B2M and hypercalcemia disease: As shown in Table 4, the patients with adverse clinical features, such as higher levels of β2-microglobulin (β2M) (≥ 3.5 mg/dL), IgA myeloma subtype, ISS stage > 2, and lower albumin level (≤ 3.5 g/dL) had higher expression of PD-1 checkpoint (p = 0.06, p = 0.01, p = 0.02, and p = 0.05, respectively), while patients with hypercalcemia (≥ 10 mg/dL of calcium) exhibited elevated levels of CTLA-4 on the pooled CD4 T cells and their subpopulations studied (Teff and Treg) (p = 0.02, p = 0.0006, and p = 0.002, respectively).