Rituximab in chronic cold agglutinin disease: a prospective study of 20 patients

Abstract

Chronic cold agglutinin disease (CAD) is an acquired autoimmune hemolytic anemia. Previous therapeutic modalities, including alkylating cytostatics, interferon and prednisolone, have been disappointing. However, several case reports and small-scaled studies have demonstrated promising results after treatment with rituximab. We performed a phase II multicentre trial to investigate the effect of rituximab in CAD, including 20 patients studied from October 2002 until April 2003. Thirteen patients had idiopathic CAD and seven patients had CAD associated with a malignant B-cell lymphoproliferative disease. Rituximab was given in doses of 375 mg/m(2) at days 1, 8, 15 and 22. Sixteen patients were followed up for at least 48 weeks. Four patients were excluded after 8, 16, 23 and 28 weeks for reasons unrelated to CAD. Nine patients (45%) responded to the treatment, one with complete response (CR), and eight with partial response. Eight patients relapsed, one patient was still in remission at the end of follow-up. There were no serious rituximab-related side-effects. Our study confirms previous findings of a favourable effect of rituximab in patients with CAD. However, few patients will obtain CR and, in most patients, the effect will be transient.

Rituximab in the treatment of autoimmune haematological disorders

“…Further investigations are needed to determine whether rituximab maintenance therapy prolongs remission duration in AIHA. In addition to the data reported above showing that patients can respond to re-treatment with rituxumab, preliminary data in small series of AIHA and CAD patients show that durable responses can also be achieved after extended rituximab treatment (Quartier et al, 2001;D'Arena et al, 2006D'Arena et al, , 2007Schöllkopf et al, 2006). In addition, a case report has described a patient with mantle cell lymphoma who developed acquired AIHA that was successfully treated with rituximab …”

“…Responses were observed both in patients with idiopathic AIHA (Quartier et al, 2001;Shanafelt et al, 2003;Zecca et al, 2003;Narat et al, 2005;Berentsen et al, 2006;Schöllkopf et al, 2006;D'Arena et al, 2007) and in those with AIHA secondary to a range of conditions, including bone marrow transplant (Quartier et al, 2001;Zecca et al, 2003), autoimmune disorders (Shanafelt et al, 2003;Zecca et al, 2003), chronic lymphocytic leukaemia (Gupta et al, 2002;Trapè et al, 2003;Zaja et al, 2003b;Narat et al, 2005;D'Arena et al, 2006) and other lymphoproliferative disorders (Trapè et al, 2003;Narat et al, 2005;Schöllkopf et al, 2006). Patients with warm AIHA responded well to rituximab treatment regardless of prior therapy (Quartier et al, 2001;Gupta et al, 2002;Shanafelt et al, 2003;Trapè et al, 2003;Zaja et al, 2003b;Zecca et al, 2003;Narat et al, 2005;D'Arena et al, 2006).…”

“…Rituximab treatment for AIHA was well tolerated and no adverse events were reported for most patients. Adverse events that did occur were predominantly mild to moderate infusionrelated side effects, including hypotension, fever and chills and upper airway oedema (Gupta et al, 2002;Trapè et al, 2003;Zecca et al, 2003;Schöllkopf et al, 2006;Rao et al, 2007). Of the 111 patients for whom safety data were reported, two patients were reported to have experienced grade 4 neutropenia (Gupta et al, 2002;Berentsen et al, 2004), and seven infectious events that were possibly related to rituximab therapy were noted (Quartier et al, 2001;Trapè et al, 2003;Zecca et al, 2003;Narat et al, 2005;Schöllkopf et al, 2006).…”

“…Patients with warm AIHA responded well to rituximab treatment regardless of prior therapy (Quartier et al, 2001;Gupta et al, 2002;Shanafelt et al, 2003;Trapè et al, 2003;Zaja et al, 2003b;Zecca et al, 2003;Narat et al, 2005;D'Arena et al, 2006). Likewise, rituximab was effective in patients with CAD regardless of whether they had previously been treated with immunosuppressant drug regimens and/or corticosteroids (Berentsen et al, 2004;Schöllkopf et al, 2006). In addition, there was no difference between CAD responders and nonresponders with regard to their initial haemoglobin or serum monoclonal antibody levels, cold agglutinin titre or bone marrow j:k ratio (Berentsen et al, 2006).…”

“…An overview of studies employing rituximab in AIHA demonstrated that the speed with which AIHA patients responded to rituximab treatment varied considerably, with some patients responding very quickly and others taking weeks or even months to achieve their maximum response (Gupta et al, 2002;Zaja et al, 2003b;Zecca et al, 2003;Berentsen et al, 2004;Schöllkopf et al, 2006;D'Arena et al, 2007). Responses were observed both in patients with idiopathic AIHA (Quartier et al, 2001;Shanafelt et al, 2003;Zecca et al, 2003;Narat et al, 2005;Berentsen et al, 2006;Schöllkopf et al, 2006;D'Arena et al, 2007) and in those with AIHA secondary to a range of conditions, including bone marrow transplant (Quartier et al, 2001;Zecca et al, 2003), autoimmune disorders (Shanafelt et al, 2003;Zecca et al, 2003), chronic lymphocytic leukaemia (Gupta et al, 2002;Trapè et al, 2003;Zaja et al, 2003b;Narat et al, 2005;D'Arena et al, 2006) and other lymphoproliferative disorders (Trapè et al, 2003;Narat et al, 2005;Schöllkopf et al, 2006).…”