Cold agglutinin disease: Role of rituximab

Cold agglutinin disease is an acquired autoimmune hemolytic anemia, induced by auto-antibodies that, at a cold temperature, bind to the surface of red blood cells and induce lysis. Prevalence is 16 per million inhabitants. This chronic hemolysis of moderate severity affects elderly people and causes anemia, jaundice and acrocyanosis. Symptoms are worsened by exposure to cold temperatures and fever. Diagnosis is made from clinical features, biology, direct Coombs'test and discovery of cold agglutinin in vitro. Rituximab seems to be an efficient treatment with low toxicity, as observed in our case report. Thus, we report the case of one patient successj fully treated with 40 rituximab infusions from June 2001 to December 2008

B06 | PHASE III RANDOMIZED COMMODORE 1 TRIAL: 2-YEAR SAFETY AND EFFICACY OF CROVALIMAB IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA WHO SWITCHED FROM ECULIZUMAB

Crovalimab (crova) is a novel C5 inhibitor (C5i) allowing for maintenance subcutaneous (SC) injection every 4 wks (Q4W). Results from the 24-wk primary treatment period of randomized Phase III COMMODORE 1 trial showed that crova was well tolerated and had similar efficacy in patients (pts) who switched from eculizumab (ecu) to crova vs pts who continued ecu. Here, we report 2-y COMMODORE 1 data. PNH pts receiving ecu for ≥24 wks at study start with LDH ≤1.5×ULN were randomized 1:1 to switch to crova (Arm A) or continue ecu (Arm B) for a 24-wk primary treatment period. After primary treatment, pts in Arm A continued crova, and pts in Arm B switched from ecu to crova if continuing in the extension period (Arm B switch). Long-term efficacy was evaluated up to W97 in the extension period in each arm. Efficacy endpoints were % of pts with hemolysis control (LDH≤1.5×ULN) at each visit from W25-97, % of pts with transfusion avoidance (TA), breakthrough hemolysis (BTH), hemoglobin (hb) stabilization. All 44 pts from Arm A (crova) continued crova and 40/42 pts from Arm B (ecu) switched to crova in the extension period after W25. 42 pts in Arm A and 32 in Arm B switch were receiving crova. Median treatment duration was 106.2 wks. Across Arm A and Arm B switch, 84 pts (173.4 pt years [PY]) were evaluated for the long-term safety of crova. Incidence of adverse events (AEs) per 100 PY was 362.8 for all AEs, 50.8 for treatment-related AEs, 45.6 for Grade ≥3 AEs and 29.4 for serious AEs. The % of fatal AEs was 0.58 per 100 PY; the 1 death was unrelated to treatment. TICRs occurred in 18% of pts (15/84). TICRs signs and symptoms were mainly skin and joint abnormalities (rash and arthralgia) with no renal manifestations, no life-threatening or fatal events and resolved with no change in crova treatment. No meningococcal infections occurred. Mean normalized LDH was maintained at ≤1.5xULN in both arms, with 77-94% of pts in Arm A and 89%-100% in Arm B switch having LDH ≤1.5×ULN at each visit from W25-97. TA was achieved by 76%-84% of pts in Arm A and 75%-81% in Arm B switch; hb stabilization was achieved in 68-73% and 60-70% of pts, respectively. Proportion of pts with a BTH event remained low and generally stable (7-11% in Arm A and 3%-18% in Arm B switch). In COMMODORE 1, crova was well tolerated and disease control was maintained over a 2-y median treatment duration in pts who switched from ecu to crova, showing a durable and consistent efficacy profile