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).
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.
Learning points
Advances in multiple myeloma (MM) therapy increase patient survival but raise the risk of secondary malignancies like therapy-related acute myeloid leukaemia (t-AML).
Treatment for MM has shifted from alkylating agents to immunomodulatory drugs and autologous stem cell transplants, yet secondary leukaemia risk remains.
Myelodysplastic syndrome and t-AML present poor prognoses in MM patients, with significant abnormalities in bone marrow contributing to disease progression.
Footnotes
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Patient consent for publication: Consent obtained directly from patient(s).
Provenance and peer review: Not commissioned; externally peer reviewed.
References
1. Boquoi A, Banahan SM, Mohring A, et al. Therapy-related myeloid neoplasms following treatment for multiple myeloma-a single center analysis. Ann Hematol. 2022;101:1031–8. doi: 10.1007/s00277-022-04775-1.
2. Morton LM, Curtis RE, Linet MS, et al. Trends in risk for therapy-related myelodysplastic syndrome/acute myeloid leukemia after initial chemo/immunotherapy for common and rare lymphoid neoplasms, 2000-2018. EClinMed. 2023;61:102060. doi: 10.1016/j.eclinm.2023.102060.