Autoimmune hemolytic anemia after nivolumab treatment in Hodgkin lymphoma responsive to immunosuppressive treatment. A case report

Abstract

The patients with refractory Hodgkin lymphoma have a poor prognosis. The nivolumab, an IgG4 monoclonal antibody inhibiting the program death 1 pathway has recently demonstrated its efficacy and its safety in patients with heavily pretreated refractory Hodgkin lymphoma. The side effects of this immunotherapy include autoimmune-like syndromes. A 75-year-old woman with no significant comorbidities was treated by nivolumab (3 mg/kg every 2 wk) as a third-line treatment for refractory Hodgkin lymphoma. A clinical response was observed with the first injection of nivolumab, with a reduction in superficial lymph nodes. After the second injection, the patient presented an authentic autoimmune hemolytic anemia with a profound anemia at 64 g/L and biologic characteristics of hemolysis (elevated unconjugated bilirubin, lactate dehydrogenase, and reticulocytes). The direct antiglobulin test was strongly positive for IgG antibodies, and the indirect antiglobulin test became positive with a very high level of autoantibodies. After 2 injections of nivolumab, the patient underwent a fluodeoxyglucose F 18 positron emission tomography-computed tomography, showing a partial response according to modified Cheson criteria. A treatment with prednisone (2 mg/kg), initiated after transfusion of 2 units of red blood cells, permitted the complete resolution of this autoimmune reaction after 3 months of corticotherapy. The fluodeoxyglucose F 18 positron emission tomography-computed tomography performed at the end of the corticotherapy showed a clear disease progression. Considering the very good response achieved after only 2 injections of nivolumab, the limited therapeutic resources for this old woman, and the complete resolution of the autoimmune hemolytic anemia, nivolumab was reintroduced at the same dose, with close clinical and biological monitoring. She received 6 more injections of nivolumab without recurrence of hemolysis.

Autoimmune Hemolytic Anemia as a Complication of Nivolumab Therapy

“…AIHA post-nivolumab therapy appears to be a warm AIHA and is commonly mediated through IgG [3, 5], though IgG and C3 were both positive in one case [4]. Our case was exclusively mediated through C3, and IgG was negative.…”

“…AIHA developed after 8 cycles of nivolumab and responded to short course of steroids. Tardy et al [5] reported a case of AIHA in a patient who received nivolumab in the third line for relapsed Hodgkin's lymphoma. AIHA developed after 2 cycles of nivolumab and responded to prolonged course of steroids (Table 1).…”

“…The anemia occurred after 2 cycles of nivolumab in 2 cases [5], after 5 cycles in one case [3], and after 8 cycles in one case [4]. Thus AIHA associated with nivolumab therapy can occur with nivolumab given in any line, either after initiation of the drug within the first few cycles or later in the clinical course.…”

Autoimmunhämolytische Anämie als Komplikation der Nivolumab-Therapie

“…Bei der AIHA nach einer Nivolumab-Therapie scheint es sich um eine Wärmeantikörper-AIHA zu handeln, die in der Regel durch IgG vermittelt wird [3,5], wobei in einem Fall sowohl der IgG-als auch der C3-Test positiv ausfielen [4]. In unserem Fall war C3 der ausschließliche Mediator; der IgG-Test war negativ.…”

“…In allen berichteten Fällen erhielten die Patienten Nivolumab entweder in der zweiten oder in der dritten Therapielinie. Die Anämie trat in 2 Fällen nach 2 Zyklen Nivolumab auf [5], in einem Fall nach 5 Zyklen [3] und in einem Fall nach 8 Zyklen [4]. Eine Nivolumabassoziiert AIHA kann also in jeder Therapielinie au treten, entwe- …”