Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo

Despite recent advances, allografting remains the only potential cure for myeloma. From July 1999 to June 2005, 100 newly diagnosed patients younger than 65 years were enrolled in a prospective multi-center study. First-line treatment included vincristin, adriamycin and dexamethasone (VAD)-based induction chemotherapy, a cytoreductive autograft (melphalan 200 mg/m2) followed by a single dose of non-myeloablative total body irradiation and allografting from an HLA-identical sibling. Primary endpoints were overall (OS) and event-free (EFS) survivals from diagnosis. After a median follow up of 5 years, OS was not reached and EFS was 37 months. Incidences of acute and chronic graft-vs.-host disease (GHVD) were 38% and 50%, respectively. Complete remission (CR) was achieved in 53% of patients. Profound cytoreduction (CR or very good partial remission) prior to allografting was associated with achievement of post-transplant CR (HR 2.20, p=0.03) and longer EFS (HR 0.33, p<0.01). Conversely, development of chronic GVHD was not correlated with CR or response duration. This tandem transplant approach allows prolonged survival and long-term disease control in patients with reduced tumor burden at the time of allografting. We are currently investigating the role of "new drugs" in intensifying pre-transplant cytoreduction and post-transplant graft-vs.-myeloma effects to further improve clinical outcomes.