Blood levels of immune cells predict survival in myeloma patients: Results of an Eastern Cooperative Oncology Group phase 3 trial for newly diagnosed multiple myeloma patients

Previously, it was reported that patients with multiple myeloma (MM) who have higher baseline levels of blood CD4⁺ or CD19⁺ cells have longer survival. This article extends the analysis of immune cell levels and survival in a large cohort (N = 504) of patients with MM entered on Eastern Cooperative Oncology Group (ECOG) phase 3 trial (9486). Newly diagnosed patients with MM received 2 cycles of vincristine, bischloroethylnitrosourea, melphalan, cytoxan, prednisone (VBMCP) and were treated on one of 3 randomized arms: VBMCP with either interferon or high-dose cyclophosphamide, or VBMCP alone. Blood immune cell levels were studied at trial entry (baseline), after 2 cycles of chemotherapy, after 2 years of therapy, and at relapse. Baseline CD3⁺, CD4⁺, CD8⁺, CD19⁺, and CD4⁺ subset cell levels were all positively associated with survival (P = .0087 to P < .0001). A multivariate analysis incorporating CD4⁺ and CD19⁺ cell levels defined 3 separate groups of patients with MM to survival outcome. Higher CD19⁺ blood levels were positively associated with MM-patient survival at entry to the study, at year 2, and at relapse (P < .0001 at all 3 timepoints). Patients with MM had evidence of immune cell reconstitution after 2 years of therapy, but the rate and extent of recovery was greater for CD8⁺, which was greater than CD4⁺, which was greater than CD19⁺. This latter data affirms the positive relationship between the quantitative status of the blood immune system in MM and survival. In addition, the importance of the CD19⁺ blood cells to survival is evident throughout the course of MM. Therapeutic efforts to maintain an intact immune system may be crucial in maximizing chemotherapeutic and/or immunotherapy efforts in this disease.