Inolimomab in steroid-refractory acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: retrospective analysis and comparison with other interleukin-2 receptor antibodies.
BACKGROUND
The use of monoclonal antibodies against interleukin-2 receptor (IL-2R)-alpha chains could be an effective treatment of acute graft-versus-host disease (GvHD). Experimental model and clinical studies have reported various results.


METHODS
Inolimomab is a murine anti-IL-2R. Eighty-five patients were evaluated retrospectively for the safety and efficacy of inolimomab given for the treatment of steroid-resistant acute GvHD (aGvHD) following allogeneic hematopoietic stem cell transplantation (HSCT). Diseases were immune deficiency, hematological malignancies, or solid tumors. Seventy-six percent of the patients received a myeloablative regimen. The source of HSCT was bone marrow for 45 patients, peripheral blood for 36 patients, and cord blood for 4 patients. Donors were 49 siblings and 36 unrelated. Acute GvHD was diagnosed within a median of 28 days after transplantation (grade II, 26 patients; grade III, 26 patients; grade IV, 33 patients). Inolimomab was administered in the event of steroid-resistant aGvHD with a median dose of 0.468 mg per kg (median period of treatment: 18 days).


RESULTS
Twenty-five complete responses and 29 partial responses (total response rate: 63%) were observed with no side effects. There was no correlation between aGvHD grading and quality of response. Better responses were observed in cutaneous aGvHD. The overall survival probability was 26% (median follow-up: 20 months). Fifty-seven percent of patients died of toxicity related mortality, mostly aGvHD. Response to inolimomab seemed sustained (11% relapse in responders).


CONCLUSIONS
Inolimomab is well-tolerated and effective for severe steroid-resistant aGvHD. The optimum regimen remains to be defined.
Bay
Jacques-Olivier
JO
Unité de transplantation médullaire, Centre Jean Perrin, Clermont-Ferrand, France. Olivier.bay@cjp.fr
Dhédin
Nathalie
N
Goerner
Martin
M
Vannier
Jean-Pierre
JP
Marie-Cardine
Aude
A
Stamatoullas
Aspasia
A
Jouet
Jean-Pierre
JP
Yakoub-Agha
Ibrahim
I
Tabrizi
Reza
R
Faucher
Catherine
C
Diez-Martin
Jose-Luis
JL
Nunez
Gomez
G
Parody
Rocio
R
Milpied
Noël
N
Espérou
Helène
H
Garban
Frédéric
F
Galambrun
Claire
C
Kwiatkovski
Fabrice
F
Darlavoix
Isabelle
I
Zinaï
Amina
A
Fischer
Alain
A
Michallet
Mauricette
M
Vernant
Jean-Paul
JP
D000208:Acute Disease; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007167:Immunotherapy; D007223:Infant; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D012189:Retrospective Studies; D015996:Survival Rate; D014184:Transplantation, Homologous
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D015375:Receptors, Interleukin-2; C079843:inolimomab