Jason Valent

Myonecrosis in Sickle Cell Anemia—Overlooked and Underdiagnosed

Medical literature detailing muscular complications of sickle cell anemia is sparse and limited to a few case-reports. Features consistent with myositis and myonecrosis are often overlooked and patients are inadequately treated, leading to unforeseen complications. We report an interesting case of sickle cell myonecrosis and review the existing literature on this subject.

Phase I safety data of lenalidomide, bortezomib, dexamethasone, and elotuzumab as induction therapy for newly diagnosed symptomatic multiple myeloma: SWOG S1211.

Phase I safety data of lenalidomide, bortezomib, dexamethasone, and elotuzumab as induction therapy for newly diagnosed symptomatic multiple myeloma: SWOG S1211

Emerging Advances in the Management of Cardiac Amyloidosis

Amyloidosis is a disease in which proteins misfold, aggregate into fibrils, and deposit extracellularly disrupting organ architecture and function. There are two main types which affect the heart: light chain (AL) amyloidosis and transthyretin cardiac amyloidosis (ATTR). There is a misconception that cardiac amyloidosis has no effective treatment options. However, over the past decade, there has been extensive research and drug development. Outcomes are improving in AL amyloidosis with evolving chemotherapeutic regimens and novel monoclonal antibodies. In ATTR, therapies that decrease protein production, prevent dissociation, and promote clearance have the potential to slow or even halt a disease which is uniformly fatal. Selected patients may be candidates for heart and/or stem cell transplant and should be promptly referred to an experienced amyloid program. Herein, we discuss the emerging advances for the treatment of cardiac amyloidosis.

Neuropathy and efficacy of once weekly subcutaneous bortezomib in multiple myeloma and light chain (AL) amyloidosis

Introduction Randomized studies have shown that bortezomib (BTZ) can be given weekly via intravenous (IV) route or twice weekly via subcutaneous (SC) route with lower neuropathy risk and no loss of anti-myeloma efficacy compared to original standard IV twice weekly schedule. Weekly SC should therefore yield the best therapeutic index and is widely used but has not been compared to established administration schedules in the context of a clinical trial. Methods Comprehensive electronic medical record review was done for disease control and neuropathy symptoms of 344 consecutive patients who received their first BTZ-containing regimen for myeloma or AL amyloidosis before or after we changed to SC weekly in December 2010. Univariate and multivariable analyses were carried out that adjusted for age, underlying disease, concurrently used anticancer agents, underlying conditions predisposing to neuropathy, and number of prior regimens compared SC weekly to other schedules. Results Fifty-three patients received BTZ SC weekly, 17 SC twice weekly, 127 IV weekly and 147 IV twice weekly. Risk for neuropathy of any grade was higher with other schedules compared to SC weekly (44.3% vs. 26.9%, p = 0.001) while response rate was similar (72.1% vs. 76.6%, respectively, p = 0.15). Multivariable analyses upheld higher neuropathy risk (Odds ratio 2.45, 95% CI 1.26–4.76, p = 0.008) while the likelihood of not achieving a response (= partial response or better) was comparable (Odds ratio 1.25, 95% CI 0.58–2.71, p = 0.56) for other schedules compared to SC weekly, respectively. Lower neuropathy risk translated into longer treatment duration when BTZ was started SC weekly (p = 0.001). Conclusions Weekly SC BTZ has activity comparable to other schedules and causes low rates of neuropathy.

Solitary extramedullary plasmacytoma of the penis

Solitary extramedullary plasmacytomas are rare plasma cell malignancies, particularly outside the upper aerodigestive tract. A 90-year-old male presented with a penile mass suspicious for penile carcinoma. Pathology revealed the tumor to be an Epstein-Barr virus-associated plasmacytoma with no radiographic evidence of bone or other soft tissue involvement. There was no laboratory evidence of multiple myeloma.

Positive pregnancy tests in a postmenopausal woman due to beta-human chorionic gonadotropin production by multiple myeloma.

Extensive immunochemical characterization has shown that the free beta subunit of hCG (betahCG) can be produced by common epithelial tumors, including lung, colon, and bladder. However, the expression of beta-human chorionic gonadotropin (hCG) in hematologic malignancies and its significance is largely unknown. We present an extremely rare case of positive serum betahCG in a postmenopausal woman with relapsed, refractory multiple myeloma with myeloma cells expressing betahCG on immunohistochemical stain.

Diagnostic challenges in POEMS syndrome presenting with polyneuropathy: A case series

OBJECTIVE To analyze the clinical characteristics of patients with POEMS presenting with polyneuropathy and discuss associated diagnostic challenges. METHOD Retrospective analysis of 6 patients from 2 tertiary-care institutions. RESULTS Six patients presented with progressive sensorimotor deficits predominantly or exclusively in the lower extremities and were diagnosed with POEMS syndrome. In 4 patients, a diagnosis of chronic inflammatory demyelinating polyradiculopathy (CIDP) was mistakenly made. Low concentration of serum paraprotein and elevated vascular endothelial growth factor (VEGF) were detected in all 6 patients. Initial serum immunofixation and skeletal survey were normal in 2 patients each. On nerve conduction studies, motor and sensory responses were absent in the lower extremity in all 6 patients. Conduction velocity slowing and F-wave latency prolongation appear slightly more pronounced than distal motor latency prolongation in the upper extremity. Spinal MRI showed diffuse lumbosacral nerve root enhancement in all. In 3 patients, targeted bone marrow biopsy was needed for confirming the POEMS diagnosis. Treatment with corticosteroids, chemotherapy agent, focal radiation and/or autologous stem cell transplantation led to significant improvement in 5 of 6 patients. CONCLUSION Diagnosis of POEMS should be considered in patients with progressive polyneuropathies of mixed demyelinating and axon loss features, including CIDP patients not responding to standard treatment. A polyradiculoneuropathy rather than a pure polyneuropathy seems to exist in POEMS.

A 70-Year-Old Man With Large Cervical and Mediastinal Lymphadenopathies

We present a case of a 70-year-old man with enlarged mediastinal and cervical lymph nodes that provided interesting radiologic and pathologic observations. The 70-year-old black man was found to have enlarged mediastinal lymph nodes. He had symptoms of atypical chest pain and generalized weakness for 2 weeks prior to the diagnosis. He denied shortness of breath, fever, chills, or night sweats. He was treated for hypertension and onychomycosis. Basic laboratory findings were within normal limits. Pulmonary function tests at the time of presentation showed FEV1, FVC, and FEV1/FVC ratio of 123% predicted, 133% predicted, and 0.7, respectively. Meanwhile, total lung capacity and carbon monoxide diffusing capacity were 103% and 107% predicted, respectively. Two weeks before he presented to our institution, the patient underwent bronchoscopy with transbronchial biopsies of the right lower lobe and endobronchial ultrasound-guided transbronchial needle aspiration of the right hilar lymph nodes.

Phase 1 trial of ibrutinib and carfilzomib combination therapy for relapsed or relapsed and refractory multiple myeloma

Abstract This phase 1, dose-finding study investigated ibrutinib and carfilzomib ± dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma (≥2 lines of therapy including bortezomib and an immunomodulatory agent). Of 43 patients enrolled, 74% were refractory to bortezomib and 23% had high-risk cytogenetics. No dose-limiting toxicities were observed. The recommended phase 2 dose was ibrutinib 840 mg and carfilzomib 36 mg/m2 with dexamethasone. The most common ≥ grade 3 (>10%) treatment-emergent adverse events were hypertension, anemia, pneumonia, fatigue, diarrhea, and thrombocytopenia. Overall response rate was 67% (very good partial response, 21%; stringent complete response, 2%), with an additional 9% minimal response. Median progression-free survival was 7.2 months and was not inferior in refractory nor high-risk patients. Median overall survival was not reached. Ibrutinib plus carfilzomib demonstrated encouraging responses with a manageable safety profile in this advanced population.

Daratumumab proves safe and highly effective in AL amyloidosis

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