A US retrospective observational Study of rituximab initial and retreatment in patients with warm autoimmune hemolytic anemia (wAIHA) Free

BackgroundWarm autoimmune hemolytic anemia (wAIHA) is the most prevalent type (60-70%) of autoimmune hemolytic anemia (AIHA) and is characterized by autoantibody-mediated erythrocyte destruction at body temperature. (Jager et al Blood Reviews, 2020) Rituximab is a common treatment with or following corticosteroids and may be repeated upon relapse, yet real-world evidence characterizing outcomes upon retreatment of relapsing patients remains limited.

AimsThis study aimed to: 1) describe initial rituximab treatment outcomes, 2) evaluate durable hemoglobin (Hgb) response, 3) characterize treatment-based relapse and complications related to rituximab infusion 4) analyze efficacy after 2nd course of rituximab.

MethodsAdult patients with newly diagnosed wAIHA utilizing rituximab were identified in US electronic health records (Optum PanTher EHR) for the period 2010 - 2024. Patients with an AIHA diagnosis (ICD9 283.0*, ICD10 D59.1*) and lab values confirmed wAIHA disease: Hgb < 10 g/dL, direct antiglobulin test positive for IgG antibodies, and an abnormal measurement of haptoglobin, lactate dehydrogenase, or indirect bilirubin. Patients with a diagnosis of cold/mixed type AIHA (ICD-10-CM D59.12, D59.13) or a cold agglutinin titer ≥ 64 were excluded. Patients were required to have treatment with oral corticosteroids (OCS) or non-steroidal immunosuppressants (IST) prior to rituximab initiation. Rituximab regimens were classified as standard (4 weekly doses), alternative (2 doses given 2 weeks apart), single infusion, or extended (>4 infusions).

Treatment-based relapses were defined as the use of rescue therapies >30 days after rituximab or the initiation of a new therapy (OCS, IST, or rituximab). Rescue therapies included erythropoiesis-stimulating agents (ESA), intravenous immunoglobulin (IVIG), blood transfusion, plasma exchange, splenectomy and infused corticosteroids (IVCS) not administered with rituximab.

Durable response in Hgb was defined as an increase of ≥ 2 g/dL and ≥10 g/dL, sustained for at least 28 days. Response duration was calculated as first measurement meeting the criteria to first Hgb measurement below the threshold.

Results 403 wAIHA patients were included (median age 63.1 years, 55% female), 48.1% were classified as secondary wAIHA. Median Hgb at treatment initiation was 6.45 g/dL.

Within 6 months of the 1^st course of rituximab, 65% achieved durable response. Among patients treated with a 2^nd course (n=65), 52.4% achieved durable response. Median time to response in the first course was 90 days and increased to 160 days in the second. Among patients achieving response within 6 months, 27.4% of patients required rescue therapies in the first 30 days post index rituximab administration, driven by blood transfusions (19.0%) and IVIG (7.7%).

After the first rituximab course, response was lost in a cumulative total of 33.8% of patients within 6 months and 47.2% within 12 months; after the 2nd course, response was lost by 44.3% and 62.9% within 6 and 12 months respectively.Median time to treatment-based relapse during 1^st course was 91 days from response, decreased to 74 days following response in the 2^nd course, driven largely by the initiation of a new course of OCS or IVCS rescue.

Initial rituximab course was a single infusion or incomplete in 29.3% of patients and was associated with lower rates of durable response at six months compared to patients who received a complete rituximab course, (49.3% and 70.7% respectively).

Complications related to rituximab infusion ranged depending on the type of rituximab course, between 20% (complete standard) and 37% (extended). Among patients receiving an extended course, treatment was associated with infections (13.6%), cardiac arrhythmias (9.7%), and bowel obstruction/perforation (8.7%).

Conclusion:In this real-world evidence study we observed differences in response outcomes comparing the initial and second course of rituximab. During repeat treatment, a lower percentage of patients achieved durable response and the time to response was about 2 months longer, while the time to relapse was about 1 month shorter. Rituximab was administered as a single infusion or incomplete course in approximately 1/3 of patients which was associated with lower rates of durable response. Taken together, these results highlight the potential limitations of repeat treatment with rituximab and support the need for development of novel therapies.