Please refer to section 10 12. MEASUREMENT OF EFFECT 12.1 Definition of Disease Status Patients’ disease status at each data collection period will be evaluated based on the International Uniform Response Criteria. Until disease progression, all disease classifications are relative to the patient’s disease status prior to autologous transplant (i.e. study entry). At time of disease progression, disease classifications are relative to the patient’s best response since time of study entry. 12.2 Response Categories 12.2.1 Stringent Complete Response (sCR): sCR requires, in addition to CR (defined below), all of the following: • Normal free light chain ratio (FLC). • Absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. 12.2.2 Complete Response (CR): CR requires all of the following: • Absence of the original monoclonal paraprotein in serum and urine by routine electrophoresis and by immunofixation. The presence of new monoclonal bands consistent with oligoclonal immune reconstitution does not exclude CR. • Less than 5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy, if biopsy is performed. DF/HCC Protocol #: 18-280 Protocol Version Date: 10.17.2020 35 • No increase in size or number of lytic bone lesions on radiological investigations (development of a compression fracture does not exclude CR)*. • Disappearance of soft tissue plasmacytomas. *If not clinically indicated, radiographs are not required to document CR. Patients in whom some, but not all, the criteria for CR are fulfilled are classified as partial responses (see below), providing the remaining criteria satisfy the requirements for partial response. This includes patients in whom routine electrophoresis is negative but in whom immunofixation has not been performed. 12.2.3 Very Good Partial Remission (VGPR): VGPR requires, in addition to PR (defined below), all of the following: • Serum or urine paraprotein detectable by immunofixation but not on electrophoresis. OR • Greater than or equal to 90% reduction in serum paraprotein plus urine paraprotein <100 mg/24hrs. • For free light chain only disease, VGPR requires a 90% reduction of involved light chain 12.2.4 Partial Response (PR) PR requires one of the following: • Greater than or equal to 50% reduction in the level of the serum monoclonal paraprotein and reduction in 24 hour urinary monoclonal paraprotein either by greater than or equal to 90% or to <200 mg/24 hours in light chain disease. • If the only measurable non-bone marrow parameter is FLC, greater than or equal to 50% reduction in the difference between involved and uninvolved FLC levels or a 50% decrease in level of involved FLC with 50% decrease in ratio, • If the bone marrow is the only measurable parameter, greater than or equal to 50% reduction in bone marrow plasma cells given that the baseline count was greater or equal to 30%, • Greater than or equal to 50% reduction in the size of soft tissue plasmacytomas if present at baseline (by radiography or clinical examination). 12.2.5 Stable Disease (SD) • Patients who do not meet criteria for sCR, CR, VGPR, partial response or progressive disease (section 3.1.1.2) are considered to have stable disease (SD). 12.2.6 Disease Progression (PD) Progression from CR or sCR requires one or more of the following: • A reappearance of serum monoclonal paraprotein, with a level of at least 0.5 g/dL. • 24-hour urine protein electrophoresis with at least 200 mg paraprotein/24 hours. • Abnormal FLC levels of >10 mg/dl, only in patients without measurable paraprotein in the serum and urine. • At least 10% plasma cells in a bone marrow aspirate or on trephine biopsy. • Definite increase in the size of existing bone lesions or soft tissue plasmacytomas. • Development of new bone lesions or soft tissue plasmacytomas. • Development of hypercalcemia (corrected serum Ca >11.5 mg/dL or >2.8 mmol/L) not attributable to any other cause. 12.2.7 Progressive Disease (PD) For patients not in CR or sCR, progressive disease requires one or more of the following measured from the time of randomization: • >25% increase in the level of the serum monoclonal paraprotein, which must also be an absolute increase of at least 0.5 g/dL. DF/HCC Protocol #: 18-280 Protocol Version Date: 10.17.2020 36 • >25% increase in 24-hour urine protein electrophoresis, which must also be an absolute increase of at least 200 mg/24 hours. • Absolute increase in the difference between involved and uninvolved FLC levels (absolute increase must be >10 mg/dl), only in patients without measurable paraprotein in the serum and urine. • >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy, which must also be an absolute increase of at least 10%. • Definite increase in the size of existing bone lesions or soft tissue plasmacytomas. • Development of new bone lesions or soft tissue plasmacytomas. • Development of a compression fracture does not exclude continued response and may not indicate progression. • Development of hypercalcemia (corrected serum Ca >11.5 mg/dL or >2.8 mmol/L) not attributable to any other cause. 12.2.8 Minimal residual disease assessment Absence of evidence of clonal myeloma population based on multichannel flow cytometry with discrimination of 1:1x104 – 1x105 13. DATA REPORTING / REGULATORY REQUIREMENTS Adverse event lists, guidelines, and instructions for AE reporting can be found in Section 7.0 (Adverse Events: List and Reporting Requirements). 13.1 Data Reporting 13.1.1 Method The Office of Data Quality (ODQ) will collect, manage, and perform quality checks on the data for this study. 13.1.2 Responsibility for Data Submission Investigative sites within DF/HCC or DF/PCC are responsible for submitting data and/or data forms to the Office of Data Quality (ODQ) in accordance with DF/HCC policies. 13.2 Data Safety Monitoring The DF/HCC Data and Safety Monitoring Committee (DSMC) will review and monitor toxicity and accrual data from this study. The committee is composed of medical oncologists, research nurses, pharmacists and biostatisticians with direct experience in cancer clinical research. Information that raises any questions about participant safety will be addressed with the Overall PI and study team. The DSMC will review each protocol up to four times a year with the frequency determined by the outcome of previous reviews. Information to be provided to the committee may include: up-to-date participant accrual; current dose level information; TLT information; all grade 2 or higher unexpected adverse events that have been reported; summary of all deaths occurring within 30 days of intervention for Phase I or II protocols; for gene therapy protocols, summary of all deaths while being treated and during active follow-up; any response information; audit results, and a summary provided by the study team. Other information (e.g.