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Minimal residual disease negativity in multiple myeloma is associated with intestinal microbiota composition

Matthew J. Pianko, Sean M. Devlin, Eric R. Littmann, Aisara Chansakul, Donna Mastey, Meghan Salcedo, Emily Fontana, Lilan Ling, Elizabet Tavitian, John B. Slingerland, Ann E. Slingerland, Annelie Clurman, Antonio L. C. Gomes, Ying Taur, Eric G. Pamer, Jonathan U. Peled, Marcel R. M. van den Brink, Ola Landgren and Alexander M. Lesokhin

Data supplements

Article Figures & Data

Figures

  • Figure 1.

    Fecal microbiota analysis according to MRD status. (A) Linear discriminant analysis (LDA) effect size analysis of microbiota differentially associated with MRD status with subclass of autologous stem cell transplantation (ASCT). (B) Relative abundance of genera Eubacterium and Faecalibacterium by MRD status. (C) Forest plots showing effect of covariates on relative abundance of E hallii and F prausnitzii.

Tables

  • Table 1.

    Baseline characteristics

    All patients (N = 34)MRD(n = 16)MRD+(n = 18)
    Median age, y62.561.565
    Female sex, n (%)13 (38.2)5 (31.3)9 (50)
    Race/ethnicity, n
     White271215
     East Asian211
     African American321
     Unknown/not reported211
    Mean BMI (range), kg/m226.5 (15.5-38.5)28.3 (20.7-38.5)24.9 (15.5-33.2)
    Paraprotein isotype, n
     IgG κ1679
     IgG λ853
     IgA κ303
     IgA λ330
     Light chain κ303
     Nonsecretory110
    Cytogenetic risk, n (%)
     High*10 (29)2 (12.5)8 (44.4)
     Standard24 (69)14 (87.5)10 (55.6)
    ISS stage, n
     I251411
     II615
     III211
     Unknown101
    Induction therapy regimen, n
     KRd + ASCT936
     KRd without ASCT16115
     Other induction + ASCT514
     Other without ASCT413
    Prior ASCT, n (%)14 (41.2)4 (25)10 (55.6)
    Antibiotics within 60 d of stool sample collection, n (%)8 (23.5)2 (12.5)6 (33.3)
    Median serum immunoglobulin (IQR), mg/dL
     IgG584 (480-864)608 (480-1084)584 (488-834)
     IgA69.5 (30.2-109.2)74 (66.5-149)61.5 (26.5-87.5)
     IgM27.8 (14.8-31.5)22.5 (14.2-27.8)24 (17-32.5)
    • Patients with >1 line of therapy and patients on lenalidomide maintenance at time of MRD assessment were excluded.

    • ASCT, autologous stem cell transplantation; BMI, body mass index; Ig, immunoglobulin; ISS, International Staging System; KRd, carfilzomib, lenalidomide, and dexamethasone.

    • * High-risk cytogenetics defined as del(17/17p), t(4;14), t(14;16), t(14;20), gain 1q.

    • Seven patients exposed to trimethoprim/sulfamethoxazole (Bactrim); 1 patient in the MRD+ group exposed to levofloxacin (Levaquin).