The Phase 2b LUMINA 2 study found haemoglobin responses with rilzabrutinib in previously treated warm autoimmune haemolytic anaemia, with 64% responding by Week 24.
Written By: Anshu Gupta, PharmD
Reviewed By: Pharmacally Editorial Team
A Phase 2b study published in The Lancet Haematology evaluated rilzabrutinib in adults with warm autoimmune haemolytic anaemia (wAIHA), a rare blood disorder characterised by immune-mediated destruction of red blood cells. The disease can cause anaemia, fatigue, impaired quality of life and an increased risk of thromboembolic complications.
LUMINA 2 (NCT05002777) was a multicentre, single-arm, open-label study that evaluated oral rilzabrutinib in adults with previously treated wAIHA who had relapsed, were refractory to, or were dependent on corticosteroids. Patients received rilzabrutinib with or without concomitant corticosteroids. Although patients with primary or systemic lupus erythematosus-associated wAIHA were eligible, no patients with SLE-associated wAIHA were ultimately enrolled.
The study included 22 patients in Part A. Rilzabrutinib was administered orally at 400 mg twice daily for 24 weeks. Patients achieving the Part A overall haemoglobin response endpoint and completing 24 weeks could continue into Part B.
Overall Haemoglobin Response at Week 24
The primary endpoint for Part A was overall haemoglobin response by Week 24, defined as either a haemoglobin response or complete response without recent transfusion or rescue medication.
A haemoglobin response required an increase of at least 2 g/dL from baseline without biochemical resolution of haemolysis. Complete response required haemoglobin of at least 11 g/dL in women or 12 g/dL in men, with no evidence of haemolysis.
Among the 22 patients in Part A, 14 (64%; 95% CI, 41–83) achieved an overall haemoglobin response by Week 24. This included 13 patients (59%) with a haemoglobin response and three (14%) with complete response. Two of the three patients with complete response also met the response criterion, meaning the categories were not mutually exclusive.
The median time to the first overall haemoglobin response among all patients was 99 days, while patients who ultimately responded or achieved complete response had a median time to first response of 50 days. Nine patients (41%) also achieved the study’s durable haemoglobin response definition during the first 24 weeks.
Responses Maintained During Extended Treatment
Fifteen patients entered Part B for continued treatment. The primary endpoint for Part B was durable haemoglobin response, defined as haemoglobin of at least 10 g/dL, with an increase of at least 2 g/dL from Part A baseline maintained across three consecutive evaluable visits between after Week 24 and Week 50, without transfusion or rescue medication during the specified assessment period.
Twelve of 15 patients (80%) achieved a durable haemoglobin response. Median haemoglobin concentrations among these patients ranged from 11.5 to 12.1 g/dL during Part B through Week 50. The median duration of haemoglobin response among Part B patients was 274 days.
The study also reported reductions in haemolysis markers. Increased haemoglobin concentrations were accompanied by reductions in lactate dehydrogenase, reticulocytes and total bilirubin.
Fatigue and Corticosteroid Findings
Beyond haemoglobin responses, patients experienced clinically meaningful improvements in fatigue, measured using the Functional Assessment of Chronic Illness Therapy-Fatigue scale. Improvements of at least three points were considered clinically meaningful and were observed during both Parts A and B.
The study also allowed stable concomitant corticosteroid treatment. Among patients receiving corticosteroids at baseline, the mean corticosteroid dose decreased by 3.4 mg/day by Week 24 and by 5.0 mg/day at Week 50, although these analyses involved small numbers of patients.
Safety Findings
Treatment-related adverse events occurred in 10 of 22 patients (45%) during Part A and four of 15 patients (27%) during Part B. In Part A, the most common treatment-related adverse events were nausea in three patients (14%) and diarrhoea in two patients (9%).
Four patients in Part A experienced serious adverse events, including influenza, pneumonia, haemolytic anaemia and tenosynovitis. None were considered related to rilzabrutinib.
During Part B, one patient experienced severe anaemia considered related to treatment, while another experienced a serious adverse event involving decreased haemoglobin that was not considered treatment-related. No thromboembolic events, adverse events of special interest, treatment discontinuations because of adverse events, or deaths were reported through the 50-week data cutoff. No atrial fibrillation, bleeding or neutropenia events associated with other BTK inhibitors were reported.
Clinical Significance
The LUMINA 2 findings provide clinical evidence of rilzabrutinib activity in previously treated adults with wAIHA. Overall haemoglobin response occurred in 64% of patients by Week 24, while 80% of patients who entered Part B achieved a durable haemoglobin response. The haemoglobin findings were accompanied by reductions in markers of haemolysis and clinically meaningful improvements in fatigue.
However, the findings should be interpreted in the context of the study design. LUMINA 2 was a small, single-arm, open-label Phase 2b study without a concurrent control group. The results therefore provide evidence of clinical activity but cannot establish comparative efficacy against placebo or another treatment.
The study represents the first reported clinical evaluation of a BTK inhibitor in wAIHA and provides evidence supporting further investigation of rilzabrutinib in this setting.
Reference
Cooper N, Kuter DJ, Frederiksen H, et al. Rilzabrutinib, an oral Bruton tyrosine kinase inhibitor, in patients with warm autoimmune haemolytic anaemia: a prospective, single-arm, multicentre, phase 2b safety and clinical activity study (LUMINA 2). Lancet Haematol. 2026;13:e698-e709. https://doi.org/10.1016/S2352-3026(26)00218-8
Efficacy, Safety and Pharmacokinetics of Rilzabrutinib in Patients With Warm Autoimmune Hemolytic Anemia (wAIHA) (LUMINA 2), ClinicalTrials.gov ID NCT05002777
About the Writer
Anshu Gupta (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, regulatory affairs, and medical writing. She has presented research at academic conferences and completed certifications in Good Clinical Practice (GCP), ICH-GCP, and drug safety. Passionate about clinical trials and evidence-based medicine, she is committed to translating scientific evidence into accurate, reliable, and accessible healthcare content.