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Case Reports
. 2019 Aug 27;3(16):2487-2490.
doi: 10.1182/bloodadvances.2019000466.

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

Adam D Cohen  1 , Alfred L Garfall  1 , Ahmet Dogan  2 , Simon F Lacey  1 , Chris Martin  3 , Nikoletta Lendvai  2 , Dan T Vogl  1 , Matthew Spear  3 , Alexander M Lesokhin  2   4
Affiliations
Case Reports

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

Adam D Cohen et al. Blood Adv. .

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.

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Conflict of interest statement

Conflict-of-interest disclosure: A.D.C., A.L.G., and S.F.L. have received research support from Novartis and have had intellectual property licensed by the University of Pennsylvania to Novartis. A.D.C. has consulted for GlaxoSmithKline. A.D. has received personal fees from Roche, Corvus Pharmaceuticals, Physicians' Education Resource, Seattle Genetics, Peerview Institute, Oncology Specialty Group, Pharmacyclics, Celgene, and Novartis and research grants from Roche. C.M. and M.S. are employees of Poseida. The remaining authors declare no competing financial interests.

Figures

Figure 1.
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.
See this image and copyright information in PMC

References

    1. Seckinger A, Delgado JA, Moser S, et al. Target expression, generation, preclinical activity, and pharmacokinetics of the BCMA-T cell bispecific antibody EM801 for multiple myeloma treatment. Cancer Cell. 2017;31(3):396-410. - PubMed
    1. Salem DA, Maric I, Yuan CM, et al. Quantification of B-cell maturation antigen, a target for novel chimeric antigen receptor T-cell therapy in myeloma. Leuk Res. 2018;71:106-111. - PMC - PubMed
    1. Trudel S, Lendvai N, Popat R, et al. Targeting B-cell maturation antigen with GSK2857916 antibody-drug conjugate in relapsed or refractory multiple myeloma (BMA117159): a dose escalation and expansion phase 1 trial. Lancet Oncol. 2018;19(12):1641-1653. - PMC - PubMed
    1. Brudno JN, Maric I, Hartman SD, et al. T cells genetically modified to express an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of poor-prognosis relapsed multiple myeloma. J Clin Oncol. 2018;36(22):2267-2280. - PMC - PubMed
    1. Topp MS, Duell J, Zugmaier G, et al. Treatment with AMG 420, an anti-B-cell maturation antigen (BCMA) Bispecific T-Cell Engager (BiTE®) antibody construct, induces minimal residual disease (MRD) negative complete responses in relapsed and/or refractory (R/R) multiple myeloma (MM) patients: results of a first-in-human (FIH) phase I dose escalation study [abstract]. Blood. 2018;132(suppl 1). Abstract 1010.

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