ABSTRACT
Background: Multiple myeloma (MM) accounts for 1% to 2% of all cancers. Exposure to the pesticide Agent Orange (AO) has been established as a potential risk factor for the development of monoclonal gammopathy of undetermined significance (MGUS) and, subsequently, MM in Vietnam War veterans. Methods: This study explored variation in survival related to AO exposure, transformation from MGUS to MM, and covariates. Vietnam War veterans with MM or MGUS were identified in Veterans Health Administration (VHA) health records data. Cox proportional hazards models analyzed survival as a function of AO, race, ethnicity, body mass index, nicotine dependence, alcohol use disorder, Charlson Comorbidity Index, and treatment. Autologous hematopoietic cell transplantation for MM was defined by procedure codes. Results: In the VHA 16,366 patients were identified: 11,112 patients diagnosed with MGUS and 7261 with MM during fiscal years 2010 to 2015 were identified; 12% (n = 2007) had both diagnoses. No statistically significant difference in the rate of transformation from MGUS to MM in the AO exposed and AO not exposed groups was found. In survival models, AO exposure was associated with slightly lower mortality. Alcohol use disorder, nicotine dependence, older age, and greater comorbidity burden increased mortality risk. Black race, female sex, obesity/overweight, and hematopoietic cell transplantation for patients with MM were protective factors. AO exposure was associated with decreased mortality for both MM/MGUS groups. Transformation increased mortality risk for patients with MGUS and decreased mortality risk for patients with MM. Conclusions: Because AO exposure is a nonmodifiable risk factor, focus should be placed on modifiable risk factors (eg, nicotine dependence, alcohol and drug use disorders, underlying comorbid conditions) as these were associated with worse outcomes. Future studies should examine the correlation of AO exposure, cytogenetics, and clinical outcomes in these veterans to best identify their disease course and optimize their care in the latter part of their life.
ABSTRACT
Pembrolizumab (Keytruda), an anti-PD-1 antibody used in the treatment of several different malignancies has been identified to cause adverse effects pertaining to multiple body systems which include respiratory, gastrointestinal, dermatologic, and endocrine manifestations known as immune-related adverse events (IRAEs). Skin manifestations have been most described in current literature highlighting the most common adverse effects of this agent. However, adverse outcomes involving the oral mucosa have been rarely identified in the PD-1 and PD-L1 inhibitor classes of immunotherapeutic agents. We present a case of a 71-year-old male who was treated with a chemotherapeutic regimen including pembrolizumab for newly diagnosed squamous cell carcinoma of the lung, who later developed ulcerations on his tongue that were consistent with glossitis. Upon determining that this adverse effect may be immune-related, the patient was treated with oral prednisone 40 mg with a 10 mg taper each subsequent week, which resulted in significant improvement in the patient's symptoms following one month of treatment.
ABSTRACT
Cardiac tamponade is a rare manifestation of relapsing extramedullary multiple myeloma and portends poor prognosis. No cases of cardiac tamponade with co-occurring renal obstruction from plasmacytoma have been reported in the literature, making this case a unique presentation of relapsing multiple myeloma. The presence of known malignancy should not limit our differential diagnosis when evaluating patients with signs of cardiac tamponade.
ABSTRACT
Anaplastic thyroid cancer is an extremely aggressive disease, which at diagnosis is presumed to be stage IV, has a one-year survival of <10%, and at present has no definitive therapy. The combination of dabrafenib/trametinib has recently been investigated in cancers with BRAF V600E mutations, such as anaplastic thyroid cancer, melanoma, non-small cell lung cancer, and cholangiocarcinoma, and has shown promise in treating these malignancies. We report a case of a 71-year-old male with anaplastic thyroid carcinoma with a significant tumor burden in the right upper lobe of the lung and severe sequela of his disease. He was found to have a BRAF V600E mutation and had a dramatic response to dabrafenib/trametinib therapy at full dose (dabrafenib 150 mg BID/trametinib 2 mg daily) that was sustained even with dose reductions (dabrafenib 100 mg BID/trametinib 1.5 daily). The dose had to be reduced due to the development of severe side effects (fevers and uveitis). Combination therapy had to be discontinued after two months. Compassionate use of pembrolizumab was then initiated as his tumor had a PDL1 expression level of 90%. After five cycles of pembrolizumab, he had a recurrence of his disease. This case demonstrates the possible benefit of dabrafenib/trametinib combination therapy for some patients with anaplastic thyroid carcinoma who harbor BRAF V600E mutation and highlights some characteristic side effects of targeted therapy with BRAF/MEK inhibition with pyrexia and uveitis.
