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Background: Multiple myeloma is a rare malignancy characterized by the abnormal proliferation of clonal plasma cells often accompanied by an overproduction of monoclonal immunoglobulins. Multiple myeloma primarily affects those of advanced age and the incidence of multiple myeloma below the age of 30 is exceptionally rare. This case presents a rare exception to the norm with a 23 year old patient diagnosed with multiple myeloma.

Case Description: A 23 year old male presented to the emergency department with complaints of back pain, lower extremity weakness, and reduced sensation of the lower extremities. On magnetic resonance imaging, the patient was found to have widespread osseous lesions involving the spine and ribs, pathologic compression fracture at T6, with extraosseous extension of tumor causing cord compression at the level of T6. During admission, the patient underwent T6 corpectomy, laminectomy, and rod placement, with intraoperative biopsies obtained consistent with lambda restricted multiple myeloma. Outpatient follow-up with oncology confirmed the diagnosis of IgA lambda multiple myeloma stage 1 and the patient began treatment with Dara-RVd therapy per the GRIFFIN trial with plans for stem cell transplantation at a future date. The patient responded well to Dara-RVd therapy and further treatment response remains pending at this time

Discussion: Multiple myeloma presenting at the age of 23 is very unusual. In the absence of lab abnormalities (ie. elevated calcium levels, renal insufficiency, anemia, elevated gamma gap) or with lack of acute abnormalities visualized on plain film imaging (as was the case with our patient) the diagnosis of multiple myeloma may be easily missed, especially in younger patients. This case report highlights an atypical presentation of multiple myeloma with the goal that multiple myeloma remain on the list of differential diagnoses despite non-traditional presentations.

Lorlatinib, a relatively new anaplastic lymphoma kinase (ALK) inhibitor, was approved by the United States Food and Drug Administration (FDA) in 2018 for the treatment of non-small cell lung cancer (NSCLC) that is ALK-positive (1). Lorlatinib in particular has been recognized for its ability to cross the blood-brain barrier, making it desirable for patients with metastatic disease of the brain. Among the adverse effects listed by the manufacturer for lorlatinib, the only cardiac event is atrioventricular (AV) block at a rate of 1.9% of patients, with 0.2% developing grade 3 AV block requiring a pacemaker (2). Cardiomyopathy resulting in heart failure secondary to lorlatinib would therefore demonstrate a rare adverse event associated with ALK inhibitors.

A 63 yo male with a complicated past medical history including recurrent stage IV adenocarcinoma of the lung undergoing palliative chemotherapy, with secondary/paraneoplastic dermatomyositis, insulin-managed type 2 diabetes mellitus, dyslipidemia, and Barrett's esophagus presented to the emergency department (ED) with a complaint of worsening shortness of breath and rapid acute respiratory failure that required intubation. History revealed the patient had been experiencing dyspnea since beginning 50 mg daily of lorlatinib as palliative chemotherapy the month prior. Computed tomography angiography (CTA) of the chest demonstrated likely acute pulmonary embolism with large right pleural effusion. Thoracentesis was performed and the patient was intubated and admitted to the ICU. Lab results were concerning for acute kidney injury and hepatic shock, however these improved with fluids and vasopressor support. TTE was performed and the findings were concerning for acute systolic heart failure that cardiology consultation believed to be either stress induced or related to chemotherapy. The patient was tapered off of inotropes and diuresed with IV Lasix, but there was no recovery of LVEF. Ischemic evaluation was performed with a nuclear perfusion stress test. Results of the stress test showed a moderate-sized mild severity partially fixed, partially reversible inferior and inferoapical defect that could be consistent with stress-induced ischemia. The LVEF was measured at 17% with a severely dilated left ventricle. Consultation with cardiology found these findings to be more consistent with nonischemic cardiomyopathy possibly secondary to immunotherapy with lorlatinib. The patient was discharged with a wearable cardioverter defibrillator due to LVEF remaining below 30%.

There is scant documentation in the literature regarding lorlatinib induced cardiomyopathy, but it has been recognized that lorlatinib induced cardiomyopathy is not included in FDA package inserts and may represent a new adverse event (3). From 2016 to 2021, there have been 605 cases of cardiotoxicity associated with all ALK inhibitors when data from the FDA Adverse Event Reporting System (FAERS) were analyzed in a pharmacovigilance analysis (3). These findings highlight the importance of vigilance and understanding of cardiotoxicity associated with ALK inhibitors. Further documentation of similar cases will illustrate the scope of cardiomyopathy associated with lorlatinib. Understanding of serious adverse events associated with ALK inhibitor like lorlatinib will help shape the risk-benefit analysis when choosing appropriate therapy for ALK positive NSCLC.

The microbiota that inhabit the human body have received increasing attention in recent decades. Growing connections have been made between these microbial communities and their confirmed and potential implications in human health and homeostasis. Despite these advancements in understanding, there is still much that is yet to be understood. An area of specific interest is the role these microbiota play in pharmaceutical interventions and conversely how these pharmaceutical interventions affect the overall microbiome of the patient utilizing them. This review serves the purpose of compiling the results of recent research that has tested the effect microbiota have on pharmaceutical interventions and the effect medications have on the human microbiome. Specifically, this review will be focused on medication classes derived from the top twenty-five most prescribed medications in the United States. The drug classes to be examined are: antidepressants, antihypertensives, anxiolytics, antidiabetics, proton pump inhibitors, statins, and thyroid hormone replacement. Results from the studies examined show that microbiota can significantly alter the efficacy of a medication via bacterial metabolism either increasing or decreasing the bioavailability. Research has also shown that medications can alter the composition of the microbiome of the patient, which may contribute to the therapeutic effect or lead to a dysbiosis that is not entirely understood. The growing interest in microbiota-drug interactions may shed light on the variability in patient responses to pharmaceutical therapy and resistance to treatment. This review highlights what is known about these recent developments in drug-microbiota interactions and gaps where more research is needed. Future research into more of these interactions will allow for a potentially more targeted and individualized approach to treatment that may allow for more efficacious treatment of patients.