An Attenuated Schedule of the Dara-RVd Regimen for the Treatment of Newly Diagnosed Multiple Myeloma Patients Eligible for Autologous Stem Cell Transplantation

Inclusion Criteria

• Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information. Subject is willing and able to comply with study procedures based on the judgement of the investigator
• Age ≥ 18 years at the time of consent
• Measurable MM diagnosed according to the following standard criteria: * Criteria A and B must be met, in addition to C AND/OR D: ** A) Monoclonal plasma cells in bone marrow ≥ 10% and/or presence of biopsy-proven plasmacytoma ** B) Monoclonal protein (M-protein) present in serum and/or urine, defined as serum M-protein of ≥ 1 g/dL (0.5 g/dL for immunoglobulin A [IgA] MM) OR urine M-protein of ≥ 200 mg/24 hours. Subjects lacking an M-protein meeting those criteria must have a serum free light chain assay with an involved light chain ≥ 10 mg/dL (100 mg/L) and an abnormal serum free light chain ratio ** C) MM-related organ dysfunction (1 or more CRAB criteria listed below): *** Calcium elevation in blood (serum calcium 1 mg/dL ≥ upper limit of normal or > 11 mg/dL) *** Renal insufficiency (creatinine clearance < 40 ml/min or serum creatinine > 2 mg/dL) *** Anemia (hemoglobin < 10 g/dL or ≥ 2 g/dL below normal) *** Bone lesions (lytic bone lesions) on x-rays, CT, MRI or PET ** D) Myeloma-related biomarker of malignancy (1 or more should be fulfilled): *** ≥ 60% bone marrow plasmacytosis *** Serum involved / uninvolved free light chain ratio of ≥ 100, provided absolute level of involved light chain is at least 100 mg/L (10 mg/dL) *** More than one focal lesion on MRI ≥ 5 mm in size
• No prior systemic anti-myeloma therapy lasting more than 28 days (generally one cycle). Any prior therapy must be completed a minimum of 14 days before starting study drugs
• Subjects who require radiotherapy (which must be localized in its field size) may be treated during screening, but initiating study therapy should be deferred until the radiotherapy is completed and 14 days have elapsed since the last date of radiotherapy
• Hemoglobin (Hgb) ≥ 8 g/dL (to be obtained within 21 days prior to initiating study treatment). Transfusion to achieve a hemoglobin of greater than or equal to 8 gm/dL is permitted
• Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L (to be obtained within 21 days prior to initiating study treatment); Use of growth factors is permitted to fulfill this criterion, particularly if low ANC is felt to be due to MM by treating clinician. If low ANC is felt to be due to non-MM causes, such as myelodysplasia or other bone marrow disorders unrelated to MM, then subject should not be enrolled on the study
• Platelets ≥ 50 × 10^9/L if < 50% of bone marrow nucleated cells are plasma cells, and ≥ 30 × 10^9/L if ≥ 50% of bone marrow (BM) nucleated cells are plasma cells (to be obtained within 21 days prior to initiating study treatment); Platelet transfusions are permitted to reach entry criteria. If low platelets are felt to be due to non-MM causes, such as myelodysplasia or other bone marrow disorders unrelated to MM, then subject should not be enrolled on the study
• Calculated or measured glomerular filtration rate (GFR) any GFR as long as not currently dialysis-dependent (to be obtained within 21 days prior to initiating study treatment)
• Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to study treatment. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided
• Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 90 days after last dose of lenalidomide or last daratumumab. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device that meets < 1% failure rate for protection from pregnancy in the product label
• Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 90 days after last dose of lenalidomide or six months after last daratumumab, or at least 7 months after the last dose of bortezomib
• Ability to access video-enabled technology to participate in telemedicine visits (if not being see at University of North Carolina [UNC]-Chapel Hill)

Exclusion Criteria

• Active infection requiring systemic therapy or other serious infection within 14 days prior to study treatment
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study)
• Treatment with any investigational drug or prior cancer treatment within 14 days (or 5 ½ lives) prior to study treatment. The subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ grade 1 or baseline prior to initiating study treatment