European Journal of Cardiovascular Medicine

Thalidomide, an immunomodulatory agent originally introduced as a sedative, was withdrawn from the market due to its teratogenicity (1). In recent decades, it has regained clinical relevance for its efficacy in treating various hematological malignancies, particularly multiple myeloma and certain lymphomas. Its therapeutic benefits are attributed to anti-inflammatory, anti-angiogenic, and immunomodulatory properties (2). Despite these advantages, thalidomide is associated with a range of adverse effects, including neurotoxicity, sedation, constipation, and most notably, thromboembolic complications (3).

While venous thromboembolism (VTE) is a well-documented risk with thalidomide, especially when used in combination with corticosteroids or chemotherapeutic agents, arterial thrombotic events such as acute myocardial infarction (AMI) are considerably rarer and less understood (4). The exact pathophysiological mechanism remains unclear, but is believed to involve endothelial damage, altered cytokine profiles (particularly TNF-α inhibition), increased platelet aggregation, and reduced fibrinolytic activity (5). These effects may be exacerbated in patients with pre-existing cardiovascular risk factors such as diabetes mellitus, hypertension, or dyslipidemia.

Acute coronary syndromes (ACS) in patients receiving thalidomide-based regimens pose diagnostic and therapeutic challenges, as symptoms may overlap with treatment-related fatigue or musculoskeletal pain (6). Moreover, the potential for delayed recognition increases the risk of extensive myocardial damage. Imaging modalities such as Electrocardiography (ECG) and coronary angiography remain essential tools for timely diagnosis, while cessation of the offending agent and initiation of guideline-directed ACS management are crucial for improving clinical outcomes.

Given the rarity of thalidomide-associated AMI, especially in the context of peripheral T-cell lymphoma, this case report highlights the importance of high clinical suspicion and individualized cardiovascular risk assessment before initiating therapy in vulnerable patients.

A 49-year-old man with a medical history of type 2 diabetes mellitus and hypertension was recently diagnosed with peripheral T-cell lymphoma at Tata Memorial Hospital, Mumbai. He was started on a chemotherapy regimen consisting of thalidomide, cyclophosphamide, and prednisolone (TCP regimen) on April 25, 2025. On May 12, 2025, he presented to the emergency department at Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, with a 4-day history of substernal chest pain and progressive shortness of breath. Vital signs were stable on admission. Physical examination revealed no murmurs, rubs, or gallops. There was no peripheral edema.

Figure 1: Electrocardiogram Showing ST-Segment Elevation and Q Waves

Figure 2: Coronary Angiography Demonstrating Thrombotic Occlusions

Figure 3: Histopathology of Inguinal Lymph Node Biopsy

ECG showed ST-segment elevations in leads V2–V6, II, III, and aVF, with Q waves in V3–V6 (Figure 1), consistent with anterior and inferior STEMI. Transthoracic echocardiography revealed severe left ventricular systolic dysfunction. A coronary angiogram revealed a thrombotic total occlusion of the distal LAD and a proximal total occlusion of the PDA (Figure 2).

The left main coronary artery (LMCA) and left circumflex artery (LCX) were angiographically normal. The right coronary artery (RCA) was dominant with slow flow. A lymph node biopsy performed prior to this presentation confirmed the diagnosis of peripheral T-cell lymphoma. Histopathology revealed preserved lymphoid tissue with numerous epithelioid histiocytes, mature plasma cells, and few lymphoid follicles with germinal centers (Figure 3).

Thalidomide was discontinued immediately upon diagnosis of STEMI. The patient was managed according to current ACS guidelines, including dual antiplatelet therapy, high-intensity statin, beta-blockers, and guideline-directed medical therapy for heart failure. He was planned for percutaneous coronary intervention (PCI) to LAD and PDA. The patient showed clinical improvement and was discharged in stable condition on May 20, 2025.

Thromboembolic complications are a well-recognized adverse effect of thalidomide therapy, particularly in patients with hematologic malignancies. While the majority of these events involve VTE, arterial thrombotic events such as AMI are infrequent, with a reported incidence of less than 2% in thalidomide-treated patients (7). The risk appears to be compounded in individuals with pre-existing cardiovascular risk factors such as diabetes mellitus, hypertension, or hyperlipidemia.

The mechanism of thalidomide-associated arterial thrombosis is not fully understood but is believed to involve multiple interrelated pathways. Thalidomide’s inhibition of tumor necrosis factor-alpha (TNF-α) and its immunomodulatory action may promote a prothrombotic state through endothelial injury, increased platelet activation, and reduced fibrinolysis (8, 9). Additional factors such as elevated levels of interleukin-6 (IL-6), increased vascular endothelial growth factor (VEGF), and enhanced thrombin generation may further contribute to vascular events (10). The patient in this case had well-documented risk factors for cardiovascular disease, including long-standing type 2 diabetes and hypertension. He developed symptoms of acute coronary syndrome within 17 days of initiating thalidomide-based chemotherapy. Electrocardiographic and echocardiographic findings confirmed a diagnosis of ST-elevation myocardial infarction (STEMI), and coronary angiography revealed total thrombotic occlusion in both the distal left anterior descending artery (LAD) and proximal posterior descending artery (PDA).

Given the absence of prior ischemic symptoms or known coronary artery disease, the temporal association between thalidomide initiation and the thrombotic event raises suspicion of a drug-induced prothrombotic state. Although spontaneous plaque rupture cannot be excluded, the angiographic appearance of fresh thrombus, without evidence of chronic atherosclerotic burden in the remaining coronary segments, supports a non-atherosclerotic, possibly drug-related etiology. In oncology practice, distinguishing treatment-related vascular events from pre-existing atherosclerotic disease can be challenging, especially when both factors coexist. Risk stratification tools are not routinely applied in this setting, and baseline cardiovascular workup prior to initiating thalidomide or similar agents is often overlooked. Furthermore, prophylactic anticoagulation or antiplatelet therapy, which may be protective in select high-risk patients, remains underutilized due to bleeding concerns and lack of standardized guidelines.

Importantly, this case emphasizes the need for high clinical suspicion and timely intervention. The patient's symptoms were appropriately recognized as ischemic, leading to early ECG, cardiac biomarker evaluation, and angiography. Prompt cessation of thalidomide, initiation of ACS guideline-based treatment, and supportive care led to successful stabilization. Despite this, the case also reflects missed opportunities. There was no documented baseline cardiovascular risk assessment prior to chemotherapy initiation, nor were any prophylactic measures considered, despite the presence of multiple risk factors. A pre-treatment cardiovascular screening protocol—comprising clinical assessment, ECG, and possibly non-invasive imaging—could have better informed therapeutic decisions and potentially mitigated risk.

Recognizing thalidomide-associated myocardial infarction is vital, especially in patients with pre-existing cardiovascular risk factors. In hindsight, a more thorough pre-treatment cardiovascular evaluation may have helped anticipate this complication. While imaging confirms the event, proactive risk assessment and monitoring are essential before initiating thalidomide therapy.

1. Vargesson N, Stephens T. Thalidomide: history, withdrawal, renaissance, and safety concerns. Expert Opin Drug Saf. 2021;20(12):1455–7.
2. Kotb AR, Bakhotmah DA, Abdallah AE, Elkady H, Taghour MS, Eissa IH, et al. Design, synthesis, and biological evaluation of novel bioactive thalidomide analogs as anticancer immunomodulatory agents. RSC Adv. 2022;12(52):33525–39.
3. Islam B, Lustberg M, Staff NP, Kolb N, Alberti P, Argyriou AA. Vinca alkaloids, thalidomide and eribulin‐induced peripheral neurotoxicity: from pathogenesis to treatment. J Peripher Nerv Syst. 2019;24(S2):S63–73.
4. Calafiore V, Giamporcaro S, Conticello C, Romano A, Parisi M, Giuffrida G, et al. A real-life survey of venous thromboembolic events occurring in myeloma patients treated in third line with second-generation novel agents. J Clin Med. 2020;9(9):2876.
5. Campia U. Vascular effects of cancer treatments. Vasc Med. 2020;25(3):226–34.
6. Pandey S, Bradley L, Del Fabbro E. Updates in cancer cachexia: clinical management and pharmacologic interventions. Cancers (Basel). 2024;16(9):1696.
7. Palumbo A, Palladino C. Venous and arterial thrombotic risks with thalidomide: evidence and practical guidance. Ther Adv Drug Saf. 2012;3(5):255–66.
8. Papa A, Tursi A, Danese S, Rapaccini G, Gasbarrini A, Papa V. Venous thromboembolism in patients with inflammatory bowel disease: the role of pharmacological therapy and surgery. J Clin Med. 2020;9(7):2115.
9. Rehman W, Arfons LM, Lazarus HM. The rise, fall and subsequent triumph of thalidomide: lessons learned in drug development. Ther Adv Hematol. 2011;2(5):291–308.
10. Gao Y, Ma G, Liu S, Teng Y, Wang Y, Su Y. Thalidomide and multiple myeloma serum synergistically induce a hemostatic imbalance in endothelial cells in vitro. Thromb Res. 2015;135(6):1154–9.