Comparison between antithymocyte globulin and alemtuzumab and the possible impact of KIR-ligand mismatch after dose-reduced conditioning and unrelated stem cell transplantation in patients with multiple myeloma.

Abstract

We compared antithymocyte globulin (ATG) with alemtuzumab in 73 patients with multiple myeloma, who underwent reduced conditioning with melphalan/fludarabine, followed by allogeneic stem cell transplantation from human leucocyte antigen-matched or -mismatched unrelated donors. The ATG group had more prior high-dose chemotherapies (P < 0.001), while bone marrow was used more as the stem cell source in the alemtuzumab group (P < 0.001). Alemtuzumab resulted in faster engraftment of leucocytes (P = 0.03) and platelets (P = 0.02) and in a lower incidence of acute graft versus host disease (GvHD) grades II-IV (24% vs. 47%, P = 0.06). More cytomegalovirus (CMV) seropositive patients in the alemtuzumab group experienced CMV reactivation (100% vs. 47%, P = 0.001). The cumulative incidence of treatment-related mortality at 2 years was 26% [95% confidence interval (CI) = 12-37%] for ATG vs. 28% (95% CI = 15-55%) for alemtuzumab, P = 0.7. There was no significant difference in the estimated 2-year overall and progression-free survival between ATG and alemtuzumab: 54% (95% CI: 39-75%) vs. 45% (95% CI: 28-73%) and 30% (95% CI: 16-55%) vs. 36% (95% CI: 20-62%) respectively. In multivariate analysis, treatment with alemtuzumab had a higher risk for relapse (hazard ratio: 2.37; P = 0.05) while killer immunoglobulin-like receptor (KIR)-ligand mismatch was protective for relapse (P < 0.0001). We conclude that alemtuzumab produced less acute GvHD, but higher probability of relapse. The data implicated a major role of KIR-ligand mismatched transplantation in multiple myeloma.

• Authors: Nicolaus Kröger, Bronwen Shaw, Simona Iacobelli, Tatjana Zabelina, Karl Peggs, Avichai Shimoni, Arnon Nagler, Thomas Binder, Thomas Eiermann, Alejandro Madrigal, Rainer Schwerdtfeger, Michael Kiehl, Herbert Gottfried Sayer, Jörg Beyer, Martin Bornhäuser, Francis Ayuk, Axel Rolf Zander, David I Marks, Clinical Trial Committee of the British Society of Blood and Marrow Transplantation and the German Cooperative Transplant Group
• Journal: British journal of haematology (Br J Haematol) Vol. 129 Issue 5 Pg. 631-43 (Jun 2005) ISSN: 0007-1048 [Print] England
• PMID: 15916686 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antibodies, Neoplasm
• Antilymphocyte Serum
• Antineoplastic Agents
• Receptors, Immunologic
• Receptors, KIR
• Alemtuzumab
• Vidarabine
• fludarabine
• Melphalan

Topics

• Alemtuzumab
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antibodies, Neoplasm (therapeutic use)
• Antilymphocyte Serum (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Disease-Free Survival
• Graft vs Host Disease
• Humans
• Immunophenotyping
• Melphalan (therapeutic use)
• Multiple Myeloma (drug therapy, immunology, surgery)
• Proportional Hazards Models
• Receptors, Immunologic (analysis)
• Receptors, KIR
• Recurrence
• Risk
• Stem Cell Transplantation
• Transplantation Conditioning
• Transplantation, Homologous
• Treatment Outcome
• Vidarabine (analogs & derivatives, therapeutic use)