Background: Multiple myeloma can be distinguished from asymptomatic myeloma and monoclonal gammopathy of uncertain significance thanks to CRAB factors. Objective: To assess role of CRAB factors in prognosis of cases who had multiple myeloma and being treated with novel therapeutic agents in comparison with non-novel agents. Patients and Methods: A comparative cross-sectional study was conducted in the Hematology Unit, Internal Medicine Department, in Zagazig University Hospitals on 100 patients with multiple myeloma.We looked at how the existence of CRAB factors affected the survival rates of individuals with symptomatic myeloma who were receiving novel therapies. Results: Hb, PLT, albumin were higher in Novel Containing Regimen (NCR) group than Non-Novel Containing Regimen (NNCR) group, while creatinine, Bence Jones protein in urine, serum beta-2-microglobulin and calcium were lower in (NCR) group than (NNCR) group. Bone marrow plasma cells after treatment, lytic lesion, anemia, hypercalcemia and renal insufficiency were lower in (NCR) group than (NNCR) group. About 91% of patients had M protein type IGG and 9% had IGA, the mean bone marrow plasma cells was 24.6 ± 4.3, 21% had abnormal cytogenetics, 25% had high risk FISH, 70% had lytic lesions, 17% had EMD at diagnosis, 29% had anemia (decrease of Hb more than 2 g/dl or to equal or less than 10 g/dl), 17% had hypercalcemia ≥11.5 mg/dl, 16% had renal insufficiency (increase of serum creatinine more than 2 g/dl). Conclusion: Overall survival and progression-free survival for myeloma patients treated with new medicines; both significantly improved.