuppression, were manageable. Pomalidomide has orphan drug status both in the U.S. and Europe for multiple myeloma. It was approved by the U.S. Food and Drug Administration as Pomalyst® for the treatment of multiple myeloma last February, and recently approved in Europe in August.
Topics: Angiogenesis Inhibitors; Animals; Clinical Trials as Topic; Drug Approval; Drug Evaluation, Preclinical; Hematopoietic Stem Cell Transplantation; Humans; Multiple Myeloma; Thalidomide; United States; United States Food and Drug Administration
PubMed: 24086951
DOI: 10.1358/dot.2013.49.9.2017031 -
British Journal of Haematology Feb 2020
Topics: Dexamethasone; Humans; Lenalidomide; Multiple Myeloma; Thalidomide; Treatment Failure
PubMed: 31566715
DOI: 10.1111/bjh.16214 -
Drugs Apr 2014Oral pomalidomide (Imnovid® [EU]; Pomalyst® [USA]) in combination with dexamethasone (in the EU), is approved in several countries for the treatment of adult patients... (Review)
Review
Oral pomalidomide (Imnovid® [EU]; Pomalyst® [USA]) in combination with dexamethasone (in the EU), is approved in several countries for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on the last therapy (or progression within the last 60 days in the USA). The key therapeutic mechanisms of action of pomalidomide, a thalidomide analogue, reside in its immunomodulatory, antiproliferative and anti-angiogenic effects. In the pivotal, multinational phase II MM-002 and phase III MM-003 trials, pomalidomide plus low-dose dexamethasone was effective and had a manageable safety and tolerability profile in adult patients with relapsed and refractory multiple myeloma who had received at least two prior antimyeloma therapies, including at least 2 cycles of both lenalidomide and bortezomib. Moreover, compared with high-dose dexamethasone, treatment with pomalidomide plus low-dose dexamethasone significantly prolonged progression-free survival, overall survival and time to disease progression, and improved overall response rates in the intent-to-treat population. In general, improvements in these clinical outcomes with pomalidomide plus low-dose dexamethasone treatment were also observed in subgroups of patients, including those refractory to lenalidomide, bortezomib or both drugs, those who had received several prior antimyeloma therapies, patients with renal impairment, elderly patients and those with a high-risk cytogenetic profile. Thus, combination therapy with pomalidomide plus low-dose dexamethasone is an important emerging treatment option for use as salvage therapy in patients with relapsed and refractory multiple myeloma.
Topics: Administration, Oral; Adult; Aged; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Disease Progression; Disease-Free Survival; Dose-Response Relationship, Drug; Humans; Multiple Myeloma; Recurrence; Survival Rate; Thalidomide
PubMed: 24590685
DOI: 10.1007/s40265-014-0196-6 -
La Revue de Medecine Interne Sep 2015Once characterized by a very poor outcome, multiple myeloma (MM) now has a significantly prolonged survival, with major improvements allowed by the use of "novel... (Review)
Review
Once characterized by a very poor outcome, multiple myeloma (MM) now has a significantly prolonged survival, with major improvements allowed by the use of "novel agents": proteasome inhibitors (first-in-class bortezomib) and immunomodulatory compounds (IMiDs; first-in-class thalidomide and lenalidomide). However, the vast majority - if not all - of patients with MM ultimately end up being refractory to all existing drugs, including these efficient novel agents. There is a clear unmet medical need in this situation, which warrants the development of the next generation of proteasome inhibitors and IMiDs, as well as new drug classes. This review focuses on pomalidomide, the next generation IMiD, recently approved by the US FDA and the EMA for patients with relapsed or refractory MM who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on their last therapy.
Topics: Antineoplastic Agents; Clinical Trials as Topic; Humans; Molecular Conformation; Multiple Myeloma; Structure-Activity Relationship; Thalidomide
PubMed: 26257103
DOI: 10.1016/j.revmed.2015.04.007 -
Drug Design, Development and Therapy 2017Multiple myeloma is a very heterogeneous disease with variable survival. Despite recent progress and the widespread use of new agents, patients with relapsed and... (Review)
Review
Multiple myeloma is a very heterogeneous disease with variable survival. Despite recent progress and the widespread use of new agents, patients with relapsed and refractory disease have a poor outcome. Immunomodulatory drugs play a key role in both the front-line and the relapsed/refractory setting. The combination of pomalidomide (POM) and dexamethasone is safe and effective in relapsed and refractory patients, even in those with high-risk cytogenetic features. Furthermore, it can be used in most patients without the need to adjust according to the degree of renal failure. In order to further improve the results, POM-based triplet therapies are currently used. This article highlights the most relevant issues of POM and POM-based combinations in the relapsed/refractory multiple myeloma setting, from a pharmacological and clinical point of view.
Topics: Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Drug Design; Humans; Immunologic Factors; Multiple Myeloma; Survival Rate; Thalidomide
PubMed: 28860711
DOI: 10.2147/DDDT.S115456