Cost-Effectiveness of Sequential Treatment Containing Crizotinib for Non Small Cell Lung Cancer (ALK+) Patients

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threshold.  Conclusions: This study proves that daratumumab is a cost-effective therapy for the treatment of MM in the Italian NHS, compared to SOC for patients who have received ≥ 2 prior lines of therapy, including a PI or an IMiD, or who were double refractory to both. PCN171 Cost-Effectiveness of Additional Human Papillomavirus Vaccination Programmes, in The Netherlands Setiawan D1, Westra TA2, Daemen T3, Nijman HW3, Wilschut JC3, Postma MJ1 of Groningen, Groningen, The Netherlands, 2GlaxoSmithKline, Zeist, The Netherlands, 3University Medical Center Groningen, Groningen, The Netherlands

1University

Objectives: Here we aimed to assess the cost-effectiveness of three different vaccination scenarios (i) increased coverage of the existing programme, (ii) vaccination of girls at an older age, and (iii) vaccination of teenage boys.  Methods: A dynamic model was used to assess the clinical and economic consequences of the existing programme with and without the above mentioned alternative scenarios. Costs and health effects (life years and QALYs) of the alternative scenarios were compared with the outcomes of the existing programme. In sensitivity analyses the robustness of the model-predicted outcomes were assessed.  Results: The cost-effectiveness of the existing HPV vaccination programme was estimated at € 7,500 per QALY gained. Furthermore, the cost-effectiveness of a catch-up programme was estimated at above € 50,000 per QALY gained. Taking into account the vaccine-induced cross-protection, small differences in cost-effectiveness between the bivalent (i.e. € 5,900/QALY), quadrivalent (i.e. € 7,000/QALY) and nonavalent (i.e. € 5,400/QALY) vaccine were found, reflecting likely cost effective situations. Furthermore, in addition to the existing programme, the cost-effectiveness of an increased coverage up to 100%, assuming lifelong protection, was below € 20,000 per QALY gained. With the vaccination coverage of 50%, the vaccination of girls at 20 years of age was likely cost-effective (i.e. € 20,000-50,000/QALY) in combination with the existing programme. With the current vaccination coverage, the addition of vaccination for boys is likely not cost effective in the Netherlands. The cost-effectiveness was most sensitive to duration of vaccine-induced protection, discounting and coverage of the existing vaccination programme.  Conclusions: From a health-economic perspective, alternative vaccination programmes in addition to the existing programme should be considered. Cost-effectiveness of catchup programmes or vaccination for boys were highly sensitive to the coverage of the existing programme. PCN172 Subcutaneous vs Intravenous Administration of Trastuzumab in Her2+ Breast Cancer Patients: A Montenegrin Cost-Minimization Analysis Todorovic V1, Durutovic I1, Ivanovska A2, Zajmovic A2 Center Montenegro, Podgorica, Montenegro, 2Hoffmann La Roche Ltd., Podgorica, Montenegro

1Clinical

Objectives: The aim of this economic analysis is to compare the total cost of subcutaneous trastuzumab (SC-TRA) vs intravenous trastuzumab (IV-TRA) for HER2positive breast cancer patients at the Oncology Department at Clinical Center of Montenegro. HannaH study showed that SC-TRA has a pharmacokinetic profile and efficacy non-inferior to standard IV-TRA and is a valid alternative for the treatment of eligible breast cancer patients.  Methods: A cost-minimization analysis was performed using data from market research from 2016 and an administration time analysis. Total time and cost of both types of TRA administration were quantified in a time horizon of over 18 cycles therapy course. 55 patients (mean weight 72 kg) from the Oncology clinic were included in this analysis. Patients were HER2-positive and received the drug in the adjuvant (72 patients) or metastatic (19 patients) setting. Drug cost (direct costs) included only drug treatment per mean patient weight, and non- drug (indirect) costs included chair time treatments, daily hospital fee, active healthcare professional time, consumable disposals, patients’ transport and sick leaves. The model accounted the 5% wastage of IV-TRA administration. Unit costs were obtained utilizing official (Monetengrin Dug Agency (CALIMS) and clinic pharmacy) publicly available data and they were expressed in local currency (Euro) with discount aplied for SC-TRA.  Results: Direct drug related costs per mean patient weight were up to 8,3 % savings for SC-TRA and up to 9,9% also for SC-TRA when indirect costs included. The results of the analysis were most sensitive to patient weight, daily hospital fee and % of wastage in IV treated patients. Mean savings (preparation and administration) in time with SC-TRA were 55 min.  Conclusions: SC-TRA is time and cost-saving therapy for HER2+ breast cancer patients in Montenegro. PCN173 Cost Minimization Analysis of The Selective Aromatase Inhibitors; Anastrozole, Versus Letrozole and Exemestane for The Management of Breast Cancer From Patient Perspective in Egypt Assal RA German University in Cairo, Cairo, Egypt

Objectives: Breast cancer (BC) is the second most common type of cancer worldwide and the most frequent cancer among women (approx. 25%) according to WHO. Globally, 1.67 million new BC cases were diagnosed in 2012, with an increased incidence after menopause. Since most BC subtypes are hormone-related, national comprehensive cancer network (NCCN)-2017 guidelines recommended the use of third-generation anti-estrogen aromatase-inhibitor endocrine therapy in early-stage post-menopausal women having hormone receptor-positive BC. The aromataseinhibitors; Anastrozole, Letrozole, and Exemestane lower the risk of BC recurrence and metastasis when used as initial first-line adjuvant therapy in addition to tamoxifen. Those drugs have shown similar anti-tumor efficacy and toxicity profiles in randomized studies in adjuvant and preoperative settings, rendering them equivalent choices for the management of BC. Thus, this study aimed at performing cost minimization analysis for Anastrozole, versus Letrozole and Exemestane as a 5-year initial

20 (2017) A399–A811

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adjuvant therapy for the management of post-menopausal BC from patient’s perspective in Egypt.  Methods: Direct medical costs are reported in Egyptian pounds (EGP) (1 USD= 18.14 EGP). The single daily doses for Anastrozole, Letrozole, and Exemestane tablets are 1 mg, 2.5 mg, and 25 mg, respectively. Discounting was conducted for a treatment course of 5 years. One-way sensitivity analysis was performed where costs were varied with a range of ± 25%.  Results: Total costs for Anastrozole, Letrozole, and Exemestane were EGP18,071, EGP19,993, and EGP36,910, respectively. Thus, Anastrozole is the least expensive drug when compared to Letrozole and Exemestane for the management of BC. Sensitivity analysis showed that the study was insensitive to change using a range of ±25% in drugs’ costs.  Conclusions: Anastrozole, Letrozole, and Exemestane are equivalent choices as adjuvant therapies in postmenopausal breast cancer patients. Therefore, having the lowest cost, Anastrozole is the most preferred option when compared to Letrozole, and Exemestane for the management of breast cancer from patient’s perspective. PCN174 Economic Evaluation of Dasatinib Compared To Nilotinib as Second Line Treatment of Chronic Myeloid Leukemia in Greece Gourzoulidis G1, Vassilopoulos G2, Gialama F1, Kourlaba G1, Diamantogiannis F3, Maniadakis N4 LP, Athens, Greece, 2University of Thessaly Medical School, Larissa, Greece, 3BristolMyers Squibb Hellas, Athens, Greece, 4National School of Public Health, Athens, Greece 1Evroston

Objectives: To conduct an economic evaluation of Dasatinib versus Nilotinib as a second line treatment (SLT) of Chronic Myeloid Leukemia (CML) in Greece.  Methods: A systematic literature review was conducted to synthesize the evidence concerning the efficacy of alternative therapies. The review revealed that the available data do not indicate any difference in terms of efficacy between Dasatinib and Nilotinib in SLT. As such, a cost-minimization analysis was performed to compare Dasatinib and Nilotinib. The analysis was conducted from a third-party payer perspective with one-year time horizon. Resource consumption data were obtained from a local expert, using a questionnaire developed for the purpose of the study and were combined with unit costs (in € 2016) obtained from official sources. Because the time horizon did not exceed 1 year, no discounting was necessary for cost outcomes. One-way sensitivity analysis (OWSA) was undertaken to test the robustness of the results.  Results: The analysis showed that in SLT, the total annual cost per patient with Dasatinib and Nilotinib was estimated at € 34,086 and € 34,937, respectively, resulting in a cost-saving of € 850.61, for the former. The OWSA showed that the results were more sensitive to the drug acquisition cost of Dasatinib and Nilotinib.  Conclusions: Based on available clinical and local resource utilization and unit cost data, the present study suggests that, in a one-year time horizon, Dasatinib may be a cost-saving treatment option compared to other alternative therapies in SLT of CML patients in Greece. PCN175 Expanded Access To Pembrolizumab from Cost-Savings Generated by Biosimilar Filgrastim (BIOSIM-FIL) in The Prophylaxis of Chemotherapy-Induced (FEBRILE) Neutropenia (CIN/FN): Simulation Study McBride A1, Balu S2, Campbell K2, Bikkina M2, MacDonald K3, Abraham I4 1University of Arizona Cancer Center, Tucson, AZ, USA, 2Sandoz, Inc., Princeton, NJ, USA, 3Matrix45, LLC, Tucson, AZ, USA, 4University of Arizona, Tucson, AZ, USA

Objectives: CIN/FN prophylaxis with BIOSIM-FIL may offer cost-savings over reference filgrastim (FIL) and pegfilgrastim (PEGFIL). The objectives were to [1] simulate, for a 20,000 patient panel, cost-savings achieved from CIN/FN prophylaxis with BIOSIM-FIL over FIL and PEGFIL; [2] estimate the budget-neutral expanded access to pembrolizumab treatment from these cost-savings; [3] determine the number-needed-to-convert (NNC) to purchase one additional pembrolizumab treatment.  Methods: Simulation analysis using 3Q2016 average selling price (ASP; US$) cost for one patient for one chemotherapy cycle with 5, 7, 11, or 14 days of prophylaxis. For a 20,000-patient panel, we calculated [1] cost-savings (US $) accrued from 5/7/11/14d prophylaxis converted to BIOSIM-FIL; [2] expanded access afforded by these cost-savings to pembrolizumab (1 administration Q3W for 2 years at $153,673); [3] NNC for one additional pembrolizumab treatment.  Results: Per-cycle costsavings from BIOSIM-FIL over FIL were $327.00 (5d), $457.80 (7d), $719.40 (11d), and $915.60 (14d). For 20,000 patients, conversion from FIL to BIOSIM-FIL yields savings of (rounded) $6,450,000 (5d), $9,156,000(7d), $14,388,000 (11d), $18,312,000 (14d). These savings provide expanded access to 2y of pembrolizumab treatment to 43 (5d BIOSIM-FIL regimen), 60 (7d), 94 (11d), and 119 (14d) patients. The NNC is 470 (5d), 336 (7d), 214 (11d), and 168 (14d). As conversion-related savings relative to PEGFIL decline as daily injections increase, for 20,000 patients, conversion from PEGFIL to BIOSIMFIL yields savings of $55,893,600 (5d), $47,177,600 (7d), $29,745,600 (11d), $16,671,600 (14d). These savings provide expanded access to 2y of pembrolizumab treatment to 364 (5d BIOSIM-FIL regimen), 307 (7d), 194 (11d), and 108 (14d) patients. The NNC is 55 (5d), 65 (7d), 103 (11d), and 184 (14d).  Conclusions: Conversion from reference FIL and PEGFIL to BIOSIM-FIL not only yields significant savings, especially when converting from PEGFIL, but these savings can be applied to procure therapeutic cancer care with pembrolizumab on a budget-neutral basis. PCN176 Cost-Effectiveness of Sequential Treatment Containing Crizotinib for Non Small Cell Lung Cancer (ALK+) Patients Sabater Cabrera E1, Puente J2, Oyagüez I3, García-Campelo R4, Reguart N5, Rodriguez D6, Cobo M7, Soto J8, Moran M8 1Pharmacoeconomics & Outcomes Research Iberia, Madrid, Spain, 2Hospital Clinico San Carlos, Madrid, Spain, 3Pharmacoeconomics & Outcomes Research Iberia, Pozuelo de Alarcón, Spain, 4hospital Universitario A Coruña, A Coruña, Spain, 5Hospital Clinic de Barcelona, Barcelona, Spain, 6Complejo Hospitalario Universitario Insular- Materno Infantil, Las Palmas de Gran Canaria, Spain, 7Hospital Regional de Malaga (Carlos Haya), Malaga, Spain, 8Pfizer Spain, Alcobendas, Spain

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Objectives: Crizotinib is approved in first-line for non-small cell lung cancer (NSCLC) ALK positive patients. This study aimed to estimate the cost-effectiveness of two different containing Crizotinib sequential treatments, in Spain.  Methods: A Markov model based on potential treatment lines in NSCLC patients, was developed to estimate health benefits (life year gained-LYG and quality adjusted life year-QALY) and total costs in a hypothetical patient cohort during a lifetime period. Sequence 1:crizotinib as first-line (crizotinib-> ceritinib -> pemetrexed -> Best Supportive Care [BSC]) was compared to Sequence 2:crizotinib positioned in second-line (pemetrexed-> platinum-> crizotinib-> ceritinib-> BSC). Transitions between treatment lines were based on progression free survival (PFS) data observed in clinical trials. Overall survival (OS) was used to reflect the probability of death. Parametric functions adjusted to PFS and OS Kaplan-Meier curves, were used to extrapolate data from trials along the simulation period. Frequency of grade 3/4 adverse events (AE) per individual treatment and utilities were derived from literature. Total cost estimation (€ ,2016) included drug with official deduction (ex-factory list price for crizotinib and 0 for ceritinib as it is free currently for the Spanish NHS), chemotherapy administration (only pemetrexed), disease and AE management costs. An oncologists’ board validated and provided health resource consumption data for BSC and disease and AE management. Annual discount rate (3%) was applied. Several sensitivity analysis (SA) were performed.  Results: Sequence 1 resulted in a more effective option, yielding 0.88 LYG and 0.68 additional QALY than sequence 2. Total costs for sequence 1 resulted € 194,460 compared to € 149,415 for sequence 2. The incremental cost-effectiveness ratios were € 51,178/LYG and € 66,486/QALY gained with crizotinib first-line-sequence versus the sequence 2, crizotinib in second-line. SA results confirmed the model’s robustness.  Conclusions: A treatment sequence based on crizotinib in first-line resulted in a cost-effective option for NSCLC patients (ALK+) in Spain, compared to an alternative sequence with crizotinib in second-line. PCN177 Cost Utility Analysis (CUA) of Nivolumab Compared To Everolimus for The Treatment of Metastatic Renal Cell Carcinoma (RCC) in Australia Liew D1, Patten N2, Tan M2, Kim H2 University, Melbourne, Australia, 2Bristol-Myers Squibb Australia, Mulgrave, Australia

1Monash

Objectives: International five-year survival rates for metastatic kidney and renal pelvis cancer are estimated at between 12-20%, indicating significant unmet clinical need for effective therapies. Currently, everolimus is a subsidised treatment option in Australia for patients who have progressive disease following first-line treatment with a tyrosine kinase inhibitor. Nivolumab is the first immunotherapy agent explored in RCC (CheckMate-025) and this study sought to assess the cost utility of nivolumab versus everolimus.  Methods: A 3-state (clinical progression free, clinical disease progression, dead) Markov model was developed with 2-week cycles. Individual patient data from the pivotal study directly informed the health state transition probabilities until a minimum follow-up of 14 months. Thereafter, survival curves were extrapolated to 10 years, followed by convergence of the curves at 20 years. Australian specific health state utilities, drug costs and disease management costs were drawn from published sources. A range of sensitivity analyses were undertaken to test the robustness of the results of the modelled economic evaluation.  Results: Nivolumab added an average of 0.78 life years (LYs) and 0.65 quality adjusted life years (QALYs) per person at an additional cost of US$45,000 (discounted), resulting in ICERs of US$58,000/LY saved and US$69,000/QALY saved. The sensitivity analysis showed that the result was most sensitive to the time horizon and duration of treatment. However, the ICER was stable and generally stayed within +/-10% of the base case for most of the scenarios in tested in the sensitivity analyses.  Conclusions: Nivolumab represents a cost-effective alternative to everolimus, with potential to improve quality of life and survival for RCC patients in Australia. PCN178 Cost-Effectiveness of Nivolumab in Combination with Ipilimumab in First-Line Treatment of Advanced Melanoma in Sweden: Analysis Using 28-Month Overall Survival from Checkmate 067 Baker T1, Paly VF1, Sabater J2, Holmberg C3, Hultberg M4, Lundström J3, Minacori R5, Chirita O6 1ICON, New York, NY, USA, 2Bristol-Myers Squibb, Princeton, NJ, USA, 3Bristol-Myers Squibb, Bromma, Sweden, 4PAREXEL International, Stockholm, Sweden, 5PAREXEL International, London, UK, 6Bristol-Myers Squibb, Uxbridge, Middlesex, UK

Objectives: The objective of this study was to evaluate the cost-effectiveness of nivolumab in combination with ipilimumab (Nivo+Ipi) compared to current therapeutic alternatives in first-line treatment of patients with advanced melanoma regardless of biomarker status in Sweden from a payer perspective using recently reported 28-month survival data from the CheckMate 067 Phase III trial.  Methods: A three-state partitioned survival model was developed from projections of overall survival and progression free survival based on a network meta-analysis which considers time-varying hazard ratios to estimate accrued quality-adjusted survival and costs over a 15-year time horizon. The analysis considered nivolumab monotherapy as the key comparator but also included ipilimumab, pembrolizumab, dabrafenib, dabrafenib + trametinib, vemurafenib + cobimetinib, and dacarbazine. Drug acquisition, administration, follow-up, subsequent therapy and adverse event costs were obtained via published sources and expert input. Adverse event frequencies were collected from the Checkmate 067 trial and published literature. Utility weights were estimated from the Checkmate 067 trial, based on UK tariffs. A 3% discount rate was applied to costs and utilities. Results were presented as incremental cost-utility ratios (ICURs).  Results: Nivo+Ipi was projected to have the greatest accrued survival among the competing treatments with 5.07 LYs and 3.93 QALYs and also the highest total costs (1,941,848 kr). The comparisons vs. nivolumab, resulted in an ICUR of 319,045 kr. Pairwise ICURs for Nivo+Ipi vs. other treatments ranged from 112,002 kr per QALY (vs. pembrolizumab) to 578,393 kr per QALY (vs. dacarbazine).  Conclusions: The analysis highlighted that Nivo+Ipi is associated with the highest gain in qualityadjusted survival accompanied by higher costs compared to the current therapeutic

alternatives. ICUR results indicated that Nivo+Ipi is likely to be a cost-effective option in the first-line treatment of advanced melanoma in Sweden. PCN179 A Cost-Utility Analysis Comparing Two Sequences of Treatment for First-Line Chemotherapy in Metastatic Prostate Cancer (MCRPC): Cabazitaxel Followed by Docetaxel Versus Docetaxel Followed by Cabazitaxel Schwager M1, Fizazi K1, Zaghdoud N1, Delva R2, Gravis Mescam G3, Baciarello G1, Theodore C4, Gross Goupil M5, Bompas E6, Joly F7, Tazi Y8, L’Haridon T9, N’guyen T10, Barthelemy P11, Culine S12, Berdah J13, Deblock M14, Beuzedoc P15, Flechon A16, Cheneau C17, Martineau G1, Borget I18 1Gustave Roussy, Villejuif, France, 2ICO Paul Papin, Angers, France, 3Institut Paoli-Calmettes, Marseille, France, 4Hôpital Foch, Suresnes, France, 5CHU Bordeaux, Bordeaux, France, 6ICO Centre René Gauducheau, Saint-Herblain, France, 7Centre François Baclesse, Caen, France, 8Clinique Sainte-Anne, Strasbourg, France, 9CHD Vendée, La Roche Sur Yon, France, 10CHRU Besançon, Besançon, France, 11CHRU Strasbourg, Strasbourg, France, 12Hôpital Saint Louis, Paris, France, 13Clinique Sainte-Marguerite, Hyères, France, 14Institut de Cancérologie de Lorraine, Vandoeuvrelès-Nancy, France, 15Institut Curie, Paris, France, 16Centre Léon Bérard, Lyon, France, 17CHRU Brest, Brest, France, 18Institut Gustave Roussy, Villejuif, France

Objectives: Docetaxel and Cabazitaxel are taxane chemotherapy approved in men with mCRPC after they demonstrated improved survival in first and second line respectively. If recent data suggested similar efficacy, these two taxanes have different safety profile and unit price, raising the question of their administration sequence. A cost-utility analysis comparing two sequences of treatment (Cabazitaxel followed by Docetaxel versus Docetaxel followed by Cabazitaxel) for first-line chemotherapy in metastatic prostate cancer was performed in the French context, using data from the CABADOC randomized trial.  Methods: The CABADOC study is a randomized trial with a cross-over design. Patients were randomized to receive either Docetaxel 75mg/m²/q3w x 4 followed by Cabazitaxel 25mg/m²/q3w x 4, or the reverse sequence. The economic analysis included a prospective collection of resources consumed (chemotherapy, hospitalizations, transportation, nurses and consultations) and utility data (using the EQ-5D questionnaire administered before cycle 1, cycle 5 and at the end of chemotherapy) alongside the trial. Costs were evaluated from the French collective perspective and horizon time was limited from the randomization date to the end of 2nd sequence chemotherapy. The ICER was calculated and sensitivity analyses were conducted.  Results: From June 2014 to October 2016, 195 patients (median age of 70 years) were randomized in 17 centers. Patients received 3.8 ± 0.7 and 3.2 ± 1.5 cycles of chemotherapy during the first and the second period, respectively. The sequence Docetaxel-Cabazitaxel appears to be more effective (mean QALY per patient of 0.353 ± 0.025 versus 0.328 ± 0.063) and less expensive (mean cost per patient of 17 350 €  ± 2955 versus 17 862 €  ± 2320) as compared to the sequence Cabazitaxel-Docetaxel.  Conclusions: The sequence of treatment with Docetaxel followed by Cabazitaxel appears the optimal one for first line chemotherapy in metastatic prostate cancer from a cost-utility standpoint. NCT: NCT02044354. PCN180 The Cost-Effectiveness of Pegaspargase for First-Line Treatment of Acute Lymphoblastic Leukaemia: A Cost-Utility Analysis Basu S1, Lin PL2, Saha V3 1Shire, London, UK, 2Shire Pharmaceuticals, Cambridge, MA, USA, 3University of Manchester, Manchester, UK

Objectives: A cost-utility analysis was conducted to evaluate the cost-effectiveness of pegaspargase (PEG-ASP) compared to native asparaginase (Native-ASP) as part of antineoplastic combination therapy for newly diagnosed acute lymphoblastic leukaemia (ALL) in the United Kingdom.  Methods: A combined decision-tree and health-state-transition Markov model was developed to compare treatment sequences starting with PEG-ASP versus Native-ASP, followed by a switch to Erwiniaderived asparaginase (ERW-ASP) in cases of hypersensitivity. Although ERW-ASP is not first-line in the UK, alternative switching scenarios are clinically possible; therefore all scenarios were modelled. Paediatric (≤ 25 years) and adult (26-65 years) patients were modelled separately using UKALL2003 and UKALL14 protocols, respectively. Survival and hypersensitivity risk parameters were based on published data and clinical input. In the base-case analysis, overall survival and event-free survival were assumed equivalent for PEG-ASP (1,000 IU/m2 dosing, per UKALL protocols), Native-ASP, and ERW-ASP, In scenario analyses, 2,500 IU/m2 dosing for PEG-ASP (per SmPC) was examined. Total cost and total quality-adjusted life-years (QALYs) over the lifetime horizon were estimated. Incremental cost-effectiveness ratios (incremental costs/QALYs gained) were calculated. Deterministic and probabilistic sensitivity analyses were performed to evaluate the influence of input parameters and model robustness.  Results: The base-case scenario demonstrated that PEGASP followed by ERW-ASP was cost-effective compared to strategies starting with Native-ASP or ERW-ASP. Treatment with PEG-ASP was less expensive than NativeASP (£7,871 vs £12,612) with higher QALYs (17.34 vs 17.29, respectively), with total cost savings of £4,741 and total QALY gain of 0.05 for PEG-ASP followed by ERW-ASP in newly diagnosed ALL patients. Scenario analyses highlighted the robustness of the cost-effectiveness results. Differences in the cost-effectiveness results between PEG-ASP and Native-ASP were driven primarily by the difference in hypersensitivity rates.  Conclusions: This analysis demonstrates that PEG-ASP, as part of multidrug chemotherapy, is a cost-effective treatment option compared to Native-ASP for children, young adults, and adults with newly diagnosed ALL. PCN181 Potential Therapeutic and Economic Value of Risk-Stratified Treatment as Initial Treatment of Multiple Myeloma in Europe Gaultney JG1, Ng T1, Uyl-de Groot CA2, Sonneveld P3, van Beers EH4, van Vliet MH4, Redekop WK2 1Mapi Group, London, UK, 2Erasmus University Rotterdam, Rotterdam, The Netherlands, 3Erasmus MC, Rotterdam, The Netherlands, 4SkylineDx, Rotterdam, The Netherlands