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3332 Comparative Effectiveness of Daratumumab Monotherapy Versus a Real-World Historical Control from the Czech Republic in Heavily Pretreated and Highly Refractory Multiple Myeloma Patients

Myeloma: Therapy, excluding Transplantation
Program: Oral and Poster Abstracts
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster II
Sunday, December 4, 2016, 6:00 PM-8:00 PM
Hall GH (San Diego Convention Center)

Roman Hájek1, Tomas Jelinek, MD2*, Vladimir Maisnar, MD, PhD3*, Ludek Pour4*, Ivan Spicka, MD PhD5,6*, Jiri Minarik, MD, PhD7, Evzen Gregora, MD8*, Petr Kessler, MD9*, Michal Sykora, MD10*, Hana Frankova, MD11*, Dagmar Adamova, MD12*, Marek Wróbel13*, Peter Mikula, MD14*, Jiri Jarkovsky, MSc, PhD15*, Xenia Gatopoulou16*, Sarka Vesela17*, Joris Diels, PhD18*, Hervé Besson, PhD18*, Lucie Brozova, MSc15* and Tetsuro Ito19*

1Department of Hematooncology, University Hospital Ostrava Faculty of Medicine, Ostrava, Czech Republic
2Department of Haematooncology, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
34th Department of Internal Medicine – Hematology, Faculty Hospital and Charles University in Hradec Králové, Hradec Kralove, Czech Republic
4Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine Masaryk University, Brno, Czech Republic
5First Internal Clinic – Clinic of Hematology, General University Hospital, Prague, Czech Republic
6First Faculty of Medicine, Charles University, Prague, Czech Republic
7Department of Hemato-Oncology, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic
8Department of Internal Medicine and Hematology, University Hospital Kralovske Vinohrady, Prague, Czech Republic
9Department of Hematology and Transfusion Medicine, Pelhrimov Hospital, Pelhrimov, Czech Republic
10Department of Clinical Hematology, Hospital Ceske Budejovice, Ceske Budejovice, Czech Republic
11Department of Hematology, General Hospital Liberec,, Liberec, Czech Republic
12Department of Clinical Hematology, Silesian Hospital Opava, Opava, Czech Republic
13Complex Oncology Center Novy Jicin, Novy Jicin, Czech Republic
14Department of Clinical Hematology, General Hospital Havirov, Havirov, Czech Republic
15Institute of Biostatistics and Analyses, Faculty of Medicine and Faculty of Science, Masaryk University, Brno, Czech Republic
16Janssen Health Economics & Market Access EMEA, Athens, Greece
17Janssen – Cilag s.r.o, Prague
18Janssen Health Economics & Market Access EMEA Statistics & Modelling, Beerse, Belgium
19Janssen Health Economics & Market Access EMEA, High Wycombe, United Kingdom

BACKGROUND: The European Commission has granted conditional approval to daratumumab (DARA) as monotherapy in adult patients (pts) with relapsed or refractory multiple myeloma (MM) whose prior therapy included a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) and who have demonstrated disease progression on the last therapy. DARA was approved under an accelerated assessment based on single-arm phase 2 studies. Outcomes in these heavily pretreated pts in a real-world (RW) setting can provide evidence on the relative treatment efficacy of DARA versus physician’s choice (PC).

AIMS: To perform an adjusted comparison of overall survival (OS) and progression-free survival (PFS) for DARA monotherapy versus PC, as observed in a RW historical cohort of heavily pretreated and highly refractory MM pts from the Czech Republic using pt-level data.

METHODS: Using RW longitudinal pt chart data from the Registry of Monoclonal Gammopathies (RMG) of the Czech Myeloma Group, pts with ≥2 prior lines of therapy previously exposed to both a PI and an IMiD were identified. Pt-level data from the RMG were pooled from pivotal DARA monotherapy studies (pts treated with DARA 16 mg/kg). Pts in the RMG could contribute information to the analysis for multiple lines of therapy, with baseline defined as the date of initiation of the actual treatment line. For the definition of PFS, missing data for the date of disease progression for pts in the RMG who initiated subsequent therapy were replaced by the conservative proxy of the date of initiation of the next treatment. OS and PFS were analysed using a Kaplan-Meier analysis. To adjust for confounding variables, a multivariate Cox proportional hazards regression was developed that included age, gender, beta-2 microglobulin levels (β2M : <3.5/3.5-5.5/>5.5 g/L), albumin levels (<3.5/≥3.5 g/L), line of therapy (3-13), prior exposure to pomalidomide/carfilzomib, refractory status (none/double/triple/quadruple), and incidence of thrombocytopenia (defined as platelet counts <150.000 per µL) as covariates. Predicted PFS and OS curves for the RMG cohort were derived from the multivariate model.

RESULTS: From the RMG database, we identified 971 treatment lines in 463 pts previously exposed to both a PI and an IMID (n=206 in third line, n=256 in fourth line, n=203 in fifth line, n=307 in ≥sixth line). The dates of treatment initiation for the RMG pts ranged from March 2006 to March 2015. The most frequent treatment regimens were lenalidomide (33.4%), chemotherapy (18.1%), bortezomib (13.6%), thalidomide (8.0%), and bortezomib+thalidomide (5.3%). The number of pts treated with carfilzomib (2.5%) and pomalidomide (2.4%) was limited. DARA-treated pts (N=148) differed from the RMG cohort in median age (64 vs 62 years), median prior lines of therapy (5 vs 4), prior exposure to carfilzomib (41.2% vs 0.3%) and pomalidomide (55.4% vs 0.6%), thrombocytopenia incidence (46.9% vs 18.0%), and ≥triple refractory status (64.2% vs 5.3%). Median observed PFS and OS for DARA versus PC were 4.0 and 5.6 months, respectively, for PFS and 20.1 and 11.9 months, respectively, for OS. Older age, male sex, low albumin levels, high β2M levels, thrombocytopenia incidence, and double/triple/quadruple refractory status were all independent, statistically significant risk factors for mortality. Albumin levels, β2M levels, thrombocytopenia incidence, and refractory status were also predictive of PFS. The adjusted hazard ratio (95% confidence interval) for OS and PFS for DARA versus PC was 0.35 (0.22-0.56) and 0.79 (0.56-1.12), respectively. Figure 1 represents the predicted survival curves for the RMG cohort that were derived from the multivariate model, comparing observed PFS/OS versus predicted with DARA treatment.


This adjusted treatment comparison suggests a significant improvement in OS and a numerical improvement in PFS for DARA compared to RW historical control data in heavily pretreated/highly refractory MM pts. The lower PFS benefit estimate for DARA compared to OS may be partly explained by limitations in the availability and comparability of data regarding progressive disease in the RMG cohort compared to clinical trial data. Adjusted comparisons between trial data and historical cohorts can provide useful insights to clinicians and reimbursement decision makers on relative treatment efficacies in the absence of head-to-head comparison studies for DARA monotherapy.


Disclosures: Hájek: Amgen: Honoraria, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding. Spicka: BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Millenium: Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Gatopoulou: Janssen Health Economics & Market Access EMEA: Employment. Vesela: Janssen Cilag s.r.o., Czech Republic: Employment. Diels: Johnson & Johnson: Employment, Equity Ownership. Besson: Janssen: Employment. Ito: Janssen: Employment, Equity Ownership.

*signifies non-member of ASH