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

Abstract

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 multicenter study. First-line treatment included vincristin, adriamycin, and dexamethasone (VAD)-based induction chemotherapy, a cytoreductive autograft (melphalan 200 mg/m(2)) followed by a single dose of nonmyeloablative total body irradiation and allografting from an human leukocyte antigen (HLA)-identical sibling. Primary end points were the overall survival (OS) and event-free survival (EFS) 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-versus-host disease (GVHD) were 38% and 50%, respectively. Complete remission (CR) was achieved in 53% of patients. Profound cytoreduction (CR or very good partial remission) before allografting was associated with achievement of posttransplantation CR (hazard ratio [HR] 2.20, P = .03) and longer EFS (HR 0.33, P < .01). Conversely, development of chronic GVHD was not correlated with CR or response duration. This tandem transplantation 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 pretransplantation cytoreduction and posttransplantation graft-versus-myeloma effects to further improve clinical outcomes. (http://ClinicalTrials.gov; NCT-00702247.).

Trial registration: ClinicalTrials.gov NCT00702247.

Figures

Figure 1

Cumulative incidence estimates of GVHD and mortality. (A) Acute GVHD: grade 2 to 4 GVHD 38% (solid line); grade 4.3% (dotted line). (B) Transplantation-related mortality: 11%. (C) Disease-related mortality: 5.2% at 2 years; 20.5% at 5 years.

Figure 2

Kaplan-Meier estimates of OS and EFS after a follow up of 5 years. OS (A) and EFS (B) by intention-to-treat principle; OS (C) and EFS (D) among patients who completed the program.

Figure 3

Clinical outcome. Standard OS (gray solid line) by Kaplan-Meier, “current progression-free survival” (dotted line) as described by Klein et al (see “Methods”), which includes responses to salvage therapies and standard EFS (black solid line) by Kaplan-Meier.

Figure 4

Clinical outcome. (A) OS between patients without del(13)q (solid line; median not reached) and patients with del(13)q (dotted line; median 4.3 years). (B) EFS between patients without del(13)q (solid line; median 4.3 years) and patients with del(13)q (dotted line; median 2.2 years). P = .01.