tandem melphalan and autolog. sct in mm patients 60 to 70 years of age with and without induction chemotherapy

Conditions: Multiple Myeloma

Summary: patients 60 to 70 years of age with newly diagnosed multiple myeloma were prospectively randomized between 4 cycles of anthracycline/dexamethasone-based induction chemotherapy (a1) or only 2 x 4 days of dexamethasone (a2). a reference arm included patients who could not be randomized (b). tandem melphalan 140 mg/m² (mel140) with autologous transplantation was scheduled for all patients.

in arm a1, patients received 4 cycles of conventional induction therapy with anthracycline/dexamethasone-based regimens. specified in the protocol were vincristine/doxorubicin/dexamethasone (vad), idarubicin/dexamethasone (id) and cyclophosphamide/doxorubicin/dexamethasone (cad). in arm a2, patients were planned to receive only dexamethasone 40 mg orally on days 1-4 and 8-11 for symptom control before stem cell mobilization. for the patients in arm b, a maximum of 6 cycles of induction chemotherapy was allowed. following this, the treatment was identical for all patients. for stem cell mobilization, an age-adjusted iev-regimen with granulocyte-colony stimulating factor (g-csf) was recommended. the target dose for stem cell collection was 6 x 10e+6 cd34 (cluster of differentiation 34)-positive cells/kg (2 transplants and one back-up). the standard dose for each transplantation was 2 x 10e+6 cd34-positive cells/kg. high-dose melphalan at a total dose of 140 mg/m² (mel140) was given in two doses of 70 mg/m² on days -3 and -2. stem cell transplantation (sct) was performed on day 0. a second mel140 course was planned two months after the first. regular bisphosphonate treatment was recommended.

Eligibility criteria:
inclusion criteria: * histological confirmed multiple myeloma stage ii or iii according to the classification of salmon and durie * aged between 60 and 70 years * eastern cooperative oncology group (ecog) performance status 0-2 * signed and dated written informed consent * no previous chemotherapy or not more than one cycle in total or previous chemotherapy of more than one cycle if paused for at least 6 months and not more than six cycles in total (arm a1 and a2 only) * ongoing primary chemotherapy of two to maximum six cycles (arm b only) exclusion criteria: * multiple myeloma stage i according to the classification of salmon and durie without need of any therapy * aged under 60 or over 70 years * ecog performance status \>2 * previous chemotherapy of more than six cycles * informed consent missing * myocardial infarction within the last six months * cardiac dysrhythmia stage iv b according to the classification of lown * heart failure \>nyha ii according to the classification of the new york heart association (nyha), left ventricular ejection fraction \<50% in ecg * severe restrictive or obstructive pulmonary disease (diffusing capacity \<60% under normal) * renal insufficiency including a serum creatinine level \>2mg/dl if not caused by multiple myeloma and reversible * liver diseases combined with an elevation of transaminases and of bilirubin of three times above normal * severe infections (hiv, hepatitis b/c, syphilis etc. ) * severe psychiatric disease * other not curative treated malignant tumor within the last five years * concurrent participation in other clinical studies * other not curative treated malignant tumor within the last five years

Keywords: high-dose chemotherapy autologous blood stem-cell transplantation induction chemotherapy elderly patients