Description

A man in his 60s, who was diagnosed with IgG kappa multiple myeloma (MM) associated with a 14q32 translocation 8 years ago, is currently undergoing third-line treatment with daratumumab, lenalidomide and dexamethasone (six cycles). He is presenting with worsening anaemia. Bone marrow aspirate confirms the relapse, showing a 50% plasma cell infiltrate (figure 1A). Fluorescence in situ hybridisation detects t(11;14) in 90% of plasma cells (figure 1B, arrows) and a TP53 gene deletion in 10% of plasma cells (figure 1C, arrows).

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Figure 1

Panels (A), (D) and (E) (MGG stain, x100 objective) highlight atypical plasma cells, myeloid blasts and dyserythropoiesis. Panel (B) shows metaphase FISH with MYEOV/CCND1/IGH translocation/dual fusion probe. Panel (C) shows metaphase FISH with TP53/NF1 deletion probe. Panel (F) shows unbalanced t(7;11) translocation associated with t(9;18), loss of chromosomes 11 and 21, a 20q- deletion and marker chromosomes. FISH, fluorescence in situ hybridisation.

After the failure of two treatment regimens (carfilzomib–dexamethasone and bortezomib–venetoclax), a teclistamab regimen was introduced 3 months later. 6 months after achieving remission, the patient presented with pancytopenia and a few circulating blasts. Bone marrow aspirate revealed 40% myeloid blasts (figure 1D), confirmed by flow cytometry, which was positive for CD34, CD123, CD13, CD33 and CD117. Significant dyserythropoiesis was also noted (figure 1E), with no residual plasma cells detected. A complex karyotype was identified, featuring a pseudodiploid clone with 46 chromosomes, including an unbalanced t(7;11) translocation associated with t(9;18), loss of chromosomes 11 and 21, a 20q- deletion, and marker chromosomes (figure 1F). A diagnosis of therapy-related acute myeloid leukaemia (t-AML) was made. After the first cycle of azacitidine and venetoclax, the patient passed away due to infectious complications.

Myelodysplastic syndrome (MDS) and t-AML are becoming increasingly important as secondary malignancies, as advances in MM treatment allow patients to live longer.1 Also, treatment approaches have shifted from extended alkylating therapies to the use of immunomodulatory agents and high-dose therapy with autologous stem cell transplantation.2 However, despite these improvements, the risk of secondary leukaemias remains, and patients who develop these conditions generally face a poor prognosis, as shown in this case. To note, in the advanced stages of bone marrow differentiation, erythroblasts experience a decrease in cell size, loss of their nuclei and degradation of internal organelles prior to migrating through the sinusoidal endothelium. In the context of MDS/AML, significant abnormalities in erythroid maturation within the bone marrow niche may occur, as illustrated here.

This case underscores the ongoing challenges in managing MM, particularly the persistent risk of secondary malignancies such as t-AML despite advancements in therapy.