Cereblon E3 Ligase Modulators Mezigdomide and Iberdomide in Multiple Myeloma.

Multiple Myeloma (MM) remains a challenging hematological malignancy despite significant advancements made during the past 2 decades. Outcomes have improved by incorporating immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies into treatment algorithms that include high dose chemotherapy and autologous hematopoietic stem cell transplantation. However, many patients may eventually relapse despite these innovations. Newer therapies targeting B-Cell Maturation Antigen (BCMA) offer promise for patients with relapsed or refractory disease. BCMA-targeted therapies carry notable side effects, necessitating vigilant monitoring and proactive infection prevention measures. They can also induce considerable immunosuppression, attributed to lower levels of immunoglobulins and increased susceptibility to infections. There is still a need for alternative treatment options with different mechanisms of action that can be easily administered and have a better safety profile. In addition, pomalidomide only overcomes lenalidomide refractoriness in a subset of patients. This review aims to explore 2 next-generation cereblon E3 ligase modulators (CELMoDs), Mezigdomide (CC92480), and Iberdomide (CC-220). We will discuss the biological aspects of these agents, including their mechanisms of action, efficacy, and toxicity profile, and provide a comprehensive review of current literature. Special attention will be paid to ongoing and future clinical trials that provide insights into the potential of these novel therapies in the management of MM.

Amyloid Light-Chain (AL) Amyloidosis of the Trachea Associated With an Indolent B-cell Neoplasm.

We report the case of a 66-year-old woman who was diagnosed with localized tracheal amyloid light-chain (AL) amyloidosis caused by an underlying B-cell neoplasm. The diagnosis was confirmed through subsequent bronchoscopy and biopsies; however, she experienced a challenging episode of hypoxic respiratory failure that required intervention. Repeat bronchoscopies showed persistent subglottic stenosis and tracheobronchomalacia, which led to tracheal debulking surgery and additional interventions. The patient's treatment began with rituximab, zanubrutinib, and dexamethasone with outpatient follow-up. The rarity of tracheobronchial amyloidosis and its connection to B-cell malignancies are highlighted, emphasizing the challenges in diagnosis and the importance of tailored treatment strategies. The patient's clinical course, characterized by atypical respiratory symptoms, delayed diagnosis, and an evolving treatment approach, underscores the complexities of managing such a rare and intricate case.

Necrotizing Enterocolitis in a Patient With Newly Diagnosed Multiple Myeloma and Hyperviscosity Syndrome: A Case Report.

Multiple myeloma (MM) is a clonal plasma cell proliferative disorder characterized by the abnormal increase of monoclonal paraprotein and can lead to specific end-organ damage. Necrotizing enterocolitis or bowel necrosis is a surgical emergency defined by cellular death because of reduced blood flow to the gastrointestinal tract. We report a case of a 75-year-old female who was diagnosed with hyperviscosity syndrome (HVS) and was sent to ED. Further workup showed that she had a new diagnosis of IgG kappa MM for which she was started on chemotherapy. Later, she developed respiratory distress and abdomen distention with less frequent bowel movements, and general surgery was consulted. CT scan of the abdomen and pelvis with contrast showed findings consistent with bowel ischemia vs infarction. The patient was immediately taken to the operating room, and exploratory laparotomy showed nonsurvivable bowel necrosis. She was transitioned to comfort care and passed away later. We aim to increase awareness among physicians to include HVS as one of the possible complications of MM and to detect it early to prevent morbidity and mortality.

Calciphylaxis in End-Stage Renal Disease: A Rare Condition With High Mortality.

Calciphylaxis is a rare but life-threatening condition, seen in patients with end-stage renal disease (ESRD) on renal replacement therapy. Its pathogenesis is not completely known, but microvascular calcification and thrombosis are considered the likely processes. It is characterized by significant morbidity due to severe pain and nonhealing wounds with frequent hospitalizations. Sepsis is the most common cause of mortality with more than 50% of patients dying within the first year after diagnosis. Optimal management requires a multidisciplinary approach. We describe a case of a 66-year-old female with ESRD on hemodialysis (HD) who presented with severe progressive calciphylaxis wounds on both lower extremities and died within two months after diagnosis. She had multiple admissions in the past for cellulitis when she presented with swelling in the legs and chronic wounds. Our goal is to increase awareness among physicians to include calciphylaxis in their differential diagnosis when treating ESRD patients with significant risk factors to detect it early and prevent morbidity and mortality.

Acute Disseminated Encephalomyelitis (ADEM) After Consecutive Exposures to Mycoplasma and COVID Vaccine: A Case Report.

Acute disseminated encephalomyelitis (ADEM) is an autoimmune demyelinating disease of the central nervous system, commonly triggered by viral infections or after immunization. ADEM occurrences in adults are rare. Full spectrum of complications is unknown for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines. A previously healthy 44-year-old female presented to the emergency room (ER) with acute onset of tingling, numbness, and weakness of both lower extremities, urinary retention, blurred vision in right eye, and midline lower back pain. Physical examination revealed bilateral lower extremity weakness 1/5, absent deep tendon reflexes, and decreased sensation. She received the first dose of SARS-CoV-2 vaccine six days prior to presentation to ER. Imaging of her lumbar spine and head were consistent with an active demyelinating plaque consistent with demyelinating disease either multiple sclerosis (MS) or ADEM. The patient was started on SoluMedrol 500 mg IV twice daily for five days. Serological workup and CSF analysis were nonsignificant except for Mycoplasma pneumonia IgM, elevated myelin basic protein, and positive IgG, IgA, and IgM. Patient gradually improved and was transferred to rehabilitation. Repeat MRI brain and spine showed improvement in previous lesions. However, she had worsening left eye symptoms that prompted her transfer to another facility for plasmapheresis. Plasma exchange was done for five treatments for ADEM. Patient started noticing improvement in vision and was discharged on steroid taper. We report a case of a possible association between ADEM and SARS-CoV-2 mRNA vaccine. It should be considered in the differential diagnosis in any case suggestive of acute demyelination after COVID-19 vaccination.

Cerebral Venous Thrombosis Presenting as a Subacute Headache in a Young Man With Undiagnosed Factor V Leiden Mutation.

Cerebral venous sinus thrombosis (CVT) is a rare but potentially life-threatening condition that presents with non-specific symptoms. This condition is more common in women and can be associated with local infection and hypercoagulable conditions, including protein C and S deficiency, factor V Leiden mutation, anti-thrombin III deficiency, thrombophilia, vasculitis, and malignancy. We report the case of a 24-year-old man who presented with a left temporal headache and right upper and lower extremity paresthesia. He also experienced impaired vision (altered spatial sensation), dental pain, bruxism, nausea, and vomiting. Magnetic resonance imaging and magnetic resonance venography of the brain revealed widespread thrombosis of the cerebral sinuses as well as left superior cerebral cortical veins bilaterally. No evidence of venous infarct was found. Subsequent hematologic evaluation showed the presence of heterozygous factor V Leiden mutation. Testing of family members subsequently revealed the presence of this same mutation in his mother and all three siblings, although there was no family history of stroke, hypercoagulability, or atypical headaches. The patient was started on low-molecular-weight heparin and later transitioned to apixaban. Progression of his headache and visual abnormalities led to the discovery of increased intracranial pressure as demonstrated by papilledema and characteristic findings on computed tomography scan. He was treated with acetazolamide with improvement of his symptoms. CVT is uncommon and can be a diagnostic challenge due to its atypical presentation. Clinicians should consider this diagnosis in patients with a subacute onset of atypical headache, especially when accompanied by seizures, focal neurological deficits, or altered consciousness.