Ianalumab plus Eltrombopag in Immune Thrombocytopenia

Author(s): Adam Cuker, M.D.¹; Thomas Stauch, M.D.²; Nichola Cooper, M.D.³; Hanny Al-Samkari, M.D.⁴; Marc Michel, M.D.⁵; Waleed Ghanima, M.D., Ph.D.^6,7; Patrick Urban, M.D., Ph.D.⁸; Justyna Fronczek, Ph.D.⁸; Matthew Foster, M.D.⁹; Marine Weill, M.Sc.⁸; Lei Zhang, M.D.¹⁰; Ming Hou, M.D., Ph.D.¹¹; Thomas Zander, M.D.¹²; Azizan Sharif, M.Med.¹³; Jing Sun, M.D.¹⁴; Uttam Kumar Nath, D.M.¹⁵; Roger Schutgens, M.D., Ph.D.¹⁶; Elena Rossi, M.D.¹⁷; Lien Deleu, M.D.¹⁸; Libor Červinek, M.D., Ph.D.¹⁹; Jae-Ho Yoon, M.D., Ph.D.²⁰; Hung Chang, M.D.^21,22,23; Theera Ruchutrakool, M.D.²⁴; Masaki Iino, M.D., Ph.D.²⁵; Tatsunori Goto, M.D., Ph.D.²⁶; Francesco Zaja, M.D.²⁷; the VAYHIT2 Investigators*;

Source: DOI: 10.1056/NEJMoa2515168

Dr. Maen Hussein's Thoughts

Ianalumab, a monoclonal antibody targeting B cells was assessed in adults with primary Immune Thrombocytopenia (ITP) and an insufficient response or a relapse after first-line glucocorticoid therapy at a dose of 9 mg or 3 mg per kilogram of body weight or placebo once monthly for 4 months with eltrombopag which was tapered to discontinuation by week 24. The time to treatment failure was significantly longer with ianalumab plus eltrombopag than with placebo plus eltrombopag with HR of 0.55 in the 9-mg group and 0.58 in the 3-mg group. The percentage of patients with a stable response at 6 months was significantly higher in the 9-mg group than in the placebo group (62% vs. 39%; P=0.045).

BACKGROUND

Current second-line treatments for immune thrombocytopenia (ITP) require long-term administration. Ianalumab, a monoclonal antibody targeting B cells, is being assessed as a short-course second-line therapy in ITP.

METHODS

In this phase 3, randomized, double-blind trial, we assigned, in a 1:1:1 ratio, adults with primary ITP and an insufficient response or a relapse after first-line glucocorticoid therapy to receive ianalumab a dose of 9 mg or 3 mg per kilogram of body weight or placebo once monthly for 4 months. Eltrombopag, an oral thrombopoietin-receptor agonist, was administered once daily in each group according to local prescribing information; the dose was tapered until discontinuation by the end of week 24 in eligible patients. The primary end point was freedom from treatment failure, as determined in a time-to-event analysis, with treatment failure defined by a platelet count of less than 30×109 per liter more than 8 weeks after randomization, initiation of rescue therapy more than 8 weeks after randomization, initiation of new ITP therapy, inability to taper or discontinue eltrombopag because of an inadequate platelet count, or death from any cause, whichever occurred first. The key secondary end point was a stable response 6 months, defined by a platelet count of least 50×109 per liter in least 75% of the measurements between weeks 19 and 25 without use of rescue therapy or new ITP therapy. Safety was assessed. Research Summary Ianalumab plus Eltrombopag in Immune Thrombocytopenia

RESULTS

A total of 152 patients underwent randomization: 50 to the 9-mg ianalumab group, 51 to the 3-mg ianalumab group, and 51 to the placebo group. The estimated probability of being free from treatment failure 12 months was 54% (95% confidence interval [CI], 39 to 67) in the 9-mg group, 51% (95% CI, 36 to 64) in the 3-mg group, and 30% (95% CI, 18 to 43) in the placebo group. The time to treatment failure was significantly longer with ianalumab plus eltrombopag than with placebo plus eltrombopag; the estimated hazard ratio for treatment failure (ianalumab vs. placebo) was 0.55 (P=0.04) in the 9-mg group and 0.58 (P=0.045) in the 3-mg group. The percentage of patients with a stable response 6 months was significantly higher in the 9-mg group than in the placebo group (62% vs. 39%; P=0.045). The overall frequency of adverse events during the treatment period was generally similar in the three groups. The frequency of serious adverse events was 16% in the 9-mg group, 6% in the 3-mg group, and 4% in the placebo group.

CONCLUSIONS

Ianalumab plus eltrombopag led to a longer time to treatment failure than placebo plus eltrombopag. (Funded by Novartis; VAYHIT2 ClinicalTrials.gov number, NCT05653219.)

Author Affiliations

¹Department of Medicine and Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia; ²Department of Internal Medicine II, Hematology and Oncology, University Hospital Jena, Jena, Germany; ³Centre for Haematology, Department of Immunology and Inflammation, Imperial College, London; ⁴Division of Hematology Oncology, Massachusetts General Hospital, Harvard Medical School, Boston; ⁵Department of Internal Medicine, Henri Mondor University Hospital, Assistance Publique–Hôpitaux de Paris, Paris-Est Créteil University, Créteil, France; ⁶Østfold Hospital Trust, Kalnes, Norway; ⁷University of Oslo, Oslo; ⁸Novartis Pharma, Basel, Switzerland; ⁹Novartis Pharmaceuticals, East Hanover, NJ; ¹⁰Department of Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China; ¹¹Department of Hematology, Qilu Hospital of Shandong University, Jinan, China; ¹²Department of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University Hospital of Cologne, Cologne, Germany; ¹³Department of Medicine, Sultanah Aminah Johor Bahru Hospital, Johor Bahru, Malaysia; ¹⁴Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China; ¹⁵Department of Medical Oncology–Hematology, All India Institute of Medical Sciences, Rishikesh, India; ¹⁶Center for Benign Hematology, Thrombosis and Hemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; ¹⁷Department of Radiological and Hematological Sciences, Universita Cattolica del Sacro Cuore and Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome; ¹⁸Department of Hematology, AZ Delta, Roeselare, Belgium; ¹⁹Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic; ²⁰Department of Hematology, Catholic Hematology Hospital, Seoul St. Mary’s Hospital, College of Medicine, Catholic University of Korea, Seoul, South Korea; ²¹Division of Hematology–Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; ²²School of Medicine, Chang Gung University, Taoyuan, Taiwan; ²³Center of Hemophilia and Coagulation Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; ²⁴Division of Hematology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; ²⁵Department of Hematology and Hematopoietic Stem Cell Transplantation, Yamanashi Prefectural Central Hospital, Kofu, Japan; ²⁶Department of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital, Nagoya, Japan; ²⁷Dipartimento di Scienze Mediche, Chirurgiche e della Salute, University of Trieste and Department of Hematology, Azienda Sanitaria Universitaria Giuliano-Isontina, Trieste, Italy

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