Contributions
Abstract: P1532
Type: Poster presentation
Session title: Enzymopathies, membranopathies and other anemias
Background
Cold agglutinin disease (CAD) is a rare hemolytic anemia. Sutimlimab, a humanized monoclonal anti-C1s antibody, received approval in the United States following results of the Phase 3 CARDINAL (NCT03347396) trial.
Aims
This post-hoc analysis aimed to describe the characteristics of patients with CAD who received prior off-label rituximab treatment versus rituximab-naïve patients and present the efficacy of sutimlimab in these subgroups, using pooled data from the Phase 3 CARDINAL and CADENZA (NCT03347422) trials.
Methods
CARDINAL was an open-label, single-arm, multicenter study for patients with a recent blood transfusion. CADENZA was a randomized, double-blind, placebo-controlled, multicenter study in patients without a recent blood transfusion. Included patients had a hemoglobin (Hb) level of ≤10 g/dL and were excluded if they received rituximab monotherapy <3 months, or combination therapy <6 months, prior to enrollment. For this analysis, composite efficacy endpoint was response rate; responders received no blood transfusions or prohibited medications from Week 5 to 26, and had an improvement in Hb from baseline of ≥2.0 g/dL (level chosen for post-hoc analysis) or a Hb level of ≥12 g/dL, at an average of Weeks 23, 25, and 26 (treatment assessment timepoint [TAT]). Secondary endpoints included mean change from baseline to TAT in Hb, bilirubin, lactate dehydrogenase (LDH), and FACIT-Fatigue score. Endpoints were analyzed descriptively according to prior rituximab use (previous monotherapy and/or combination therapy).
Results
Overall, 46 patients receiving sutimlimab were included in this analysis (CARDINAL, n=24; CADENZA, n=22) and mean (SD) time between last rituximab intake and sutimlimab treatment start date was 26.4 (24.0) months. At baseline, 54% (n=25) of patients had prior rituximab use; mean number of rituximab courses received prior to trial enrollment was 1.92. Mean (SD) age was 67.8 (9.7) for patients with prior rituximab use and 69.2 (10.4) years for rituximab-naïve patients. Baseline clinical and laboratory characteristics were similar between subgroups, including Hb, bilirubin, LDH, and FACIT-Fatigue score; however, in CADENZA, immunoglobulin M level and cold hemagglutinin titer were greater in the rituximab-naïve subgroup versus the prior rituximab group (Table).
Accounting for differences in blood transfusion inclusion criteria between CARDINAL and CADENZA, in both trials at baseline there were a greater number of blood transfusions in patients with versus without prior rituximab use (Table). CAD disease duration was longer and corticosteroid use was greater in patients with prior rituximab versus those without. In CARDINAL, CAD-related hospitalizations were greater in prior rituximab users (84.6%) versus those with no prior use (45.5%).
The response rate was 60% in patients with prior rituximab use (n=15/25) and 67% in rituximab-naïve patients (n=14/21). Mean (SD) change from baseline to TAT in Hb level was 2.6 (1.8) and 2.7 (1.8) g/dL for patients with versus without prior rituximab use, respectively. Corresponding values for bilirubin were -28.5 (18.9) versus -25.6 (11.9) µmol/L, and for LDH were -183.8 (267.8) versus -58.9 (178.2) U/L. Mean (SD) change in FACIT-Fatigue score was similar in both subgroups (9.9 [13.0] and 9.8 [11.4], respectively).
Conclusion
In this post-hoc analysis, response rates were similar between subgroups of patients with prior off-label rituximab treatment versus rituximab-naïve patients. These results suggest that sutimlimab is effective in patients with CAD, irrespective of prior off-label rituximab use.
Keyword(s): Anemia, Autoimmune hemolytic anemia (AIHA), Monoclonal antibody, Outcome measurement
Abstract: P1532
Type: Poster presentation
Session title: Enzymopathies, membranopathies and other anemias
Background
Cold agglutinin disease (CAD) is a rare hemolytic anemia. Sutimlimab, a humanized monoclonal anti-C1s antibody, received approval in the United States following results of the Phase 3 CARDINAL (NCT03347396) trial.
Aims
This post-hoc analysis aimed to describe the characteristics of patients with CAD who received prior off-label rituximab treatment versus rituximab-naïve patients and present the efficacy of sutimlimab in these subgroups, using pooled data from the Phase 3 CARDINAL and CADENZA (NCT03347422) trials.
Methods
CARDINAL was an open-label, single-arm, multicenter study for patients with a recent blood transfusion. CADENZA was a randomized, double-blind, placebo-controlled, multicenter study in patients without a recent blood transfusion. Included patients had a hemoglobin (Hb) level of ≤10 g/dL and were excluded if they received rituximab monotherapy <3 months, or combination therapy <6 months, prior to enrollment. For this analysis, composite efficacy endpoint was response rate; responders received no blood transfusions or prohibited medications from Week 5 to 26, and had an improvement in Hb from baseline of ≥2.0 g/dL (level chosen for post-hoc analysis) or a Hb level of ≥12 g/dL, at an average of Weeks 23, 25, and 26 (treatment assessment timepoint [TAT]). Secondary endpoints included mean change from baseline to TAT in Hb, bilirubin, lactate dehydrogenase (LDH), and FACIT-Fatigue score. Endpoints were analyzed descriptively according to prior rituximab use (previous monotherapy and/or combination therapy).
Results
Overall, 46 patients receiving sutimlimab were included in this analysis (CARDINAL, n=24; CADENZA, n=22) and mean (SD) time between last rituximab intake and sutimlimab treatment start date was 26.4 (24.0) months. At baseline, 54% (n=25) of patients had prior rituximab use; mean number of rituximab courses received prior to trial enrollment was 1.92. Mean (SD) age was 67.8 (9.7) for patients with prior rituximab use and 69.2 (10.4) years for rituximab-naïve patients. Baseline clinical and laboratory characteristics were similar between subgroups, including Hb, bilirubin, LDH, and FACIT-Fatigue score; however, in CADENZA, immunoglobulin M level and cold hemagglutinin titer were greater in the rituximab-naïve subgroup versus the prior rituximab group (Table).
Accounting for differences in blood transfusion inclusion criteria between CARDINAL and CADENZA, in both trials at baseline there were a greater number of blood transfusions in patients with versus without prior rituximab use (Table). CAD disease duration was longer and corticosteroid use was greater in patients with prior rituximab versus those without. In CARDINAL, CAD-related hospitalizations were greater in prior rituximab users (84.6%) versus those with no prior use (45.5%).
The response rate was 60% in patients with prior rituximab use (n=15/25) and 67% in rituximab-naïve patients (n=14/21). Mean (SD) change from baseline to TAT in Hb level was 2.6 (1.8) and 2.7 (1.8) g/dL for patients with versus without prior rituximab use, respectively. Corresponding values for bilirubin were -28.5 (18.9) versus -25.6 (11.9) µmol/L, and for LDH were -183.8 (267.8) versus -58.9 (178.2) U/L. Mean (SD) change in FACIT-Fatigue score was similar in both subgroups (9.9 [13.0] and 9.8 [11.4], respectively).
Conclusion
In this post-hoc analysis, response rates were similar between subgroups of patients with prior off-label rituximab treatment versus rituximab-naïve patients. These results suggest that sutimlimab is effective in patients with CAD, irrespective of prior off-label rituximab use.
Keyword(s): Anemia, Autoimmune hemolytic anemia (AIHA), Monoclonal antibody, Outcome measurement