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

Abstract

IntroductionDespite remarkable recent advances in its treatment, multiple myeloma remains incurable. 1 Allografting is still regarded as the only potential cure on account of its well-documented graft-versusmyeloma effect observed in a subset of patients. [2][3][4][5] However, its use remains controversial especially in newly diagnosed patients.In the late 1990s, the introduction of reduced intensity/ nonmyeloablative conditionings greatly renewed the interest in allografting, in particular for diseases such as myeloma where the transplantation-related mortality (TRM) with conventional transplantation regimens had been unacceptably high. [5][6][7] Combining the cytoreductive effect of a high-dose melphalan-based autograft with the graft-versus-myeloma effects of a nonmyeloablative allograft reduced TRM even in elderly, medically unfit myeloma patients. 8,9 Our recent comparison between autografting and nonmyeloablative allografting showed that the latter resulted in longer overall survival (OS) and event-free survival (EFS) in newly diagnosed patients younger than 65 years. 10 Preliminary reports from other groups have confirmed our findings. 11,12 Here, we report on an extended experience consisting of 100 newly diagnosed myeloma patients enrolled in a prospective clinical trial (http://ClinicalTrial.gov; NCT-00702247) and treated with nonmyeloablative allografts as part of their first-line treatment at 15 Italian Bone Marrow Transplantation Units of the Gruppo Italiano Trapianti di Midollo Osseo (GITMO). Methods Patients and donorsFrom July 1999 to June 2005, 100 newly diagnosed myeloma patients younger than 65 years were enrolled in a prospective multicenter trial. Informed consent was obtained upon enrollment in accordance with the An Inside Blood analysis of this article appears at the front of this issue.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. Inclusion criteria included diagnosis of untreated Durie & Salmon stage IIA to IIIB multiple myeloma or stage I progressed to require therapy; age less than 65 years; Karnofsky performance status greater than 60%; and presence of an human leukocyte antigen (HLA)-identical sibling donor eligible for peripheral blood stem cell (PBSC) donation. Exclusion criteria included prior treatment for myeloma, abnormal cardiac function and chronic respiratory disease defined as systolic ejection fraction less than 35% and carbon monoxide diffusing capacity less than 40% of predicted or need of continuous supplemental oxygen, respectively; serum bilirubins greater than twice normal and alanine amino transferase (ALAT) and/or aspartate amino transferase (ASAT) greater than 4 times normal; poorly controlled hypertension; pregnancy; and seropositivity for HIV. Patients with active nonhematologic malignancies except nonmelanoma skin cancers or who were less than 5 years from the achievement of complete remissi...

Allogeneic hematopoietic SCT in multiple myeloma: long-term results from a single institution

“…Taking into account the importance of the achievement a low tumor mass at the time of transplantation for the success of the allo-RIC, this type of transplant has been usually performed either at sensitive relapse or as part of a tandem approach in the up-front therapy setting. 21,22 It is of note that in the series with longest follow-up, including up-front and relapsed patients, the PFS is about 25% at 5 years and between 16 and 24% at 10 years and the OS about 55% at 5 years and from 30 to 40% at 10 years. 23,24 It is important to consider that this high-risk procedure is usually only offered to patients with the poorest short-term predicted outcome with conventional therapies.…”

Role of Allogeneic Stem Cell Transplantation in Multiple Myeloma

“…The Gruppo Italiano Trapianti di Midollo recently reported their experience with the same tandem approach. 26 One hundred newly diagnosed patients younger than 65 years were enrolled in a prospective multicenter study. A major strength of the study was the strict enrollment of untreated myeloma patients who underwent the same vincristine, doxorubicin, and dexamethasone (VAD)-based induction chemotherapy before the autologous cytoreductive transplant.…”

“…However, in a recent study by the Gruppo Italiano Trapianti di Midollo (GITMO), the development of chronic GvHD did not correlate with the achievement of remission and duration of response. 26 Thus, a graft-versus-myeloma effect may also be distinct from chronic GvHD and associated with subclinical graft-versus-host reactions, especially after a truly nonmyeloablative conditioning regimen. Moreover, further evidence for graft-versus-myeloma effects are the molecular remissions, prelude to possible cure, that are more commonly observed after myeloablative allografting as compared to autografting and that can occur in up to 50% of patients.…”

Allogeneic stem cell transplantation for multiple myeloma: is there a future?

“…Although CR rates increased to 53% after allotransplant, median EFS was only 37 months. 28 The lack of an apparent cure with ongoing late relapses was disappointing in both studies.…”