Obinutuzumab Is a Promising Alternative for the Treatment of Relapsed or Refractory Autoimmune Hematological Disorders

Introduction:

CD20 monoclonal antibodies are utilized in autoimmune hematological disorders to deplete B cells and reduce autoantibody production. Rituximab, a chimeric CD20 monoclonal antibody, has been widely used. However, for patients who are relapsed, refractory or intolerant to Rituximab, Obinutuzumab, a fully humanized CD20 monoclonal antibody, has emerged as a potential alternative. This study evaluates the efficacy and safety of Obinutuzumab in treating immune thrombocytopenic purpura (ITP), immune thrombotic thrombocytopenic purpura (iTTP), and autoimmune hemolytic anemia (AIHA).

Methods:

A retrospective analysis was conducted on a single-center cohort from October 2021 to August 2024. Indications for Obinutuzumab treatment included Rituximab intolerance, relapsed or refractory status following multiple immunosuppressive therapies (including Rituximab), and financial constraints as Obinutuzumab representing a more cost-efficient alternative to the standard Rituximab dosage. Obinutuzumab was administered at 1000 mg on days 1 and 15, with two economically disadvantaged patients receiving a single dose of 1000 mg on day 1. CR for iTTP was defined as a sustained clinical response (platelet count >100×10⁹/L, LDH ≤1.5 times upper normal limit) for at least 30 days post-plasma exchange or achievement of ADAMTS13 remission benchmarks (normal ADAMTS13 activity and negative inhibitor results). For AIHA, CR was defined as a hemoglobin level >100 g/L without transfusion needs. In ITP, CR required a platelet count >100×10⁹/L on two occasions at least 7 days apart without bleeding; partial response (PR) was defined as a platelet count >30×10⁹/L on two occasions with similar criteria.

Results:

As of July 28, 2024, ten patients (three iTTP, two AIHA, five ITP) were included, with a median age of 52 years. All patients had failed steroid treatment and had undergone a median of two additional immunosuppressive therapies, including Rituximab in seven cases. All three iTTP patients achieved and maintained CR within follow-up periods of 14, 11, and 5 months, respectively. Both AIHA patients achieved durable CR at 8 and 9 months of follow-up. Among the ITP cohort, all five patients were on low-dose steroids and received TPO receptor agonists (Eltrombopag, Avatrombopag, Romiplostim) before Obinutuzumab. Responses to Obinutuzumab included three achieving CR and two achieving PR, with sustained responses after a median follow-up of nine months. All five ITP patients tapered or discontinued TPO-RAs, and four of them successfully withdrew steroids. For safety assessment, only one patient experienced an acute infusion reaction (transient hypotension), which resolved with infusion rate adjustment and antihistamines. During a median follow-up of 9 months, three patients developed infections: one pulmonary fungal infection, one related to chronic bronchitis, and one bacteremia, and all recovered with timely antimicrobial treatment.

Conclusion:

Obinutuzumab demonstrates efficacy and safety in managing relapsed or refractory autoimmune hematological disorders, including ITP, iTTP, and AIHA, with potential for sustained responses. For ITP patients, concurrent use of TPO-RAs mitigates bleeding risks, tapering or discontinuation of TPO-RAs may be feasible after the onset of Obinutuzumab's therapeutic effect. Infection was the primary side effect observed, highlighting the need for enhanced prophylaxis.

No relevant conflicts of interest to declare.

Obinutuzumab is a a humanized antineoplastic CD20 antibody used with other chemotherapy drug to treat chronic lymphocytic leukemia or follicular lymphoma in adults.