Adjusted comparison of daratumumab monotherapy versus real-world historical control data from the Czech Republic in heavily pretreated and highly refractory multiple myeloma patients

Abstract

Objectives: We conducted an adjusted comparison of progression-free survival (PFS) and overall survival (OS) for daratumumab monotherapy versus standard of care, as observed in a real-world historical cohort of heavily pretreated multiple myeloma patients from Czech Republic.

Methods: Using longitudinal chart data from the Registry of Monoclonal Gammopathies (RMG) of the Czech Myeloma Group, patient-level data from the RMG was pooled with pivotal daratumumab monotherapy studies (GEN501 and SIRIUS; 16 mg/kg).

Results: From the RMG database, we identified 972 treatment lines in 463 patients previously treated with both a proteasome inhibitor and an immunomodulatory drug. Treatment initiation dates for RMG patients were between March 2006 and March 2015. The most frequently used treatment regimens were lenalidomide-based regimens (33.4%), chemotherapy (18.1%), bortezomib-based regimens (13.6%), thalidomide-based regimens (8.0%), and bortezomib plus thalidomide (5.3%). Few patients were treated with carfilzomib-based regimens (2.5%) and pomalidomide-based regimens (2.4%). Median observed PFS for daratumumab and the RMG cohort was 4.0 and 5.8 months (unadjusted hazard ratio [HR], 1.14; 95% confidence interval [CI], 0.94–1.39), respectively, and unadjusted median OS was 20.1 and 11.9 months (unadjusted HR, 0.61; 95% CI, 0.48–0.78), respectively. Statistical adjustments for differences in baseline characteristics were made using patient-level data. The adjusted HRs (95% CI) for PFS and OS for daratumumab versus the RMG cohort were 0.79 (0.56–1.12; p = .192) and 0.33 (0.21–0.52; p < .001), respectively.

Conclusions: 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 daratumumab monotherapy.

Keywords:

• Czech Republic
• multiple myeloma
• daratumumab
• matching adjusted indirect comparison
• treatment outcomes

Transparency

Declaration of funding

This study was sponsored by Janssen Global Services LLC.

Author contributions: J.D., X.G., Š.V., H.B. and T.I. were involved in generating the analysis. All authors were involved in the interpretation of the data, and in providing critical input to the development of the manuscript. All authors provided final approval of the version to be published, and all authors agree to be accountable for all aspects of the work.

Declaration of financial/other relationships

V.M. has disclosed that he consulted for Amgen, Bristol-Myers Squibb, Celgene, Janssen-Cilag and Takeda; received grant support from The Binding Site; received honoraria from Amgen, Bristol-Myers Squibb, Celgene and Janssen-Cilag; and served on advisory boards for Amgen, Bristol-Myers Squibb, Celgene, Janssen-Cilag and Takeda. I.Š. has disclosed that he consulted for BMS, Celgene, Janssen-Cilag and Amgen; received honoraria from BMS, Celgene, Janssen-Cilag, Amgen and Millennium; and has been involved in advisory boards for BMS, Celgene and Janssen-Cilag. J.D., X.G., Š.V., H.B. and T.I. have disclosed that they are employees of Janssen, and J.D. and T.I. hold stock in Johnson & Johnson. R.H. has disclosed that he consulted for Takeda Pharmaceutical, Novartis, Onyx and Bristol-Myers Squibb; received grant support from Takeda Pharmaceutical, Novartis, Amgen and Celgene; received honoraria from Takeda Pharmaceutical, Novartis, Onyx, Bristol-Myers Squibb and Amgen; and served on advisory boards for Takeda Pharmaceutical, Novartis, Onyx and Bristol-Myers Squibb. T.J., L.P., J.M., E.G., P.K., M.S., H.F., D.A., M.W., P.M., J.J. and L.B. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

A peer reviewer on this manuscript declares research support from Celgene, Janssen, Chugai, Novartis and BMS; advisory board participation for Janssen, Celgene, Novartis, Amgen, Takeda and BMS; and speaker’s bureau from Celgene, Janssen, Novartis, Chugai and BMS. Other CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose.

Acknowledgements

Medical writing and editorial support were provided by Jason Jung PhD of MedErgy and were funded by Janssen Global Services LLC. The authors would like to thank to all physicians, nurses, data managers and data quality managers in the Registry of Monoclonal Gammopathies who participated in this collaborative work: Jakub Radocha MD, Renáta Smetanová, and Renáta Rybářová (4th Department of Internal Medicine – Hematology, Faculty Hospital and Charles University in Hradec Kralove); Marta Krejčí MD, Zdenek Adam MD, Viera Sandecka MD, Eva Vetešníková, and Martina Vyhňáková (Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine Masaryk University); Lenka Zahradová MD, Hana Plonkova MD, Daniel Hořínek, and Eva Jakšíková (Department of Hematooncology, University Hospital Ostrava and Faculty of Medicine University of Ostrava); Vlastimil Ščudla MD, Tomáš Pika MD and Iveta Slánská (Department of Hemato-Oncology, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacky University Olomouc); Jan Straub MD, Martina Jermoljevova and Petra Szendzielarzová (1st Medical Department – Clinical Department of Haematology of the First Faculty of Medicine and General Teaching Hospital Charles University, Prague); Petr Pavlíček MD and Kateřina Klásková (Department of Internal Medicine and Hematology, University Hospital Kralovske Vinohrady, Prague); Adriana Heindorfer MD, Lenka Walterová MD, and Jaroslava Karlová (Department of Hematology, Hospital Liberec); Lukáš Stejskal MD and Jelena Štohanzlová (Department of Hematology, Hospital Opava); Martin Brejcha MD (Department of Hematology, Hospital Novy Jicin); David Starostka MD and Natálie Lenčová MD (Departent of Clinical Haematology, Hospital in Havirov); Věra Šilerová and Jana Procházková (Department of Hematology and Transfusion Medicine, Hospital Pelhrimov); Hana Šuléřová (Department of Clinical Hematology, Hospital Ceske Budejovice); Jarmila Obernauerová MD, Dagmar Lesáková, and Lucie Ulmanová MD (Department of Hematology and Transfusion, Klaudians Hospital, Mladá Boleslav); Iveta Mareschova, Andrea Janotova, Jana Smejkalova and Daniel Hořínek (Czech Myeloma Group office, quality data management). The authors would also like to thank Finlay MacDougall for leading on data acquisition and interpretation, Catrina Richards for working on the protocol and data acquisition and Sarah Rabhi for working on data acquisition and interpretation.