Isatuximab Subcutaneous by On-Body Injector Versus Isatuximab Intravenous Plus Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Phase III IRAKLIA Study

Author(s): Sikander Ailawadhi, MD [email protected]¹; Ivan Špička, MD²; Andrew Spencer, MBBS³; Jin Lu, MD⁴; Albert Oriol, MD, PhD⁵; Silvia Ling, MBBS, PhD⁶; Fredrik Schjesvold, MD⁷; Alejandro Berkovits, MD⁸; Marek Hus, MD, PhD⁹; Chunrui Li, MD¹⁰; Meletios-Athanasios Dimopoulos, MD^11,12; Péter Rajnics, MD^13,14; Sevgi Kalayoğlu Beşışık, MD¹⁵; Vania Hungria, MD, PhD¹⁶; Maria del Rosario Custidiano, MD¹⁷; Gurdeep Parmar, MBBS, MD¹⁸; Xavier Leleu, MD¹⁹; Fei Li, MD, PhD²⁰; Claudio Cerchione, MD, PhD²¹; Cesar Gomez, MD, PhD²²; Tadao Ishida, MD²³; Maria Victoria Mateos, MD, PhD²⁴; Tondre T. Buck, MD²⁵; Richard LeBlanc, MD²⁶; Jiří Minařík, MD X²⁷; Hartmut Goldschmidt, MD²⁸; Rick Zhang, PhD²⁹; Dorothée Sémiond, PharmD, PhD³⁰; Florence Suzan, MD³¹; Maya Stefanova-Urena, MD²⁹; Victorine Koch, PharmD, MSc³¹; Philippe Moreau, MD³²;

Source: https://doi.org/10.1200/JCO-25-00744

Dr. Maen Hussein's Thoughts

Guess who’s coming as an option beyond AI (OBI)? Yes—this study showed no safety concerns and demonstrated comparable efficacy.

PURPOSE

To report the results of the multicenter, open-label IRAKLIA trial (ClinicalTrials.gov identifier: NCT05405166) of isatuximab subcutaneous (SC) versus intravenous (IV), plus pomalidomide and dexamethasone, in relapsed/refractory multiple myeloma (MM), to our knowledge, the first phase III MM trial using an on-body injector (OBI).

METHODS

Patients with ≥1 prior line of therapy were randomly assigned 1:1 to Isa OBI (1,400 mg) or IV (10 mg/kg) once weekly in cycle (C)1 and then every 2 weeks, plus pomalidomide (4 mg once daily, day [D]1-21) and dexamethasone (40 mg once weekly [age ≥75: 20 mg]) and treated until progression, unacceptable toxicity, or patient request. Coprimary end points were overall response rate (ORR; noninferiority margin, 0.839) and Isa Ctrough (C6D1 predose; noninferiority margin, 0.8). Noninferiority of OBI versus IV was demonstrated if both coprimary end points achieved noninferiority.

RESULTS

IRAKLIA randomly assigned 531 patients (OBI, n=263; IV, n=268). After 12-month median follow-up, the ORR was 71.1% (OBI) and 70.5% (IV; relative risk, 1.008 [95% CI, 0.903 to 1.126]; lower CI exceeded noninferiority margin). The mean (standard deviation) C6D1 Ctrough was 499 (259) μg/mL (OBI) and 340 (169) μg/mL (IV). The Ctrough geometric mean ratio (90% CI) was 1.532 (1.316 to 1.784); lower CI exceeded noninferiority margin. Grade ≥3 treatment-emergent adverse event incidences were 81.7% (OBI) and 76.1% (IV); infusion reaction incidences were 1.5% and 25.0%. Injection site reactions occurred in 0.4% of OBI injections (all grade 1-2); 99.9% of injections completed without interruption.

CONCLUSION

IRAKLIA demonstrated efficacy and pharmacokinetic noninferiority between Isa OBI and IV. No unexpected safety signal was observed, with excellent local tolerability of Isa OBI. Efficacy and safety were comparable with Isa IV in ICARIA-MM, except the lower OBI infusion reaction rate. These results support potential use of the OBI, designed to improve practice efficiency.

Author Affiliations

¹Division of Hematology/Oncology, Mayo Clinic, Jacksonville, FL; ²1st Department of Medicine—Department of Hematology, First Faculty of Medicine, Charles University and General Hospital, Prague, Czech Republic; ³Malignant Haematology and Stem Cell Transplantation Service, Alfred Health-Monash University, Melbourne, VIC, Australia; ⁴Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing, China; ⁵Institut Català d'Oncologia and Josep Carreras Research Institute, Hospital Germans Trias i Pujol, Barcelona, Spain; ⁶Sydney Adventist Hospital, Wahroonga, NSW, Australia; ⁷Oslo Myeloma Center, Department of Hematology, Oslo University Hospital, Oslo, Norway; ⁸Inmunocel, Las Condes, Santiago, Chile; ⁹Department of Hematooncology and Bone Marrow, Medical University of Lublin, Lublin, Poland; ¹⁰Department of Hematology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; ¹¹Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece; ¹²Department of Medicine, Korea University, Seoul, South Korea; ¹³Mór Kaposi Teaching Hospital, Department of Hematology, Kaposvár, Hungary; ¹⁴Faculty of Health Sciences, Institute of Diagnostics, University of Pécs, Pécs, Hungary; ¹⁵Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey; ¹⁶Department of Hematology and Oncology, Clínica São Germano, São Paulo, Brazil; ¹⁷Servicio de Hematología y Trasplante Hematopoyético Instituto Alexander Fleming, Buenos Aires, Argentina; ¹⁸Illawarra Cancer Care Centre, Wollongong, NSW, Australia; ¹⁹Service d'Hématologie et Thérapie Cellulaire, CHU and CIC Inserm 1402, Poitiers Cedex, France; ²⁰Human Institute, ShanghaiTech University, Shanghai, China; ²¹Hematology Unit, Istituto Romagnolo per lo Studio dei Tumori ‘Dino Amadori’ – IRST IRCCS, Meldola (FC), Italy; ²²Haematology Unit, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, United Kingdom; ²³Japanese Red Cross Medical Center, Tokyo, Japan; ²⁴Hospital Universitario de Salamanca-Instituto Biosanitario de Salamanca, Salamanca, Spain; ²⁵Spartanburg Medical Center, Center for Hematology/Oncology, Spartanburg, SC; ²⁶Hematology-Oncology and Cell Therapy University Institute, Hôpital Maisonneuve-Rosemont Research Center, Université de Montréal, Montréal, QC, Canada; ²⁷Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacký University and University Hospital Olomouc, Olomouc, Czech Republic; ²⁸Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany; ²⁹Sanofi, Bridgewater, NJ; ³⁰Sanofi, Cambridge, MA; ³¹Sanofi R&D, Vitry-sur-Seine, France; ³²Hematology Department, CHU Nantes, Nantes, France

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