Updated experience with inolimomab as treatment for corticosteroid-refractory acute graft-versus-host disease

Biol Blood Marrow Transplant. 2013 Mar;19(3):435-9. doi: 10.1016/j.bbmt.2012.11.012. Epub 2012 Nov 20.

Abstract

Refractory acute graft-versus-host disease (aGVHD) remains an important cause of mortality after allogeneic stem cell transplantation. No standard therapy exists once steroids fail to obtain a good response. In 2006, our group published a series of patients who received inolimomab, an anti-interleukin-2 receptor monoclonal antibody, as salvage therapy with initial encouraging results. In this update, we analyzed a larger group of patients with prolonged follow-up. Ninety-two consecutive patients were treated with inolimomab at our center between April 1999 and December 2011. Overall response rate was 42% (complete response in 14%) on day +30. Predictors of failure to respond in the multivariate analysis were overall aGVHD grade IV, instauration of inolimomab before day 15 of aGVHD diagnosis, and severe lymphopenia. Patients without gastrointestinal involvement appeared to do better, with a 70% response rate compared with 39% in patients with gastrointestinal involvement (P = .06). However, the 2-year overall survival rate was of 18% for the entire cohort (95% confidence interval, 10% to 26%) and 33% for day 30 responders (95% confidence interval, 25% to 40%) and Acute GVHD was the main cause of death (49%) followed by opportunistic infections (27%). Results of this update show that although inolimomab is a well-tolerated drug with a moderate number of short-term responses, it is associated with long-term survival in only one-third of responding patients. These data highlight the need to investigate new rescue treatments with sustained effect and the importance of reporting long-term outcomes in GVHD studies.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adrenal Cortex Hormones / administration & dosage
  • Adult
  • Aged
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Female
  • Graft vs Host Disease / drug therapy*
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / pathology
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Interleukin-2 / antagonists & inhibitors
  • Interleukin-2 / immunology
  • Lymphopenia / immunology
  • Lymphopenia / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prospective Studies
  • Severity of Illness Index
  • Survival Analysis
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal
  • Immunosuppressive Agents
  • Interleukin-2
  • inolimomab