Reactions Weekly | 2021
Daratumumab/dexamethasone/pomalidomide
Abstract
Myelodysplasia: case report A 71-year-old man developed myelodysplasia during treatment with daratumumab, pomalidomide and dexamethasone for refractory multiple myeloma. The man was hospitalised with rapid worsening of his general condition. He had a 10-year history of refractory multiple myeloma with an immunoglobulin-G (IgG) lambda paraprotein. He had received several unspecified therapeutic lines including two autologous stem cell transplants. Ten months earlier, his treatment was switched to DPD regimen comprising daratumumab, pomalidomide and dexamethasone [dosages and routes not stated] due to increased paraprotein and simultaneous reappearance of hypercalcaemia. Following 2 cycles of the regimen, his paraprotein was undetectable and serum free light chains were normalised. During hospitalisation for his tenth treatment cycle, blood examinations revealed pancytopenia with Hb 79 g/L, WBC count 2.1 × 109/L and platelet count 9 × 109/L. Blood film revealed some hypogranular neutrophils. Treatment-related myelodysplasia was suspected. A bone marrow aspirate revealed hypercellularity with 40% of atypical large cells, eccentric nuclei, fine chromatin, prominent nucleoli and abundant basophilic agranular cytoplasm containing numerous vacuoles. Flow cytometric immunophenotyping revealed high cell mortality, weak CD138+, CD45, very weak CD38 and negativity for CD19, CD20 and CD56. Expression of intracytoplasmic light chain was not detected, consistent with the normal results of serum free light chain studies. Cytogenetic analysis revealed multiple karyotypic abnormalities including numerical and structural abnormalities in an overall hypodiploid karyotype. Molecular analysis detected a tumour protein p53 (TP53) A86Cfs* mutation on sorted CD138+ plasma cells. In the myeloid compartment a protein phosphatase, Mg2+/Mn2+-dependent 1D (PPM1D) E475* and a TP53 R158H mutation were noted. The findings were consistent with therapy-related myelodysplasia [duration of treatments to reaction onset and outcome not stated].