Serial treatment of relapsed/refractory multiple myeloma with different BCMA-targeting therapies

Abstract

1. Myeloma patients progressing on BCMA-targeted therapy can maintain BCMA expression and still respond to different BCMA-targeted therapy.

2. These observations suggest this patient population could be included in ongoing BCMA-targeted therapy trials.

Figure 1.

Treatment course and BCMA expression for patients 1 and 2. (A) Serum M-spike and free λ light chain levels for patient 1 are depicted over time, with treatment timepoints depicted by arrows. (B) Bone marrow aspirate cells from patient 1 pretreatment and 28 days post-BCMA CAR T-cell infusion were gated on live myeloma cells (CD45⁻CD38⁺CD19⁻CD56⁺λ⁺) and assessed for BCMA expression (pink histogram) as described in Cohen et al.Fluorescence minus 1 control (blue histogram) is also shown. (C) Biopsy of a focal bone lesion at progression post-GSK2857916 in patient 1 showed sheets of plasma cells (hematoxylin and eosin; top), with persistent BCMA expression by immunohistochemistry (bottom). Magnification ×200. (D) Serum M-spike and IgG levels for patient 2 are depicted over time, with treatment timepoints depicted by arrows. (E) Bone marrow aspirate mononuclear cells from patient 2 pretreatment and 79 days post-BCMA CAR T-cell infusion was assessed for BCMA expression by flow cytometry, gating on live myeloma cells (CD45⁻CD38⁺CD138⁺CD19⁻, pink histograms) or nonplasma cells (CD45⁺CD38⁻CD138⁻, blue histograms). Patient 1 treated on NCT02546167; patient 2 treated on NCT03288493. Cy, cyclophosphamide; Dex, dexamethasone; Flu, fludarabine; GSK′916, GSK285916 (NCT02064387); Len, lenalidomide; Pembro, pembrolizumab; qPCR, quantitative polymerase chain reaction.