Melphalan, Prednisone, and Thalidomide or Lenalidomide in Treating Patients With Newly Diagnosed Multiple Myeloma

Inclusion Criteria:

Patients must have a confirmed diagnosis of symptomatic myeloma; for the original diagnosis of myeloma patients should have met the following criteria at one point in their disease course:

Bone marrow plasmacytosis with >= 10% plasma cells or sheets of plasma cells or biopsy proven plasmacytoma

Patient must have had symptomatic disease at initial diagnosis that prompted the initiation of therapy as well as evidence of end-organ damage at the time of diagnosis namely; at least one of the following: anemia, hypercalcemia, bone disease (lytic bone lesions or pathologic fracture), or renal dysfunction

NOTE: Patients with asymptomatic smoldering myeloma (serum m protein >= 3 gm/dL or bone marrow plasma cells >= 10% or greater plus no evidence of anemia, hypercalcemia, lytic bone lesions or renal dysfunction) and monoclonal gammopathy of undetermined significance (serum m protein < 3 gm/dL and bone marrow plasma cells < 10% plus no evidence of anemia, hypercalcemia, lytic bone lesions or renal dysfunction) are not eligible

Patients must be > 65 and have declined alternative treatment OR patients who are >= 18 < 65 are eligible if they:

Are not a candidate for autologous stem cell transplantation in the opinion of the treating physician OR
Have declined transplant or other alternative treatment
Eastern Cooperative Oncology Group (ECOG) performance status =< 2

All tests below must be performed within 28 days prior to randomization:

Serum free light chain assay
Kappa free light chain

Lambda free light chain

NOTE: The serum free light chain test is required to be done if the patient does not have measurable disease in the serum or urine; measurable disease in the serum is defined as having a serum M-spike >= 1 g/dL; measurable disease in the urine is defined as having a urine M-spike >= 200 mg/24 hr
NOTE: urine protein electrophoresis (UPEP) (on a 24 hour collection) is required, no substitute method is acceptable; urine must be followed monthly if the baseline urine M-spike is >= 200 mg/24 hr; please note that if both serum and urine m-components are present, both must be followed in order to evaluate response
Hemoglobin > 7 g/dL
Platelet count > 75,000 cells/mm^3
Absolute neutrophil count > 1000 cells/mm^3
Creatinine < 2.5 mg/dL and creatinine clearance (measured or calculated) > 60 mL/min
Total bilirubin =< 1.5 mg/dL
Serum glutamate pyruvate transaminase (SGPT) [alanine aminotransferase (ALT)] and serum glutamic oxaloacetic transaminase (SGOT) [aspartate aminotransferase (AST)] =< 2.5 times the upper limit of normal
Patients must be previously untreated for myeloma, although prior treatment for myeloma with prednisone or dexamethasone for less than 4 weeks total dosing alone or in combination with thalidomide or lenalidomide for less than 2 weeks total dosing is allowable
Patients may be receiving bisphosphonates or growth factors (erythropoietin) for multiple myeloma; although erythropoietin is allowed, it is strongly discouraged due to increased risk of thrombosis when employed alongside thalidomide and/or lenalidomide therapy
Patients must be willing and able to take prophylaxis with either aspirin at 325 mg/day or alternative prophylaxis with either low molecular weight heparin or Coumadin
Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days and again within 24 hours prior to starting cycle 1 of lenalidomide; further, they must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy; a FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure

Patients must not have uncontrolled inter-current illness that would limit compliance with the study including:

Uncontrolled hypertension
Symptomatic congestive heart failure
Unstable angina
Uncontrolled cardiac arrhythmia
Uncontrolled psychiatric illness or social situation
Prior history of Stevens Johnson syndrome
Patients must not have grade 2 or higher peripheral neuropathy
Patients must not have an active, uncontrolled infection
Female patients MUST NOT be pregnant or breastfeeding; the use of these drugs in this patient population is ABSOLUTELY CONTRAINDICATED; for women of childbearing potential, a negative serum pregnancy test is required within 10-14 days prior to randomization; for female patients of childbearing potential a negative serum pregnancy test must be repeated within 24 hours prior to initiation of treatment, weekly for the first 4 weeks of treatment and then every 4 weeks if the patient's periods are regular or every 2 weeks if they are not; women of childbearing potential must be willing to refrain from sexual intercourse or must be willing to employ a dual method of contraception, one of which is highly effective [intrauterine device (IUD), birth control pills, tubal ligation or partner's vasectomy] and another additional method (condom, diaphragm or cervical cap) starting 4 weeks prior to and while taking lenalidomide and thalidomide and for four weeks after discontinuing this therapy; the male partner of a female using a single form of birth control should use a condom regardless of his vasectomy status
Sexually active males must be willing to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking lenalidomide and thalidomide and for 4 weeks after stopping treatment
Patients must not have had a second active malignancy requiring treatment within the last 2 years, with the exceptions of basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix