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Elotuzumab in combination with pomalidomide and dexamethasone for the treatment of multiple myeloma.Expert Review of Anticancer Therapy Nov 2019: Despite major advances in the therapeutic management of multiple myeloma (MM), it remains an incurable disease. Several combinations of monoclonal antibodies with... (Review)
Review
: Despite major advances in the therapeutic management of multiple myeloma (MM), it remains an incurable disease. Several combinations of monoclonal antibodies with novel agents are being investigated with promising results in order to prolong progression-free and overall survival.: This paper aims to critically present available data from clinical trials investigating the combination of elotuzumab with pomalidomide and dexamethasone in refractory/relapsed MM patients and determine its current role in clinical practice.: Pomalidomide-based combinations with monoclonal antibodies have been shown to be effective in patients with MM who are refractory to or have relapsed following treatment with lenalidomide and/or a proteasome inhibitor (PI). These regimens seem to be more effective than the standard combination of pomalidomide with dexamethasone alone. Taking into consideration that the vast majority of MM patients will receive upfront treatment including a PI and lenalidomide in the near future, pomalidomide-based triplets, such as elotuzumab-pomalidomide-dexamethasone, will become the standard of care in the second line of therapy.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Humans; Multiple Myeloma; Progression-Free Survival; Survival Rate; Thalidomide; Treatment Outcome
PubMed: 31679403
DOI: 10.1080/14737140.2019.1685879 -
Klinicka Onkologie : Casopis Ceske a... 2014Despite improvements in multiple myeloma therapy, the vast majority of patients continue to suffer relapses. Unfortunately, many patients event. develop disease that is... (Review)
Review
Despite improvements in multiple myeloma therapy, the vast majority of patients continue to suffer relapses. Unfortunately, many patients event. develop disease that is refractory to lenalidomide and bortezomib and have few treatment options. Pomalidomide is a potent second-generation immunomodulatory agent with direct antiproliferative, pro-apoptotic, and antiangiogenic effects, as well as modulatory effects on bone resorption and on the immune system. Pomalidomide exhibited more potent anti-myeloma activity compared with thalidomide and lenalidomide. The optimal starting dose of pomalidomide is 4 mg given orally on days 1-21 of each 28-day cycle and combination with dexamethasone produces synergistic effects. In clinical trials, pomalidomide plus low-dose dexamethasone has shown better responses, progression-free and overall survival than high-dose dexamethasone or pomalidomide alone. Pomalidomide has limited cross-resistance with lenalidomide, and the overall response rates of pomalidomide in lenalidomide/bortezomib dual-refractory patients ranged from 26 to 31%. The most common grade 3 or 4 adverse events are hematologic, consisting of neutropenia, thrombocytopenia and anemia. Pomalidomide was approved by the FDA and the EMA in patients with multiple myeloma who have received at least two prior therapies including lenalidomide and bortezomib and have demonstrated disease progression on their last therapy. We review pomalidomide mechanism of action, clinical trials in relapsed and refractory patients, and novel pomalidomide-based combinations.
Topics: Administration, Oral; Boronic Acids; Bortezomib; Dexamethasone; Disease-Free Survival; Humans; Immunologic Factors; Lenalidomide; Multiple Myeloma; Neoplasm Recurrence, Local; Neutropenia; Pyrazines; Thalidomide
PubMed: 25312708
DOI: 10.14735/amko2014318 -
Expert Review of Anticancer Therapy May 2014Despite the improvements thanks to the introduction of proteasome inhibitors and immunomodulatory drugs (IMiDs), nearly all myeloma patients eventually become refractory... (Review)
Review
Despite the improvements thanks to the introduction of proteasome inhibitors and immunomodulatory drugs (IMiDs), nearly all myeloma patients eventually become refractory to these drugs. Consequently, the outcome of these patients is very poor. Pomalidomide is a new IMiD with a similar structure to the commonly used IMiD thalidomide and lenalidomide. Pomalidomide exhibited more potent anti-myeloma activity and a similar favorable safety profile compared with thalidomide and lenalidomide. In Phase I-II studies pomalidomide plus low-dose dexamethasone demonstrated activity in myeloma patients refractory to both bortezomib and IMiDs. Based on the results of a Phase III trial, the FDA and EMA agencies granted accelerated approval to pomalidomide, which is now considered a new effective strategy for relapsed and/or refractory myeloma patients. Very promising results were obtained when pomalidomide-dexamethasone was used in combination with other compounds. This review provides updated information about pharmacokinetics, mechanism of action, resistance, clinical efficacy and safety of pomalidomide.
Topics: Clinical Trials as Topic; Humans; Immunologic Factors; Multiple Myeloma; Thalidomide
PubMed: 24738833
DOI: 10.1586/14737140.2014.906904 -
Leukemia & Lymphoma Apr 2019
Topics: Australia; Humans; Multiple Myeloma; Neoplasms, Plasma Cell; Thalidomide
PubMed: 30277106
DOI: 10.1080/10428194.2018.1516884 -
Medicine Jan 2023Pomalidomide is an immunomodulatory imide drug used in multiple myeloma and in Kaposi sarcoma.
RATIONALE
Pomalidomide is an immunomodulatory imide drug used in multiple myeloma and in Kaposi sarcoma.
PATIENT CONCERNS
A 72-years-old male, treated for multiple myeloma with dexamethasone, pomalidomide and daratumumab, presented dyspnea, hypoxemia, biological inflammatory syndrome, ground glass opacities on computed tomography scan (CT-scan) and lymphocytic and eosinophilic alveolitis, with no specific cytologic or microbiological findings, 2 months after pomalidomide initiation.
INTERVENTION AND OUTCOME
Antibiotics were started after bronchoscopy. No improvement was noted in dyspnea and biological inflammatory syndrome after 5 days of treatment. Pomalidomide was then discontinued, with continuation of Daratumumab-Dexamethasone, resulting in a rapid recovery of symptoms and CT-scan anomalies. No recurrence of dyspnea was observed during the 15 months of follow-up.
DIAGNOSES
Pomalidomide-induced lung injury.
LESSONS
Pomalidomide-induced lung injury is a rare and serious adverse event that can occur early after Pomalidomide introduction. As pomalidomide use is increasing, the identification of drug toxicity as a possible cause of lung injury appears important. We report a rapid recovery of symptoms and CT-scan anomalies after pomalidomide discontinuation.
Topics: Male; Humans; Aged; Multiple Myeloma; Lung Injury; Dexamethasone; Dyspnea; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36637962
DOI: 10.1097/MD.0000000000032473 -
Oncotarget Jun 2017The use of carfilzomib/pomalidomide single-agent or in combination with other agents in patients with refractory/relapsed multiple myeloma (RRMM) was not clearly... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The use of carfilzomib/pomalidomide single-agent or in combination with other agents in patients with refractory/relapsed multiple myeloma (RRMM) was not clearly clarified in clinical practice. We sought to compile the available clinical reports to better understand the efficacy and safety of carfilzomib (CFZ) and pomalidomide (POM).
RESULTS
Based on our research criteria, we identified 37 prospective studies that evaluated 1160 patients. Analysis of subgroup differences between carfilzomib single-agent and CFZ/DEX dual combination showed significantly(P < 0.001, I2 = 96.3%), suggesting the overall response rate (ORR) of 66% attained from CFZ/DEX dual combination seemed to be higher than that of 28% from carfilzomib single-agent. And, the same trend favoring CFZ/DEX dual combination was found in ≥VGPR and CBR analysis. The ORR of 31% attained from POM/DEX dual combination was superior to that of 19% from pomalidomide single-agent(P < 0.001, I2 = 94.4%). And, the same trend favoring POM/DEX dual combination was found in ≥VGPR and CBR analysis. However, the ORR of 83% attained from POM/BOR/DEX triplet combination was superior to that of 31% from POM/DEX dual combination(P < 0.001, I2 = 99.1%). And, the same trend favoring POM/BOR/DEX triplet combination was found in ≥VGPR analysis.
METHODS
We searched published reports including carfilzomib and (or) pomalidomide therapy for RRMM who had received bortezomib and (or) lenalidomide.
CONCLUSION
Pomalidomide/Carfilzomib plus dexamethasone seemed to attain a superior response rate compared with pomalidomide/carfilzomib single-agent. Furthermore, the combination of pomalidomide, bortezomib and dexamethasone resulted in a much higher response rate compared with pomalidomide plus dexamethasone regimen. These results needed more validation in future trials.
Topics: Antineoplastic Combined Chemotherapy Protocols; Disease Management; Drug Resistance, Neoplasm; Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Oligopeptides; Prospective Studies; Salvage Therapy; Thalidomide
PubMed: 27458170
DOI: 10.18632/oncotarget.10768 -
Pathology Oncology Research : POR 2022Pomalidomide is a third generation immunomodulatory drug in the treatment of refractory and relapsed multiple myeloma patients. Our aim was to investigate the efficacy...
Pomalidomide is a third generation immunomodulatory drug in the treatment of refractory and relapsed multiple myeloma patients. Our aim was to investigate the efficacy and safety of pomalidomide therapy in a real world setting. Eighty-six Hungarian patients were included, 45 of whom received pomalidomide ± an alkylating agent, while in 38 of them pomalidomide was combined with a proteasome inhibitor. 56 patients (65%) showed any response to the treatment with 18 complete or very good partial remissions and 38 partial remissions. At a median duration of follow-up of 18.6 months, the median progression-free survival (PFS) was 9.03 months, while the median overall survival (OS) was 16.53 months in the whole cohort. Patients with early stage disease (R-ISS 1 and 2) had better survival results than those with stage 3 myeloma ( = 0.002). Neither the number of prior treatment lines, nor lenalidomide refractoriness had a significant impact on PFS PFS was found similar between the cohort of patients with impaired renal function and the cohort without kidney involvement. During the study, eight mortal infections and two fatal bleeding complications occurred, however, mild hematologic and gastrointestinal toxicities were identified as the most frequent adverse events. The results of our investigations confirm that pomalidomide is an effective treatment option for relapsed/refractory MM, besides, the safety profile is satisfactory in subjects with both normal and impaired renal function.
Topics: Humans; Multiple Myeloma; Lenalidomide; Hungary; Proteasome Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Treatment Outcome; Alkylating Agents
PubMed: 36262875
DOI: 10.3389/pore.2022.1610645 -
Journal of Chemotherapy (Florence,... Dec 2014Pomalidomide (Pomalyst(®)) is a synthetic compound derived by modifying the chemical structure of thalidomide to improve its potency and reduce its side effects and... (Review)
Review
Pomalidomide (Pomalyst(®)) is a synthetic compound derived by modifying the chemical structure of thalidomide to improve its potency and reduce its side effects and third drug in the class of immunomodulatory drugs. Pomalidomide is under global development with Celgene Corporation, was approved by the U.S. Food and Drug Administration on February 8, 2013 to treat patients with relapsed and refractory multiple myeloma (MM) who have received at least two prior therapies including bortezomib and lenalidomide. In October 2009, it has found orphan designation for the treatment of relapsed and refractory MM by the EMA, and on August 2013, marketing authorization has issued in Europe by gaining a positive response. It inhibits myeloma cell growth and angiogenesis directly. Pomalidomide is the latest myeloma cell growth inhibitor to be approved in both USA and EU. The predominant side effects are thrombocytopenia, neuropathy, and deep vein thrombosis. Pomalidomide is also being investigated in patients with amyloidosis, prostate cancer, small cell lung cancer, pancreatic cancer, graft-versus-host disease, and Waldenstrom's macroglobulinemia. This article reviews the available information on pomalidomide with respect to its clinical pharmacology, mechanism of action, pharmacokinetics, pharmacodynamics, metabolism, pre-clinical studies, and clinical trials.
Topics: Animals; Clinical Trials as Topic; Female; Humans; Immunologic Factors; Male; Multiple Myeloma; Thalidomide
PubMed: 25004945
DOI: 10.1179/1973947814Y.0000000201 -
American Journal of Health-system... Sep 2014The pharmacology, pharmacokinetics, clinical efficacy, safety, dosage and administration, and place in therapy of pomalidomide for the management of refractory multiple... (Review)
Review
PURPOSE
The pharmacology, pharmacokinetics, clinical efficacy, safety, dosage and administration, and place in therapy of pomalidomide for the management of refractory multiple myeloma are reviewed.
SUMMARY
Pomalidomide is a second-generation immunomodulatory agent that has been approved by the Food and Drug Administration (FDA) for the management of multiple myeloma refractory to both lenalidomide and bortezomib, with or without the addition of dexamethasone. The overarching mechanism of action is thought to be antiproliferative and directly cytotoxic to malignant plasma cells in the bone marrow. Clinical trials have demonstrated both safety and efficacy with the 4-mg dose given orally on days 1-21 of a 28-day cycle with the possible addition of dexamethasone 40 mg weekly. The most common nonhematologic toxicities found in clinical trials were fatigue, pneumonia, and deep vein thrombosis. The most common hematologic toxicity was neutropenia, which was the only dose-limiting factor of pomalidomide. In order to be able to prescribe and dispense pomalidomide, physicians, patients, and pharmacies must enroll in an FDA-mandated risk evaluation and mitigation strategy program due to the drug's teratogenic effects. Future studies will evaluate the use of pomalidomide with other oncolytic agents, as well as combination regimens with proteasome inhibitors, such as bortezomib, for the management of multiple myeloma.
CONCLUSION
Pomalidomide when administered with weekly low-dose dexamethasone appears to be both safe and effective for the treatment of relapsed or refractory multiple myeloma in patients who have had disease progression after completing treatment with bortezomib, lenalidomide, or both.
Topics: Drug Resistance, Neoplasm; Humans; Immunologic Factors; Multiple Myeloma; Thalidomide
PubMed: 25147167
DOI: 10.2146/ajhp130752 -
Expert Opinion on Drug Safety 2016Pomalidomide, a derivative of thalidomide and member of the immunomodulatory drugs is licenced for use in relapsed and refractory multiple myeloma (RRMM) in Europe, USA,... (Review)
Review
INTRODUCTION
Pomalidomide, a derivative of thalidomide and member of the immunomodulatory drugs is licenced for use in relapsed and refractory multiple myeloma (RRMM) in Europe, USA, Canada and Japan.
AREAS COVERED
This review details all published trials in which pomalidomide has been used in the treatment of myeloma including phase I, II and III studies via PubMed searches for randomised control trials, observational cohort, case reports, meta-analysis and reviews. In addition abstract searches from the 2015 IMW and ASH conferences have been included. Drug safety has been a main focus with additional detail outlining the current clinical experience and treatment efficacy. Drug related toxicities and management of such events are covered in detail.
EXPERT OPINION
Pomalidomide is well tolerated and has been demonstrated to prolong progression free survival and overall survival in RRMM patients in comparison to other agents commonly used later in the disease. Treatment related toxicities are usually easily managed using treatment interruption, dose modification, prophylactic therapies and blood/platelet transfusions. There is scope for the drug to be used in combination with newer agents at disease presentation, relapse and as a long-term maintenance option. At present trials assessing its use in early disease and maintenance are lacking.
Topics: Clinical Trials as Topic; Cohort Studies; Humans; Immunologic Factors; Meta-Analysis as Topic; Multiple Myeloma; Observational Studies as Topic; Randomized Controlled Trials as Topic; Safety; Thalidomide
PubMed: 26913560
DOI: 10.1517/14740338.2016.1154039