Prognostic significance of lymphocyte patterns in multiple myeloma patients after autologous transplant

Martin Stork, Renata Bezdekova, Romana Kralova,  Viera Sandecka, Zdenek Adam, Marta Krejci, Ivanna Boichuk, Zdenka Knechtova, Lucie Brozova, Sabina Sevcikova, Lucie Rihova, Ludek Pour

Abstract:

Despite the high efficacy of current induction regimens, most multiple myeloma (MM) patients relapse over time. The link between changes in the immune system and the prognosis of the disease is still not entirely clear. Therefore, we analyzed whether the pattern of bone marrow (BM) lymphocytes during routine BM examination after autologous stem cell transplant (ASCT) is related to disease prognosis or MRD negative complete remission. From 2009 to 2018, 98 MM patients underwent routine BM testing after the first ASCT. Using multi-parametric flow cytometry, twelve BM lymphocyte subtypes were analyzed. In 60% of patients who achieved a complete response (CR), MRD by flow cytometric analysis (sensitivity threshold 10-6) was evaluated. We found an association of relative proportion of BM lymphocyte subtypes with treatment response, progression-free survival (PFS), overall survival (OS), and minimal residual disease (MRD) negativity. Higher relative proportion of memory B cells was associated with inferior median PFS [HR 1.089 (95% CI: 1.023–1.160), p=0.008] and median OS [HR 1.170 (95% CI: 1.074–1.274), p<0.001]. In non-responding patients (minimal response and worse), higher proportion of memory B cells was found when compared to patients achieving CR [3.8% (range 0.5–35.0) vs. 1.0% (range 0.1–12.5); p=0.001]. No significant association of BM lymphocyte subtypes proportion with MRD negative CR was found. Our results show that changes in BM lymphocyte subsets including memory B cells may have prognostic value in MM patients after ASCT.