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Background: As lenalidomide becomes increasingly established for upfront treatment of multiple myeloma, patients refractory to this drug represent a population with an unmet need. The combination of pomalidomide, bortezomib, and dexamethasone has shown promising results in phase 1/2 trials of patients with relapsed or refractory multiple myeloma. We aimed to assess the efficacy and safety of this triplet regimen in patients with relapsed or refractory multiple myeloma who previously received lenalidomide., Methods: We did a randomised, open-label, phase 3 trial at 133 hospitals and research centres in 21 countries. We enrolled patients (aged ≥18 years) with a diagnosis of multiple myeloma and measurable disease, an Eastern Cooperative Oncology Group performance status of 0-2, who received one to three previous regimens, including a lenalidomide-containing regimen for at least two consecutive cycles. We randomly assigned patients (1:1) to bortezomib and dexamethasone with or without pomalidomide using a permutated blocked design in blocks of four, stratified according to age, number of previous regimens, and concentration of β 2 microglobulin at screening. Bortezomib (1·3 mg/m 2 ) was administered intravenously until protocol amendment 1 then either intravenously or subcutaneously on days 1, 4, 8, and 11 for the first eight cycles and subsequently on days 1 and 8. Dexamethasone (20 mg [10 mg if age >75 years]) was administered orally on the same days as bortezomib and the day after. Patients allocated pomalidomide received 4 mg orally on days 1-14. Treatment cycles were every 21 days. The primary endpoint was progression-free survival in the intention-to-treat population, as assessed by an independent review committee. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered at ClinicalTrials.gov, number NCT01734928; patients are no longer being enrolled., Findings: Between Jan 7, 2013, and May 15, 2017, 559 patients were enrolled. 281 patients were assigned pomalidomide, bortezomib, and dexamethasone and 278 were allocated bortezomib and dexamethasone. Median follow-up was 15·9 months (IQR 9·9-21·7). Pomalidomide, bortezomib, and dexamethasone significantly improved progression-free survival compared with bortezomib and dexamethasone (median 11·20 months [95% CI 9·66-13·73] vs 7·10 months [5·88-8·48]; hazard ratio 0·61, 95% CI 0·49-0·77; p<0·0001). 278 patients received at least one dose of pomalidomide, bortezomib, and dexamethasone and 270 patients received at least one dose of bortezomib and dexamethasone, and these patients were included in safety assessments. The most common grade 3 or 4 treatment-emergent adverse events were neutropenia (116 [42%] of 278 patients vs 23 [9%] of 270 patients; nine [3%] vs no patients had febrile neutropenia), infections (86 [31%] vs 48 [18%]), and thrombocytopenia (76 [27%] vs 79 [29%]). Serious adverse events were reported in 159 (57%) of 278 patients versus 114 (42%) of 270 patients. Eight deaths were related to treatment; six (2%) were recorded in patients who received pomalidomide, bortezomib, and dexamethasone (pneumonia [n=2], unknown cause [n=2], cardiac arrest [n=1], cardiorespiratory arrest [n=1]) and two (1%) were reported in patients who received bortezomib and dexamethasone (pneumonia [n=1], hepatic encephalopathy [n=1])., Interpretation: Patients with relapsed or refractory multiple myeloma who previously received lenalidomide had significantly improved progression-free survival when treated with pomalidomide, bortezomib, and dexamethasone compared with bortezomib and dexamethasone. Adverse events accorded with the individual profiles of pomalidomide, bortezomib, and dexamethasone. This study supports use of pomalidomide, bortezomib, and dexamethasone as a treatment option in patients with relapsed or refractory multiple myeloma who previously received lenalidomide., Funding: Celgene., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Rising health care costs are threatening the fiscal solvency of patients, employers, payers, and governments. The Collaborative Payer Provider Model (CPPM) addresses this challenge by reinventing the role of the payer into a full-service collaborative ally of the physician. From 2010 through 2014, a Medicare Advantage plan prospectively deployed the CPPM, averaging 30,561 members with costs that were 73.6% of fee-for-service (FFS) Medicare ( p < 0.001). The health plan was not part of an integrated delivery system. After allocating $80 per member per month (PMPM) for primary care costs, the health plan had medical cost ratios averaging 75.1% before surplus distribution. Member benefits were the best in the market. The health plan was rated 4.5 Stars by the Centers for Medicare and Medicaid Services for years 1-4, and 5 Stars in study year 5 for quality, patient experience, access to care, and care process metrics. Primary care and specialist satisfaction were significantly better than national benchmarks. Savings resulted from shifts in spending from inpatient to outpatient settings, and from specialists to primary care physicians when appropriate. The CPPM is a scalable model that enables a win-win-win system for patients, providers, and payers., Competing Interests: All authors are employees and shareholders of Essence Group Holdings Company which includes Lumeris who provides services to the Essence health plan in this study. The funding organization (Essence Group) had a role in the collection of data, its analysis and interpretation, and in the right to approve or disapprove publication of the finished manuscript.

Background: The immunomodulatory agent pomalidomide in combination with low-dose dexamethasone has demonstrated efficacy and safety for the treatment of relapsed and refractory multiple myeloma (RRMM) in phase 2 and 3 trials. However, these trials enrolled very few Asian patients., Methods: This phase 2 study investigated pomalidomide plus low-dose dexamethasone in 36 Japanese patients with RRMM after ≥2 prior therapies., Results: Patients enrolled in the study had a relatively high disease burden (81 % Durie-Salmon stage II or III) and were heavily pretreated (median, 6.5 prior antimyeloma regimens). The overall response rate was 42 % (1 patient with complete response and 14 with partial response), with an additional 44 % (16 patients) achieving stable disease (SD). Response rates in patients aged ≤65 years and >65 years were 47 and 35 %, respectively. None of the five patients with extramedullary disease achieved a response, with three of them maintaining SD of short duration. Median progression-free survival was 10.1 months after a 7.7-month median follow-up, and the median overall survival was not reached. The most frequent grade ≥3 adverse events (AEs) were neutropenia (64 %), anemia (42 %), and thrombocytopenia (31 %). The most frequent nonhematologic grade ≥3 AEs were pneumonia and decreased appetite (8 % each). Adverse events in patients aged >65 years were similar to those in patients aged ≤65 years, except for a higher rate of grade ≥3 pneumonia., Conclusions: Collectively, the results of this study demonstrate that pomalidomide plus low-dose dexamethasone is an effective and safe treatment for Japanese patients with RRMM, although careful attention needs to be paid to serious infections., Trial Registration: Clinicaltrials.gov NCT02011113.

This phase 1, open-label, dose-escalation study investigated the tolerated dose (recommended dose), safety, efficacy, and pharmacokinetics of pomalidomide alone or pomalidomide plus low-dose dexamethasone in Japanese patients with refractory or relapsed and refractory multiple myeloma. Twelve patients were enrolled. Patients received pomalidomide 2 mg (Cohort 1) or 4 mg (Cohort 2) orally on day 1 and days 3-21 of a 28-day cycle. The tolerated dose of pomalidomide was determined to be 4 mg given on days 1-21 of a 28-day cycle. Efficacy outcomes with pomalidomide plus low-dose dexamethasone were consistent with those of previous studies. Responses (partial response or better) were achieved by three patients (25%; 1 [17%] in Cohort 1 and 2 [33%] in Cohort 2), and the median time to response was 6.4 months overall (9.0 months for Cohort 1 and 4.2 months for Cohort 2). The median progression-free survival was 5.5 months overall (5.1 months for Cohort 1 and not reached for Cohort 2). The most frequently occurring grade ≥3 adverse events were neutropenia (67%), anemia (25%), lymphopenia (25%), and pneumonia (25%), consistent with previous studies of pomalidomide plus low-dose dexamethasone in refractory or relapsed and refractory multiple myeloma. Further investigation of pomalidomide is recommended for Japanese patients with refractory or relapsed and refractory multiple myeloma. This study was registered with ClinicalTrials.gov (NCT01568294)., (© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.)

Purpose: Although newer, heavily promoted medications are commonly prescribed, published evidence and consensus guidelines often support the use of less expensive alternatives. This study was designed to evaluate the impact on prescription costs of a computerized decision support system (CDSS) that provides evidence-based recommendations to clinicians during the electronic prescribing process., Methods: A retrospective cohort study was performed using a pharmacy claims database. Clinicians using the CDSS were matched with a control group by pharmacy billed amount, number of patients treated, and number of new prescriptions filled during a 6-month baseline period in which neither group used the system. The primary outcome measure was the difference in prescription costs between the 2 groups after implementation of the CDSS in the intervention group., Results: Clinicians who received evidence-based messages had significantly lower prescription costs than those in the control group. The average cost per new prescription was 4.16 dollars lower (P = .02) in the intervention group, and the average cost for new and refilled prescriptions was 4.99 dollars lower (P = .01). The 6-month savings from new prescriptions and their refills are estimated to be 3,450 dollars (95% CI, 1,030-5,863 dollars) per clinician., Conclusions: Providing electronic, evidence-based decision support during the prescribing process can shift prescribing decisions toward more evidence-based care and significantly decrease primary care prescription costs.