Successful treatment with enasidenib, bortezomib, and dexamethasone for the synchronous occurrence of IDH2-positive acut
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LETTER TO THE EDITOR
Successful treatment with enasidenib, bortezomib, and dexamethasone for the synchronous occurrence of IDH2-positive acute myeloid leukemia and multiple myeloma Donald C. Moore 1 & Viera Nelson 2 & Alaa Muslimani 3 Received: 15 July 2020 / Accepted: 23 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Dear Editor, An 80-year-old male status post-prostatectomy for prostate cancer with a history of diabetes, anemia, leukopenia with absolute neutropenia, vitamin B12 deficiency, and weight loss was diagnosed through a bone marrow biopsy (BMB) with synchronous IDH2-positive acute myeloid leukemia (AML) and multiple myeloma (MM). A total of 5 biopsies did not show metastatic carcinoma. Initial BMB showed a hypercellular marrow with dysgranulopoiesis, dysmegakaryopoiesis, AML with monocytic differentiation, and mutated NPM1 (~ 46% blasts and equivalents). By flow cytometry (FC), monocytes express MPO, CD33, CD64, HLA-DR, aberrant CD56(dim), CD4(small subset), and CD14(small subset), but negative for CD34, CD117, CD13, and CD11b. Karyotype and FISH analysis for MDS and AML were normal. By PCR, FLT3 ITD/TKD mutation was negative. Myeloid molecular profile (MMP; NGS with 44 genes) detected pathogenic alterations in the DNMT3A (41% variable allele frequency [VAF]), IDH2 (24% VAF), NPM1 (22% VAF), SRSF2 (4% VAF), TET2 (9% VAF), and NF1 (29%) (of uncertain significance) (Figures 1 and 2). Enasidenib 100 mg daily was initiated to treat IDH2positive AML. The initial BMB also showed intracytoplasmic kappa monotypic plasma cell myeloma (30–40% of the cellular marrow) with high-risk FISH profile. By FC these plasma cells * Donald C. Moore [email protected] 1
Department of Pharmacy, Atrium Health, Levine Cancer Institute, 100 Medical Park Drive, Concord, NC 28025, USA
2
NeoGenomics, Division of Hematopathology, 2110 Rutherford Rd, Carlsbad, CA 92008, USA
3
Department of Hematology/Oncology, Atrium Health, Levine Cancer Institute, 1656 Riverchase Blvd, Rock Hill, SC 29732, USA
were positive for CD56, CD38, CD13, and negative for CD19, CD20, CD117, and CD45. Myeloma FISH panel identified t(4;14) and monosomy 13 (− 13). Kappa free light chains (FLC) and FLC ratio were 1239 mg/dL and 79.47, res pectiv ely. Ser um pro tein e le ctro phor esis an d immunofixation were negative. Whole-body PET scan was negative. Serum creatinine was 2.6 mg/dL without increase in serum calcium. The patient’s renal insufficiency was considered a myeloma-defining event warranting therapy; bortezomib 1.3 mg/m2 and dexamethasone 20 mg weekly (Vd) was initiated for MM. He received 8 months of Vd and then switched to every 2-week bortezomib maintenance. The patient continued the treatment regimen for 16 months with four more bone marrow evaluations. The first follow-up BMB after 3 months of therapy revealed AML with partial response (20–30% blasts). MMP detected the following: DNMT3A (43% VAF), IDH2 (23% VAF), NPM1 (22% VAF), SRSF2 (12% VAF), TET2 (8%, 13% VAF), NF1 (not detected), and NRAS (10% VA
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