Daratumumab After Stem Cell Transplant in Treating Patients With Multiple Myeloma

PRIMARY OBJECTIVE: I. To determine the anti-myeloma activity of single-agent daratumumab post-autologous stem cell transplantation (ASCT) as assessed by progression-free survival at 1 year post ASCT. SECONDARY OBJECTIVES: I. To characterize the extent of minimal residual disease (MRD) pre-/post-consolidation treatment segment and at one year during the maintenance treatment segment. II. To characterize and evaluate toxicities, including type, frequency severity, attribution, and duration (e.g., infections, secondary primary malignancies, peripheral neuropathy). III. To obtain estimates of overall response rate (stringent complete response \[sCR\], complete response \[CR\], very good partial response \[VGPR\], and partial response \[PR\]), response duration, depth of response, clinical benefit response, and overall survival. EXPLORATORY OBJECTIVES: I. Quantify CD38+ cells from the peripheral blood mononuclear cells (PBMC) fraction, including T, natural killer (NK), and monocytic subsets using pre- and on-daratumumab treatment samples by flow cytometry. II. Assess possible changes in CD38+ expression, as well as the co-receptor marker CD31, and possible correlation with response using pre- and on-daratumumab treatment samples by flow cytometry. III. Assess cytokine levels in peripheral blood plasma. IV. Quantify CD38+ cells from the bone marrow CD-138 negative fractions and acellular fractions, including T, NK, and monocyte subsets using pre- and on-daratumumab treatment samples by flow cytometry. V. Assess possible changes in CD38+ expression, as well as the co-receptor marker CD31, and possible correlation with response using pre- and on-daratumumab treatment samples by flow cytometry. VI. Assess cytokine levels in the bone marrow acellular fraction. VII. Investigate CD38 cellular localization in multiple myeloma cells and extracellular vesicles from blood plasma. VIII. Assess messenger ribonucleic acid (mRNA) expression in the PBMC, the bone marrow CD130-negative fraction, the T cell fraction, and multiple myeloma cells. IX. If differences in CD38 expression are found, investigate epigenetic changes in CD38 mRNA expression. OUTLINE: Patients undergo standard of care ASCT with a conditioning regimen of melphalan. Beginning 60-120 days after ASCT, patients receive daratumumab intravenously (IV) every week for 8 weeks, every 2 weeks for 16 weeks, and then every 4 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 18 months.