-
PharmacoEconomics Feb 2018The National Institute for Health and Care Excellence (NICE), as part of the institute's single technology appraisal (STA) process, invited the manufacturer of... (Review)
Review
Pomalidomide with Dexamethasone for Treating Relapsed and Refractory Multiple Myeloma Previously Treated with Lenalidomide and Bortezomib: An Evidence Review Group Perspective of an NICE Single Technology Appraisal.
The National Institute for Health and Care Excellence (NICE), as part of the institute's single technology appraisal (STA) process, invited the manufacturer of pomalidomide (POM; Imnovid, Celgene) to submit evidence regarding the clinical and cost effectiveness of the drug in combination with dexamethasone (POM + LoDEX) for the treatment of relapsed and refractory multiple myeloma (RRMM) after at least two regimens including lenalidomide (LEN) and bortezomib (BOR). Kleijnen Systematic Reviews Ltd (KSR) and Erasmus University Rotterdam were commissioned as the Evidence Review Group (ERG) for this submission. The ERG reviewed the evidence submitted by the manufacturer, validated the manufacturer's decision analytic model, and conducted exploratory analyses in order to assess the robustness and validity of the presented clinical and cost-effectiveness results. This paper describes the company submission, the ERG assessment, and NICE's subsequent decisions. The company conducted a systematic review to identify studies comparing POM with comparators outlined in the NICE scope: panobinostat with bortezomib and dexamethasone (PANO + BOR + DEX), bendamustine with thalidomide and dexamethasone (BTD) and conventional chemotherapy (CC). The main clinical effectiveness evidence was obtained from MM-003, a randomized controlled trial (RCT) comparing POM + LoDEX with high-dose dexamethasone (HiDEX; used as a proxy for CC). Additional data from other studies were also used as nonrandomized observational data sources for the indirect treatment comparison of POM + LoDEX with BTD and PANO + BOR + DEX. Covariate or treatment switching adjustment methods were used for each comparison. The model developed in Microsoft Excel 2010 using a semi-Markov partitioned survival structure, submitted in the original submission to NICE for TA338, was adapted for the present assessment of the cost effectiveness of POM + LoDEX. Updated evidence from the clinical-effectiveness part was used for the survival modelling of progression-free survival and overall survival. For POM + LoDEX, the patient access scheme (PAS) discount was applied to the POM price. Three separate comparisons were conducted for each comparator, each comparison using a different dataset and adjustment methods. The ERG identified and corrected some errors, and the corrected incremental cost-effectiveness ratios (ICERs) for POM + LoDEX versus each comparator were presented: approximately £45,000 per quality-adjusted life-year (QALY) gained versus BTD, savings of approximately £143,000 per QALY lost versus PANO + BOR + DEX, and approximately £49,000 per QALY gained versus CC. The ERG also conducted full incremental analyses, which revealed that CC, POM + LoDEX and PANO + BOR + DEX were on the cost-effectiveness frontier. The committee's decision on the technology under analysis deemed that POM + LoDEX should be recommended as an option for treating multiple myeloma in adults at third or subsequent relapse of treatments including both LEN and BOR, contingent on the company providing POM with the discount agreed in the PAS.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Cost-Benefit Analysis; Dexamethasone; Humans; Lenalidomide; Multiple Myeloma; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Recurrence; Technology Assessment, Biomedical; Thalidomide
PubMed: 29086363
DOI: 10.1007/s40273-017-0581-6 -
European Journal of Haematology Jan 2022We evaluated the efficacy and safety of pomalidomide, bortezomib, and dexamethasone (PVd) vs bortezomib and dexamethasone (Vd) by age, renal function, and high-risk... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
We evaluated the efficacy and safety of pomalidomide, bortezomib, and dexamethasone (PVd) vs bortezomib and dexamethasone (Vd) by age, renal function, and high-risk cytogenetic abnormalities in lenalidomide-pretreated patients with multiple myeloma at first relapse.
METHODS
OPTIMISMM was a phase 3, multicenter, open-label, randomized study (NCT01734928; N = 559). The primary endpoint was progression-free survival (PFS).
RESULTS
Overall, 226 patients had received one prior line of therapy. PVd significantly prolonged PFS vs Vd in patients aged ≤65 years (median, 22.0 vs 13.1 months; P = .0258) and >65 years (median, 17.6 vs 9.9 months; P = .0369). Median PFS in patients with renal impairment (RI; creatinine clearance <60 mL/min) was 15.1 months with PVd vs 9.5 months with Vd (hazard ratio [HR], 0.67 [95% CI, 0.34-1.34]). In patients without RI, median PFS was 22.0 vs 13.1 months (HR, 0.45 [95% CI, 0.27-0.76]). In patients with high-risk cytogenetics, median PFS was 14.7 vs 9.9 months (HR, 0.39 [95% CI, 0.13-1.17]). PVd significantly improved overall response rate vs Vd in all subgroups. The safety profile of PVd was consistent with previous reports.
CONCLUSIONS
These findings confirmed the benefits of PVd at first relapse, including in patients with poor prognostic factors.
Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Dexamethasone; Drug Resistance, Neoplasm; Female; Humans; Lenalidomide; Male; Middle Aged; Multiple Myeloma; Prognosis; Recurrence; Retreatment; Thalidomide; Treatment Outcome
PubMed: 34496096
DOI: 10.1111/ejh.13706 -
Expert Opinion on Drug Metabolism &... Nov 2013Multiple myeloma (MM) patients who relapse, or become refractory to currently available novel agents, have limited treatment options with poor outcomes. The... (Review)
Review
INTRODUCTION
Multiple myeloma (MM) patients who relapse, or become refractory to currently available novel agents, have limited treatment options with poor outcomes. The introductions of the newer proteasome inhibitor carfilzomib and the immunomodulatory agent pomalidomide have provided new treatment strategies within the relapse setting. Pomalidomide, a novel 4-amino derived from thalidomide, was recently introduced for the treatment of MM. In addition to being immune-adjuvant with anti-inflammatory properties, pomalidomide has shown several biological activities that directly and indirectly inhibit MM cells.
AREAS COVERED
Herein, the authors review the chemistry, the mechanism of action and the pharmacokinetic properties of pomalidomide. The data reviewed within this article based on the relevant literature pertaining to pomalidomide's Phase I, II and III clinical trials.
EXPERT OPINION
Pomalidomide has shown to be a safe and active agent, both alone and in combination with dexamethasone, in heavily pretreated patients. Furthermore, pomalidomide represents an effective treatment option for relapsed/refractory patients. Results from the ongoing trials evaluating the synergistic activity of pomalidomide combined with conventional chemotherapy or novel agents look promising and may prove to be viable treatment options in the future.
Topics: Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dexamethasone; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Humans; Immunologic Factors; Multiple Myeloma; Randomized Controlled Trials as Topic; Thalidomide
PubMed: 23961770
DOI: 10.1517/17425255.2013.827169 -
The Medical Letter on Drugs and... Apr 2015
Review
Topics: Animals; Clinical Trials as Topic; Humans; Immunologic Factors; Multiple Myeloma; Thalidomide
PubMed: 25988965
DOI: No ID Found -
Vnitrni Lekarstvi 2016In the Czech Republic, pomalidomide is covered for patients with multiple myeloma (in combination with dexamethasone), in the treatment of patients with relapsed and... (Review)
Review
In the Czech Republic, pomalidomide is covered for patients with multiple myeloma (in combination with dexamethasone), in the treatment of patients with relapsed and refractory multiple myeloma, who underwent at least 2 previous treatment schedules including both lenalidomide and bortezomibe, with disease progression despite the last therapy (i.e. during the therapy or within 60 days of its end), for whom the only remaining alternative of treatment (apart from pomalidomide) is that using high-dose dexamethasone, and who are not indicated for myeloablative treatment followed by a transplant of stem cells. At our centre pomalidomide was used in 53 patients at a median age of 66 years based on this indication. Pomalidomide was administered in 1 daily dose over 21 days in 28-day cycles. Considering the risk of thromboembolism occurring in this therapy, all patients were administered a prophylactic dose of low-molecular-weight heparin. No patient achieved complete remission (Czech Republic), 5 patients (9.4 %) achieved very good partial remission (VGPR), partial remission (PR) was achieved by 16 (30.2 %) patients, a minimum therapeutic response (MR) was recorded for 6 (11.3 %) patients. The median number of administered cycles was 4.4 (1-22). 16 (28.5 %) patients received treatment for more than 6 months. The overall survival median cannot be evaluated so far due to a short follow-up period. Nonetheless it was possible to evaluate a median time interval to progression (TTP) for the patients, which amounted to 7.0 (3.8-8.2) months. These results are consistent with large registration studies where therapeutic response (at least PR) is reached by 1/3 of the patients and medians of therapeutic response range between 7-10 months. Pomalidomide is a medicine with very good tolerance which is efficient in patients with a progressing multiple myeloma.Key words: lenalidomide - multiple myeloma - pomalidomide - thalidomide.
Topics: Adult; Aged; Antineoplastic Agents; Czech Republic; Dexamethasone; Disease Progression; Female; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Multiple Myeloma; Neoplasm Staging; Remission Induction; Thalidomide; Thromboembolism
PubMed: 28139124
DOI: No ID Found -
Blood Cancer Journal May 2023
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Multiple Myeloma; POEMS Syndrome; Thalidomide
PubMed: 37253713
DOI: 10.1038/s41408-023-00859-x -
Leukemia & Lymphoma Apr 2011Thalidomide possesses potent anti-inflammatory, immunomodulatory, and antiangiogenic properties. Thalidomide combined with corticosteroids is therapeutically active in... (Review)
Review
Thalidomide possesses potent anti-inflammatory, immunomodulatory, and antiangiogenic properties. Thalidomide combined with corticosteroids is therapeutically active in multiple myeloma and myelofibrosis (MF). Lenalidomide and pomalidomide are second-generation immunomodulatory drugs (IMiDs) that were created by chemical modification of thalidomide with the intent to reduce toxicity and enhance therapeutic activity. Both drugs have also been shown to be active in the treatment of myeloma and MF. Thalidomide is US Food and Drug Administration (FDA)-approved for use in acute erythema nodosum leprosum and, in combination with dexamethasone, in newly diagnosed myeloma. Lenalidomide is approved for use in low/intermediate-1 risk myelodysplastic syndromes associated with transfusion-dependent anemia and a deletion 5q cytogenetic abnormality and, in combination with dexamethasone, in relapsed myeloma. Pomalidomide is currently not FDA-approved. Herein, we summarize what is currently known about the biologic and therapeutic effects of pomalidomide.
Topics: Antineoplastic Agents; Boronic Acids; Bortezomib; Clinical Trials as Topic; Humans; Lenalidomide; Multiple Myeloma; Primary Myelofibrosis; Protease Inhibitors; Pyrazines; Thalidomide
PubMed: 21338284
DOI: 10.3109/10428194.2011.552139 -
Critical Reviews in Oncology/hematology Oct 2013New treatment options are urgently needed for patients with relapsed multiple myeloma (MM) who are refractory to thalidomide, lenalidomide, and bortezomib therapy.... (Review)
Review
New treatment options are urgently needed for patients with relapsed multiple myeloma (MM) who are refractory to thalidomide, lenalidomide, and bortezomib therapy. Pomalidomide, a second-generation immunomodulatory agent, has been shown to exert direct antiproliferative actions on MM cells, effects on the bone-marrow microenvironment, and immunomodulation. In phase I clinical trials, pomalidomide has demonstrated promising response rates in patients with relapsed and/or refractory MM, with manageable toxicity. In phase II trials pomalidomide, 2-4 mg/daily, given continuously or on days 1-21 of a 28-day cycle, in combination with dexamethasone, has been associated with high quality and durable clinical responses in patients who are refractory to lenalidomide, bortezomib, or both. Pomalidomide appears to be well tolerated; hematologic toxicities are the most commonly reported adverse events and peripheral neuropathy is rare. Phase III trials are currently underway to determine the optimal dose and combination regimen of pomalidomide in the treatment of MM.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cell Proliferation; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Dexamethasone; Humans; Immunologic Factors; Multiple Myeloma; Thalidomide
PubMed: 23786844
DOI: 10.1016/j.critrevonc.2013.02.001 -
Leukemia & Lymphoma Jun 2019
Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Biopsy; Female; Humans; Intraocular Lymphoma; Retreatment; Thalidomide; Treatment Outcome
PubMed: 30632826
DOI: 10.1080/10428194.2018.1538508 -
Journal of Oncology Pharmacy Practice :... Jul 2020Pomalidomide is an immunomodulating agent that is used to treat relapsed and/or refractory multiple myeloma. Although the incidence of hypersensitivity with pomalidomide...
INTRODUCTION
Pomalidomide is an immunomodulating agent that is used to treat relapsed and/or refractory multiple myeloma. Although the incidence of hypersensitivity with pomalidomide is not well documented, the most common type of hypersensitivity involves a cutaneous reaction. Previous reports have successfully utilized a desensitization protocol in patients who developed hypersensitivity to pomalidomide. Here we describe a case of a patient who developed urticaria on pomalidomide and successfully underwent a desensitization using the previously reported method in a case report.
CASE REPORT
A 68-year-old woman with relapsed multiple myeloma and no known drug allergies developed urticaria a day after taking the first dose of pomalidomide.
MANAGEMENT AND OUTCOME
The patient underwent a 10-step desensitization process in the medical intensive care unit without any reported adverse events. The following day in the medical intensive care unit, the patient was able to tolerate a full dose of pomalidomide with no further reactions and was discharged with instructions to take a full dose of pomalidomide daily for 21 days out of a 28-day cycle. The patient was followed up in the outpatient clinic and noted no further reactions from pomalidomide at the three-month visit.
DISCUSSION
The 10-step desensitization protocol with pomalidomide was well tolerated in the patient with hypersensitivity to pomalidomide. Whether this approach would work in patients with more severe reactions such as anaphylaxis and angioedema is still unknown.
Topics: Aged; Desensitization, Immunologic; Drug Hypersensitivity; Female; Humans; Immunologic Factors; Multiple Myeloma; Thalidomide; Urticaria
PubMed: 31822201
DOI: 10.1177/1078155219889676