SUTIMLIMAB in PATIENTS with COLD AGGLUTININ DISEASE with PRIOR RITUXIMAB USE VERSUS RITUXIMAB-NAIVE PATIENTS: POST-HOC ANALYSES from PHASE 3 STUDIES.

Roth, A.; Karaouni, A.; Hemim, I.; Msihid, J.; Wang, J.; Wardecki, M.; Yoo, R.; Hill, Q.A.

SUTIMLIMAB in PATIENTS with COLD AGGLUTININ DISEASE with PRIOR RITUXIMAB USE VERSUS RITUXIMAB-NAIVE PATIENTS: POST-HOC ANALYSES from PHASE 3 STUDIES.

All Authors

Roth, A.

Karaouni, A.

Hemim, I.

Msihid, J.

Wang, J.

Wardecki, M.

Yoo, R.

Hill, Q.A.

LTHT Author

Hill, Quentin

LTHT Department

Oncology
Haematology

Publication Date

2024

Item Type

Conference Abstract

Subject

ADULT , AGED , ANAEMIA, HAEMOLYTIC, AUTOIMMUNE , BLOOD TRANSFUSION , CONTROLLED CLINICAL TRIALS AS TOPIC , DOUBLE-BLIND METHOD , DRUG THERAPY , WOMEN , OUTCOME ASSESSMENT , ANAEMIA, HAEMOLYTIC , HOSPITALISATION , ADMINISTRATION, INTRAVENOUS , MEN , MULTICENTRE STUDIES AS TOPIC , DRUG APPROVAL , CLINICAL TRIALS AS TOPIC , RANDOMISED CONTROLLED TRIAL , BILIRUBIN , ADRENAL CORTEX HORMONES , HAEMOGLOBINS , IMMUNOGLOBULINS , PLACEBOS , ANTIBODIES, MONOCLONAL

Abstract

Background: Sutimlimab (SUT) is a humanized monoclonal antibody, inhibiting the classical complement pathway, approved for the treatment of hemolytic anemia in cold agglutinin disease (CAD). Prior to its approval, off-label rituximab was a commonly used treatment for CAD. Aim(s): This post-hoc analysis aimed to describe the characteristics of CAD patients who received prior off-label rituximab treatment vs rituximab-naive patients and assess efficacy of SUT in these subgroups, using pooled data from Phase 3 trials. Method(s): CARDINAL (NCT03347396) was a single-arm, multicenter study in patients with recent blood transfusion (at least one transfusion prior to 6 months of enrollment). CADENZA (NCT03347422) was a randomized, double-blind, placebocontrolled, multicenter study in patients without recent blood transfusion. Patients aged >=18 years, with a confirmed diagnosis of CAD, and hemoglobin (Hb) level of <=10 g/dL were included in both studies. Patients received either intravenous (IV) infusions of SUT or placebo for 6 months in Part A. In CADENZA Part B (safety extension), placebo group initiated SUT while SUT group continued SUT. This study included data from first 6 months of both trials (Part A) and CADENZA Part B extension for the ex-placebo group. Baseline was the last non-missing value prior to receiving SUT. Response rate was defined as: patients who received no blood transfusions or prohibited medications and, had an improvement in Hb of >=2.0 g/dL from baseline, or Hb level of >=12 g/dL at treatment assessment timepoint (TAT). Secondary endpoints included mean change from baseline to TAT in Hb, bilirubin, lactate dehydrogenase (LDH), and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score. Endpoints were analyzed descriptively as per prior rituximab use. Result(s): Overall, 66 patients receiving SUT were included (CARDINAL, n=24; CADENZA SUT arm, n=22; and ex-placebo, n=20). Mean (SD) time between last rituximab dose and SUT treatment start date was 29.3 (23.7) months. At baseline, 58% patients had used rituximab; mean number of rituximab courses received prior to enrollment was 1.66. Mean (SD) age was 67.1 (9.7) years for patients with and 70.5 (9.9) years for patients without prior rituximab use. Baseline characteristics were similar between subgroups, including Hb, bilirubin, LDH, and FACIT-Fatigue score; but, in CADENZA, immunoglobulin M level and cold agglutinin titers were higher in rituximab-naive vs prior rituximab subgroup (Table). Mean (SD) CAD disease duration was longer for patients with (8.5 [7.6] years) vs without (5.3 [5.1] years) prior rituximab use. IV corticosteroid use was greater in patients with prior rituximab use (52.6%) vs those without (25.0%). CAD-related hospitalizations were slightly higher in patients with (34.2%) vs those without (28.6%) prior rituximab use. Response rates were similar in patients with (60.5%) vs without prior rituximab use (60.7%). Mean (SD) change in Hb from baseline to TAT was 2.4 (1.9) g/dL vs 2.6 (1.8) g/dL, bilirubin was-26.5 (17.2) mumol/L vs-22.4 (12.1) mumol/L, and for LDH was-128.9 (260.6) U/L vs-36.4 (184.7) U/L, for patients with vs without prior rituximab use, respectively. Mean (SD) change in FACIT-Fatigue score was similar in both subgroups (8.7 [13.8] vs 9.7 [11.4], respectively). (Table present) Conclusion(s): This post-hoc analysis shows similar response rates, changes in hemolytic markers, and FACIT-Fatigue scores between subgroups of patients treated with SUT with prior rituximab treatment vs rituximab-naive patients. These findings further highlight the efficacy of SUT for CAD patients regardless of their prior off-label rituximab usage.