Pomalidomide Induced Hypothyroidism in a Multiple Myeloma Patient: A Case Report

Case Report

Ann Hematol Oncol. 2015; 2(8): 1057.

Pomalidomide Induced Hypothyroidism in a Multiple Myeloma Patient: A Case Report

Hamadeh IS¹, Bourdage KL², Davis AC² and Moreb JS²*

¹Department of Pharmacotherapy and Translational Research, University of Florida, USA

²Department of Medicine, Hematology Oncology Division, University of Florida, USA

*Corresponding author: Moreb JS, Department of Medicine, University of Florida, POB 100277, Gainesville, FL 32610- 0278, USA

Received: October 03, 2015; Accepted: November 10, 2015; Published: November 12, 2015


Pomalidomide is a third generation immunomodulatory agent that is currently reserved for the treatment of patients with relapsed/refractory multiple myeloma (MM). Unlike thalidomide and lenalidomide, hypothyroidism has not previously been reported as a side effect of pomalidomide. Herein, we report a case of hypothyroidism that acutely developed while the patient was receiving the 4th cycle of pomalidomide for refractory MM. The main manifestations were bilateral swelling of all extremities, muscle pain, and fatigue with serum creatinine up to 1.4 mg/dL. These clinical issues made us suspect hypothyroidism. Indeed, upon examination, her TSH was up to 173mIU/L. Her pomalidomide was stopped and she was started on replacement thyroid hormonal therapy with quick improvement in her symptoms and acute kidney failure. In conclusion, we report here the first case of pomalidomide induced clinically significant hypothyroidism. Thus, like with thalidomide and lenalidomide, practitioners prescribing pomalidomide should be aware of this complication and screen for it.

Keywords: Pomalidomide; Hypothyroidism; Immunomodulatory agents; Multiple myeloma

Case Presentation

Our patient is a 51 year old female with an unremarkable past medical history who was diagnosed with stage IIA IgG kappa MM back in December of 2007 when she presented with nonspecific complaints of fatigue and hot flashes. She was found to have microcytic anemia with a hemoglobin level of 9.9g/dL. Further work up including serum protein electrophoresis (SPEP) revealed an elevated serum total protein of 10g/dL (reference range: 6-8g/ dL) and an M-spike of 4.8g/dL. Additionally, serum light chain assay showed the following: kappa light chain of 120mg/L (reference range: 3.3-19.4mg/L), lambda light chain of 4.1mg/L (reference range: 5.71- 26.3mg/L), and a kappa to lambda ratio of 29.26 (reference range: 0.26-1.65mg/L). A skeletal survey revealed no lytic lesions, and a bone marrow biopsy indicated a hypocellular bone marrow with 70-80% plasma cells replacing the normal bone marrow cells. Her serum creatinine, calcium and albumin were all within the reference range. Finally, cytogenetic analysis revealed trisomy chromosome 5 and 7, and deletion of chromosome 13q.

The initial treatment consisted of liposomal doxorubicin (30mg/ m2) and weekly bortezomib 1.3mg/m². At this point in time, her thyroid stimulating hormone (TSH) and T3 levels were within reference range, 1.61mIU/L (reference range: 0.27-4.2mIU/L) and 131ng/dL (80-200 ng/dL), respectively. After receiving four cycles of the induction regimen, the patient underwent autologous peripheral blood stem cell transplant. Follow up studies revealed that she achieved partial remission of her disease. She did not receive post transplant maintenance. Two years later, her disease progressed as evidenced by a continuous or steady rise in her MM markers. Subsequently, she was treated with weekly SQ bortezomib 1.3mg/ m2, weekly dexamethasone 40mg, and lenalidomide 15mg D1-21 every 28 days. Dexamethasone was later omitted from the regimen because of insomnia and agitation. Her MM markers continued to improve with this regimen which she tolerated quite well without any complaints. After receiving 9 cycles, lenalidomide was discontinued and the patient was maintained on bortezomib 1.3 mg/m2 SQ (4 weeks on and 2 weeks off). The patient received a total of 18 cycles of bortezomib maintenance with minimal peripheral neuropathy in her feet. However, following completion of cycle 18, the decision to discontinue bortezomib permanently was made since her MM markers were increasing. Eventually, the patient was switched to pomalidomide monotherapy, 2 mg orally for 21 days of each 28 day cycle. She initially responded, however four months into treatment, the patient complained of fatigue, intolerance to cold, weight gain and swelling in her hands and feet. In addition, her serum creatinine increased to 1.41mg/dL. In light of these complaints, pomalidomide was withheld. Further work up revealed a markedly elevated TSH level at 175mIU/L. Hence, the patient was diagnosed with mild myxedema and referred to an endocrinologist, and was subsequently started on levothyroxine (Synthroid®) 75 micrograms per day. Four weeks after discontinuing pomalidomide and initiating treatment with levothyroxine, her TSH level dropped considerably to 9mIU/L. At the same time, all her symptoms and renal failure improved back to her baseline. She is currently responding to treatment with oral cyclophosphamide and dexamethasone without any signs or symptoms of hypothyroidism.


Multiple myeloma (MM) is a hematologic malignancy characterized by clonal expansion of plasma cells in the bone marrow. With an estimated annual incidence rate of about 20,000 new cases, MM ranks second in terms of prevalence where it accounts for approximately 10% [1] of all cases of hematological malignancies (only second to Non-Hodgkin’s lymphoma).

Although MM is an incurable disease, we have witnessed a dramatic improvement in patient survival over the past few decades [2] primarily attributable to a better understanding of the disease pathogenesis coupled with the emergence of novel agents targeting the aberrant pathways involved in its development. The current pharmacotherapies available for the treatment of MM can be broadly classified into five main categories: alkylating agents, steroids, proteasome inhibitors (PIs), immunomodulatory agents (IMiDs) and histone deacetylase inhibitors (HDACs). Pomalidomide, an oral third generation IMiDs, is the latest addition to the armamentarium of therapeutic options for patients with MM. It was granted accelerated FDA approval back in February of 2013 for use as monotherapy or in combination with dexamethasone in patients with relapsed/refractory MM. The approval came about following the encouraging findings from the CC-4047-MM-002 clinical study which recruited 221 patients with relapsed or refractory MM [3,4]. Of note, the CC-4047- MM-007 [5] study is evaluating the clinical efficacy of pomalidomide when added to bortezomib and low dose dexamethasone in previously treated multiple myeloma patients.

Given the fact that pomalidomide is a thalidomide derivative, the drug is potentially teratogenic, and thereby it is available through a restricted distribution program known as “POMALYST Risk Evaluation and Mitigation Strategy (REMS) Program” where only physicians certified with the program are eligible to prescribe it. Furthermore, pomalidomide is known to cause a variety of hematologic and non hematologic toxicities. To our knowledge, there are no prior reports of pomalidomide associated thyroid dysfunction in the medical literature. Herein, we describe the first case of hypothyroidism typified by a rapid clinical syndrome of hypothyroidism and elevation in TSH that, according to the time course and subsequent outcome, is most likely induced by treatment with pomalidomide.

Hypothyroidism is a well-known side effect of several antineoplastic drugs that belong to different pharmacologic classes (Table 1) [6-9]. Of note, drug induced hypothyroidism is sometimes overlooked given its nonspecific manifestations which tend to overlap with the other side effects of antineoplastic drugs and even with some of the manifestations of malignancies. Pomalidomide is the newest agent of the IMiDs family to gain FDA approval for the treatment of MM in the relapsed or refractory setting. Pomalidomide side effect profile encompasses hematologic (neutropenia, anemia and thrombocytopenia) as well as non hematologic toxicities of which fatigue, fever, skin rash, nausea, constipation, and peripheral neuropathy are the most common (i.e. reported in more than 10% of the patients treated with pomalidomide in phase III clinical trials) [3,10-12].

Citation: Hamadeh IS, Bourdage KL, Davis AC and Moreb JS. Pomalidomide Induced Hypothyroidism in a Multiple Myeloma Patient: A Case Report. Ann Hematol Oncol. 2015; 2(8): 1057. ISSN : 2375-7965