Subcutaneous Velcade Plus Oral Melphalan and Prednisone or Plus Cycloposphamide and Prednisone or Plus Prednisone

Inclusion Criteria:

* Age ≥ 75 years old or age \< 75 years with abnormal cardiac, pulmonary, renal or hepatic function (unsuitable for protocol with standard inclusion/exclusion criteria).
* Patient is, in the investigator(s) opinion willing and able to comply with the protocol requirements.
* Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
* Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) during study drug therapy (including dose interruption) and for 4 weeks after discontinuation of Velcade therapy.
* Female patient is either post-menopausal for 24 consecutive months or surgically sterilised or agree to continuous abstinence from heterosexual sexual contact or willing to use two acceptable method of birth control at the same time (one highly effective method and one additional effective method) (Highly Effective Methods: Intrauterine device -IUD-; Hormonal -birth control pills, injections, implants-; tubal ligation; partner's vasectomy; Additional Effective Methods: Latex condom; Diaphragm; Cervical Cap) for 4 weeks prior to beginning study drug therapy, during study drug therapy (including dose interruption) and for 4 weeks after discontinuation of therapy.
* Patient was a newly diagnosed multiple myeloma based on standard criteria
* Patient has measurable disease, defined as follows:
* Secretory myeloma: any quantifiable serum monoclonal protein value (generally, but not necessarily, greater than 1 g/dL of IgG M-Protein and greater than 0.5 g/dL of IgA M-Protein) and, where applicable, urine light-chain excretion of \>200 mg/24 hours;
* Non-secretory myeloma: \> 30% plasma cells in the bone marrow and at least one plasmacytoma \> 2 cm as determined by clinical examination or applicable radiographs (i.e., MRI or CT scan).
* Patient has a Karnofsky performance status \> 50%.
* Patient has a life-expectancy \>3 months
* Pretreatment clinical laboratory values within 14 days of enrolment:
* platelet count ≥ 80x109/L
* hemoglobin ≥ 8 g/dL
* absolute neutrophil count (ANC) ≥ 1.0x109/L
* AST ≤ 2.5 times the upper limit of normal
* ALT ≤ 2.5 times the upper limit of normal
* total bilirubin ≤ 1.5 times the upper limit of normal
* cleareance creatinine ≥ 20 ml/min

Exclusion Criteria:

* Any serious medical condition, laboratory abnormality or psychiatric illness that prevented the subject from signing the informed consent form or placed the subjects at unacceptable risk.
* Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid; \< to the equivalent of dexamethasone 40 mg/day for 4 days).
* Pregnant or lactating females
* Known positive for HIV or active infectious hepatitis type A, B or C
* Peripheral neuropathy or neuropatic pain grade 2 or higher, as defined by National Cancer Institute Common Toxicity Criteria (NCI CTC) 3.0
* Infiltrative pulmonary disease