MINIALO-VELCADE2005: A Phase II National, Open-label, Multicenter, no Controlled Study of Treated With Bortezomib (Velcade) Multiple Myeloma Patients Pre and Post Allogeneic Haematopoietic Progenitor Cell Transplant With no Myeloablative Conditioning
Multiple Myeloma is a plasma cell disorder characterized by an uncontrolled proliferation of
bone marrow plasma cells leading to skeletal destruction with bone pain, anemia, renal
failure, hypercalcemia, recurrent bacterial infections and extramedullary plasmacytomas. It
accounts for 1% of all malignancies and slightly more than 10% of hematologic malignancies,
with an annual incidence of about four per 100.000. Although this disease is incurable with
a median survival of about 3 years, remarkable treatment advances have been recently made,
including high-dose therapy followed by stem cell rescue and, particularly, the introduction
of novel promising agents with new mechanisms of action.
The treatment with alquilant agents, melphalan or cyclophosphamide combined with prednisone
has a median of no more than 3 years survival rate in approximately 50%. The chemotherapy
combination and high-dose dexamethasone increases response rate with minimal effects in
survival benefit. The limited efficacy of conventional treatment produced the introduction
of the high-dose therapy followed by a stem cells transplant in order to increase
antitumoral effect and prolong disease-free overall survival.
This way, autologous stem cells transplant has turned into optimal treatment for patients
younger than 65 years with myeloma. Nevertheless there is increasing evidence that it
benefits only patients who showed complete disease remission after transplantation.
The transcendental factor that determines the CR post-transplantation achievement is the
initial chemotherapy- sensitivity disease, measuring the rapidity and the grade of response
(rapidity of maximum response assessment) and the pre-transplantation M protein level (i.e.,
the grade of response to the initial treatment).
On the other hand, the treatments with alquilant agents can impede the obtention of adequate
numbers of stem cells that make impossible the autotransplantation practice. For this reason
nowadays the treatments based on dexamethasone are used as initial chemotherapy.
However, these regimens and particularly AVD have less activity than alquilant agents
treatment. Bortezomib has shown a fast antimyeloma activity (response after 1 or 2 cycles)
in refractory patients, where myelosuppression and cellular injury are not observed.
Alternating bortezomib and dexamethasone as pre-transplant induction regimen would show the
1. a rapid and high effect raised by means of the use of two drugs with proven activity
when they are administered separately,
2. absence of stem cells injury,
3. different toxicity types avoiding the habitual side effects because of the
dexamethasone abuse, when this one is administered in every cycle as it happens in AVD
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Analyze the efficacy of allogeneic bone marrow transplantation in a reduced-intensity manner combined with bortezomib
Bladé Joan, Dr
HOSPITAL CLÍNIC BARCELONA
Spain: Ministry of Health