Johan Aschan

The cost‐effectiveness of bortezomib in relapsed/refractory multiple myeloma: Swedish perspective

Objectives:u2002 To estimate the cost‐effectiveness of bortezomib (BTZ) compared with dexamethasone (DEX) and lenalidomide plus dexamethasone (LEN/DEX) for the treatment of relapsed/refractory multiple myeloma in Sweden.

Improved survival in myeloma patients: starting to close in on the gap between elderly patients and a matched normal population

The outcome for multiple myeloma patients has improved since the introduction of bortezomib, thalidomide and lenalidomide. However, studies comparing new and conventional treatment include selected patient groups. We investigated consecutive patients (n = 1638) diagnosed in a defined period and compared survival with a gender‐ and age‐matched cohort Swedish population (n = 9 340 682). Median overall survival for non‐high‐dose treated patients was 2·8 years. The use of bortezomib, thalidomide or lenalidomide in first line therapy predicted a significantly longer overall survival (median 4·9 years) compared to conventional treatment (2·3 years). Among non‐high‐dose treated patients receiving at least 2 lines with bortezomib, thalidomide or lenalidomide, 69% and 63% have survived at 3 and 5 years as compared to 48% and 22% with conventional drugs and 88% and 79% in the matched cohort populations, respectively. The median overall survival in high‐dose treated patients was 6·9 years. Of these patients, 84% survived at 3 years and 70% at 5 years as compared to 98% and 95% in the matched cohort population. Overall survival in the best non‐high‐dose treated outcome group is closing the gap with the matched cohort. Upfront use of new drugs is clearly better than waiting until later lines of treatment.

The Use of Novel Drugs Can Effectively Improve Response, Delay Relapse and Enhance Overall Survival in Multiple Myeloma Patients with Renal Impairment

Background Renal impairment is a common feature in multiple myeloma and is considered a poor prognostic factor. Aim To determine the impact of novel drugs (i.e. bortezomib, lenalidomide and thalidomide) in the treatment of myeloma patients with renal impairment. The primary endpoint was overall survival and secondary endpoints were time to next treatment and response. Methods The study population included all patients diagnosed with treatment-demanding multiple myeloma January 2000 to June 2011 at 15 Swedish hospitals. Renal impairment was defined as an estimated glomerular filtration rate under 60 mL/min/1.73 m2. Result The study population consisted of 1538 patients, of which 680 had renal impairment at diagnosis. The median overall survival in patients with renal impairment was 33 months, which was significantly shorter than 52 months in patients with normal renal function (P<0.001). Novel agents in first line improved overall survival (median 60 months) in non-high-dose treated patients with renal impairment (nu200a=u200a143) as compared to those treated with conventional cytotoxic drugs (nu200a=u200a411) (median 27 months) (P<0.001). In the multivariate analysis up front treatment with bortezomib was an independent factor for better overall survival in non-high-dose treated renally impaired patients. High-dose treated renally impaired patients had significantly better median overall survival than non-high-dose ones (74 versus 26 months) and novel drugs did not significantly improve survival further in these patients. Patients with renal impairment had both a shorter median time to next treatment and a lower response rate than those with normal renal function. However, novel drugs and high dose treatment lead to a significantly longer time to next treatment and the use of novel agents significantly improved the response rate of these patients. Conclusion High dose treatment and novel drugs, especially bortezomib, can effectively overcome the negative impact of renal impairment in patients with multiple myeloma.

Ibrutinib for chronic lymphocytic leukemia: international experience from a named patient program

After first approval of ibrutinib for patients with B-cell malignancies in the US, an international named patient program (NPP) was initiated to provide ibrutinib to patients before local country approval. In this observational retrospective analysis of data collected from the NPP, estimated time on treatment and its relationship with baseline characteristics were analyzed for patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Ibrutinib outcomes were compared with those from the phase III RESONATETM study. Our findings suggest that ibrutinib is effective and well tolerated in the real world, with time on treatment similar to the clinical trial setting; younger age and complete response (CR)/partial response (PR) to prior therapy were predictive of longer time on treatment. In B-cell malignancies such as CLL, Bruton’s tyrosine kinase (BTK) is a rational target for therapy because it is needed for B-cell receptor signaling, plays a key role in Bcell maturation, and is overexpressed. Benefits of ibrutinib, a first-in-class, once-daily, oral, covalent inhibitor of BTK, have been demonstrated in phase II and III studies across multiple B-cell malignancies. Ibrutinib is approved in the EU, US and elsewhere to treat patients with CLL, Waldenström’s macroglobulinemia and relapsed/refractory mantle cell lymphoma. It is also indicated for marginal zone lymphoma in the US. NPPs enable controlled access to treatments that have shown a positive benefit-risk ratio for life-threatening conditions, in response to unsolicited requests by physicians and on behalf of patients, before the drug is licensed or commercially available in their country. NPPs can provide data on the clinical use, treatment duration, efficacy and relative safety of a drug in a real-world context. After the first approval of ibrutinib in the US in November 2013, an international ibrutinib NPP was initiated for patients with B-cell malignancies who met respective phase III trial eligibility criteria. Here we describe an observational retrospective analysis of data from patients with relapsed/refractory CLL enrolled in the international ibrutinib NPP from March 2014 through October 2015, to estimate time on treatment and explore related patient characteristics. Time on ibrutinib treatment in the international NPP was compared with the phase III RESONATETM (PCYC-1112) study of ibrutinib versus ofatumumab in patients with relapsed/refractory CLL. Inclusion criteria for the NPP were based on RESONATETM: age ≥18 years; confirmed diagnosis of CLL/small lymphocytic lymphoma (including patients with 17p deletion); Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of <2; relapsed/refractory disease after ≥1 prior therapy, defined as failure to achieve a PR with, or documented progression after, the most recent treatment regimen. Participation was approved by the local independent ethics committee or institutional review board as needed, and the enrolling physician obtained patients’ informed consent. Patients received oral ibrutinib 420 mg once daily continuously until progressive disease (PD) or unacceptable toxicity. Disease evaluations and safety monitoring were conducted by enrolling physicians, according to local standard of care. Ibrutinib was provided through the NPP until commercially available, at which point patients were transferred to commercial drug if appropriate, and follow up stopped. Data on the ordering/reordering of ibrutinib were collected. Treatment start and stop (discontinuation) dates were entered by the physician via a simple questionnaire on the Janssen Managed Access portal (MAcWeb; if not entered, reordering data were censored at the date of last ibrutinib supply). Patient baseline characteristics and reasons for stopping orders were collected from physicians at enrollment and treatment discontinuation, respectively, also via MAcWeb. Kaplan-Meier analysis and Cox proportional hazards regression were used to estimate time on treatment. Relationships between baseline characteristics and time on treatment were explored via multivariate analyses, included categorical variables of age, sex, number of prior therapy lines, time since CLL diagnosis, PD on prior therapy in the past 3 months, CR or PR to last therapy, relapsed disease and refractory disease. In total, 2908 patients with CLL from 30 countries were enrolled in the NPP. Baseline demographic and disease characteristics are shown in Table 1. Naïve comparison with patient baseline characteristics of the RESONATETM study ibrutinib arm suggests median age and proportion of males were similar, however, the proportion of patients with ≥3 prior lines of therapy was higher in the NPP (63% vs. 53% for NPP vs. RESONATETM). Fewer patients in the NPP relapsed after purine analogues (70% vs. 85%, respectively) or anti-CD20 therapy (68% vs. 94%, respectively). The estimated proportion of patients on treatment at 12 months was 77.3% (95% confidence interval [CI]: 74.7, 79.6) in the NPP, similar to RESONATETM (actual 12month time on treatment rate, 81.5%; 95% CI: 75.3, 86.3). Time on treatment for the international CLL NPP and RESONATETM populations were not statistically different (hazard ratio, 1.20 [95% CI: 0.86, 1.67]) (Figure 1). The median duration of follow up was 5.78 (range, 0.0318.73) months in the NPP, and 9.4 (range, 0.1-16.6) months in RESONATETM. In the multivariate analysis, younger age (<50 years) and achievement of CR/PR as a response to prior therapy were independent factors significantly associated with longer time on treatment. Having a CLL diagnosis for >5 years

PCN100 SIMILARITIES AND DIFFERENCES IN TREATMENT PATTERNS AND RESOURCE UTILISATION FOR MULTIPLE MYELOMA: A COMPARISON BETWEEN 4 NORDIC COUNTRIES

PCN96 A TRIAL-BASED ASSESSMENT OF THE COST-UTILITY OF BEVACIZUMAB AND CHEMOTHERAPY VERSUS CHEMOTHERAPY ALONE FOR ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC) Goulart B, Ramsey S Pharmaceutical Outcomes Research and Policy Program, Seattle, WA, USA, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA OBJECTIVES: Patients with advanced NSCLC have a poor prognosis—with median overall survival of less than one year. A randomized clinical trial (RCT) of bevacizumab plus chemotherapy vs. chemotherapy alone demonstrated a significant (2-month) improvement in median survival. However, a cost-effectiveness analysis of this therapy has not been published. Based on the RCT results, we performed a costutility and cost-effectiveness analysis to evaluate the cost-effectiveness of bevacizumab added to chemotherapy in patients with advanced NSCLC. METHODS: We developed a Markov model to project quality-adjusted life years (QALYs) and direct medical costs from a US health care payer perspective in patients treated with bevacizumab plus chemotherapy vs. chemotherapy alone. Survival and toxicity data for the model came from the RCT (ECOG 4599). We obtained utilities from a literature search and unit costs from Medicare. We discounted QALYs and costs at 3% per year. We addressed uncertainty with one-way and probabilistic sensitivity analyzes. RESULTS: Compared to chemotherapy alone, bevacizumab and chemotherapy increased mean life expectancy by 0.23 years and mean QALYs by 0.13, at an incremental lifetime cost of US

PCN48 THE COST-EFFECTIVENESS OF BORTEZOMIB FOR RELAPSED/REFRACTORY MULTIPLE MYELOMA IN SWEDEN

71,000 per patient. The projected incremental cost-effectiveness ratios (ICERs) were US

PMC87 COMPARING CHART REVIEW AND MODIFIED DELPHI PANEL RESOURCE DATA COLLECTION METHODS: THE COST OF TREATMENT FOR MULTIPLE MYELOMA IN SWEDEN

309,000/life-year gained and US

Optimal Treatment Sequencing In Multiple Myeloma: An Exploratory Modeling Approach

557,000/QALY gained, respectively. Sensitivity analysis showed that the cost-effectiveness was most sensitive to the number of cycles of bevacizumab, its unit cost, and the utility in stable disease state during treatment. CONCLUSIONS: Based on commonly cited costeffectiveness thresholds, bevacizumab is not projected to be cost-effective for these trial patients from a payer perspective (but without accounting for any possible price assistance programs). An analysis from the societal perspective could generate different results. These findings might help decision-makers to make informed decisions about resource allocation for advanced NSCLC care.

Is Multiple Myeloma a Chronic Disease? : A Population Based Study Comparing 1843 Patients to a Matched Swedish Population

s A45 and IFN-alpha alone (US

Is Renal Impairment Still a Poor Prognostic Marker in Myeloma Care? : A Population Based Study Including 1542 Patients

29,000). The ICER’s per PFM and OS resulted in US