Partial Response to Small Molecule Inhibition in a Case of Anaplastic Large Cell Lymphoma.

In the era of personalized medicine, small-molecule inhibitors have become key to targeting many malignancies. Multiple hematologic malignancies are driven by small-molecule pathways that are seemingly ripe for such targeting. In this case report, we present a patient who was treated with a mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor for what was originally diagnosed as a histiocytic sarcoma. Re-biopsy ultimately revealed an anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL), but his disease initially showed a remarkable response to MEK inhibition. This case illustrates both the importance of obtaining high-quality biopsy specimens for diagnostic and molecular analysis as well as the need for further research into the molecular drivers of T-cell lymphomas that may be amenable to targeted therapies.

High Thermal Amplitude Red Blood Cell Agglutinating Cold Type Autoantibodies in a Case of Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia and Multiorgan Failure.

A 48-year-old man diagnosed with multiorgan failure and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia developed anemia and polyclonal cold agglutinins that reacted at 37 °C. He recovered after a 2-month hospitalization where he received intensive care support. Cold agglutinins resolved after 2 weeks of supportive care. As red blood cell (RBC) cryptic antigens and warm type autoimmune hemolysis have been recently described in coronavirus disease 2019 (COVID-19) patients, we believe this mechanism may also give rise of clinically detectable cold immunoglobulin M (IgM) autoantibodies. Given the thermal amplitude of this particular agglutinin we believe it is possible that in vivo RBC agglutination could contribute to disease severity.

Randomized Phase II Study of R-CHOP With or Without Bortezomib in Previously Untreated Patients With Non-Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma.

Purpose To evaluate the impact of the addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on outcomes in previously untreated patients with non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Patients and Methods After real-time determination of non-GCB DLBCL using the Hans immunohistochemistry algorithm, 206 patients were randomly assigned (1:1; stratified by International Prognostic Index [IPI] score) to six 21-day cycles of standard R-CHOP alone or R-CHOP plus bortezomib 1.3 mg/m2 intravenously on days 1 and 4 (VR-CHOP). The primary end point, progression-free survival (PFS), was evaluated in 183 patients with centrally confirmed non-GCB DLBCL who received one or more doses of study drug (91 R-CHOP, 92 VR-CHOP). Results After a median follow-up of 34 months, with 25% (R-CHOP) and 18% (VR-CHOP) of patients having had PFS events, the hazard ratio (HR) for PFS was 0.73 (90% CI, 0.43 to 1.24) with VR-CHOP ( P = .611). Two-year PFS rates were 77.6% with R-CHOP and 82.0% with VR-CHOP; they were 65.1% versus 72.4% in patients with high-intermediate/high IPI (HR, 0.67; 90% CI, 0.34 to 1.29), and 90.0% versus 88.9% (HR, 0.85; 90% CI, 0.35 to 2.10) in patients with low/low-intermediate IPI. Overall response rate with R-CHOP and VR-CHOP was 98% and 96%, respectively. The overall survival HR was 0.75 (90% CI, 0.38 to 1.45); 2-year survival rates were 88.4% and 93.0%, respectively. In the safety population (100 R-CHOP and 101 VR-CHOP patients), grade ≥ 3 adverse events included neutropenia (53% v 49%), thrombocytopenia (13% v 29%), anemia (7% v 15%), leukopenia (26% v 25%), and neuropathy (1% v 5%). Conclusion Outcomes for newly diagnosed, prospectively enrolled patients with non-GCB DLBCL were more favorable than expected with R-CHOP and were not significantly improved by adding bortezomib.

Sacituzumab Govitecan, a Novel Antibody--Drug Conjugate, in Patients With Metastatic Platinum-Resistant Urothelial Carcinoma.

Patients with metastatic, platinum-resistant urothelial carcinoma (PRUC) have no Food and Drug Administration-approved therapies. The response rates to second-line chemotherapy have generally been < 20%, with a median overall survival of < 1 year. We report our experience with 6 heavily pretreated patients with advanced PRUC (ClinicalTrials.gov identifier NCT01631552) with the novel antibody-drug conjugate, sacituzumab govitecan (IMMU-132). This antibody-drug conjugate comprises the active metabolite of irinotecan, SN-38, conjugated to an anti-Trop-2 antibody. Trop-2 is widely expressed in ≤ 83% of urothelial carcinomas. Of the 6 patients, 3 had a clinically significant response (progression-free survival, 6.7 to 8.2 months; overall survival, 7.5+ to 11.4+ months). Sacituzumab govitecan was well tolerated. Because of these results, a phase II trial has been initiated. The present report highlights the promise of antibody-drug conjugates, such as sacituzumab govitecan, as a novel therapeutic strategy for the treatment of PRUC.

Refractory Epistaxis due to Severe Factor V Deficiency with Inhibitor.

Factor V deficiency secondary to inhibitors is extremely rare and can be caused by a wide collection of exposures such as bovine thrombin and beta lactamase antibiotics. The management of factor V deficiency with inhibitor is a condition treated based on case reports due to the rarity of this condition. We describe a complicated case of an elderly patient with severe factor V deficiency with high inhibitor titer refractory to FEIBA (anti-inhibitor coagulation complex) treated with NovoSeven concurrently with cyclosporine immunosuppression and Rituxan. Given that there are no consensus guidelines on treatment, this case offers important insight into the therapeutic approaches that can be used to treat such patients.

Severe dermatologic reactions with bendamustine: a case series.

Cutaneous drug reactions make up the largest proportion of adverse events in the medical field. Causality, in particular, is difficult to determine, and therefore, preventing recurrent reactions can be challenging. Bendamustine was initially thought to be a well-tolerated chemotherapy agent with few side effects aside from bone marrow suppression. However, the incidence of cutaneous reactions reported is rising. We describe three such reactions in relation to bendamustine administration in hopes of adding to the awareness of such side effects.

Pheochromocytoma of the urinary bladder: a systematic review of the contemporary literature.

BACKGROUND: Pheochromocytoma (paraganglioma) of the urinary bladder is a rare tumor. Herein we sought to review the contemporary literature on pheochromocytomas of the urinary bladder in order to further illustrate the presentation, treatment options and outcomes of patients diagnosed with these tumors. METHODS: A comprehensive review of the current literature was conducted according to the PRISMA guidelines by accessing the NCBI PubMed database and using the search terms "paraganglioma, pheochromocytoma, bladder." This search resulted in the identification of 186 articles published between January 1980 and April 2012 of which 80 articles were ultimately included in our analysis. RESULTS: Pheochromocytomas usually occurred in young adult Caucasians (mean age, 43.3 years; range,11-84 years). According to the literature, the most common symptoms and signs of pheochromocytomas of the urinary bladder were hypertension, headache, and hematuria. Of the 77 cases that commented on catecholamine production, 65 patients had biochemically functional tumors. Approximately 20% of patients were treated by transurethral resection alone, 70% by partial cystectomy and 10% by radical cystectomy. The 75 patients with follow-up information had a mean follow-up of 35 months. At the time of last follow-up, 15 (14.2%) had disease recurrence, 10 (9.4%) had metastasis, and 65 (61.3%) were alive. CONCLUSIONS: Pheochromocytomas of the urinary bladder tend to be functional and occur mostly in young adult Caucasians. Patients with localized tumors have an extremely favorable prognosis and may be managed by less aggressive modalities, whereas patients with metastatic disease have a significant reduction in survival rates despite aggressive treatment.

Locally advanced paraganglioma of the urinary bladder: a case report.

BACKGROUND: Paraganglioma of the urinary bladder is a rare tumor. Herein we sought to describe a case of locally advanced paraganglioma of the urinary bladder managed by partial cystectomy and extended pelvic lymph node dissection. CASE PRESENTATION: The case of a 43-year old Haitian male with locally advanced paraganglioma of the urinary bladder is presented in detail. Through surgical extirpation, our patient was rendered disease-free. Eighteen months later the patient is doing well without symptoms but is noted to have subcentimeter bilateral pulmonary nodules and retroperitoneal lymph nodes. No further therapy has been initiated at this time. CONCLUSIONS: Patients with localized tumors have an extremely favorable prognosis and may be managed by less aggressive modalities, whereas patients with metastatic disease have a significant reduced survival rate despite aggressive treatment.

A phase 2 multicenter study of tivantinib (ARQ 197) monotherapy in patients with relapsed or refractory germ cell tumors.

BACKGROUND: Tivantinib is a selective, small-molecule inhibitor of the MET receptor tyrosine kinase. Preclinical and phase 1 data suggested a possible role for MET in the pathophysiology of germ cell tumors (GCTs) and a potential clinical benefit from tivantinib in patients with these tumors. METHODS: Men (≥ 16 years) with relapsed or refractory, histologically confirmed, non-central nervous system GCTs received oral tivantinib 360 mg twice daily in 28-day cycles until progressive disease or unacceptable toxicity. The primary endpoint was objective response rate in the first 4 cycles, with study termination for <2 responses among the first 21 patients. Secondary endpoints included 12-week progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Twenty-seven patients were enrolled in 9 months (median age, 32 years). Most patients had tumors with nonseminoma histology (n = 25), and primary tumor sites were testis (n = 24) and mediastinum (n = 3). Among 25 evaluable patients, no objective responses were observed; accrual was halted when the 21st patient became evaluable. Best response was stable disease (n = 5). Median PFS was 1 month, the 12-week PFS rate was 21 %, and median OS was 6 months. Grade 3 or 4 adverse events considered related to study drug included grade 3 pneumonia and grade 3 syncope (n = 1, each). CONCLUSIONS: Tivantinib was well tolerated but did not demonstrate single-agent activity in patients with relapsed/refractory GCTs. Rapid accrual to this phase 2 trial was achieved in this rare patient population through multicenter collaboration.

Safety and efficacy of sorafenib in elderly patients treated in the North American advanced renal cell carcinoma sorafenib expanded access program.

OBJECTIVE: In this retrospective analysis of the Advanced Renal Cell Carcinoma Sorafenib (ARCCS) program in North America, we compared the safety and efficacy of sorafenib in patients aged ≥70 with those aged <70 years. METHODS: Patients were treated with oral sorafenib twice daily until the occurrence of disease progression or treatment intolerance. The primary objective of the ARCCS program was making sorafenib available to patients with advanced renal cell carcinoma (RCC) in the USA and Canada before marketing approval was obtained; the secondary objective was the evaluation of its safety and efficacy. RESULTS: Of the 2,504 patients enrolled in the ARCCS program who received at least 1 dose of sorafenib, 736 (29%) were aged ≥70 years. The most common grade ≥3 adverse events included rash/desquamation (5% in both groups), hand-foot skin reaction (8% in those aged ≥70 years vs. 10% in those <70 years of age), hypertension (5 vs. 4%) and fatigue (7 vs. 4%). Partial response was seen in 4% of the patients in both age groups. The median overall survival for the ≥70-year versus <70-year groups was also similar (46 vs. 50 weeks). CONCLUSIONS: There were no substantial differences in safety and efficacy between patients aged ≥70 and <70 years with advanced RCC treated with sorafenib.

Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America.

BACKGROUND: The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) program made sorafenib available to patients with advanced renal cell carcinoma (RCC) before regulatory approval. METHODS: In this nonrandomized, open-label expanded access program, 2504 patients from the United States and Canada were treated with oral sorafenib 400 mg twice daily. Safety and efficacy were explored overall and in subgroups of patients including those with no prior therapy, nonclear cell (nonclear cell) RCC, brain metastases, prior bevacizumab treatment, and elderly patients. Sorafenib was approved for RCC 6 months after study initiation, at which time patients with no prior therapy or with nonclear cell RCC could enroll in an extension protocol for continued assessment for a period of 6 months. RESULTS: The most common grade > or =2 drug-related adverse events were hand-foot skin reaction (18%), rash (14%), hypertension (12%), and fatigue (11%). In the 1891 patients evaluable for response, complete response was observed in 1 patient, partial response in 67 patients (4%), and stable disease for at least 8 weeks in 1511 patients (80%). Median progression-free survival in the extension population was 36 weeks (95% confidence interval [CI], 33-45 weeks; censorship rate, 56%); median overall survival in the entire population was 50 weeks (95% CI, 46-52 weeks; censorship rate, 63%). The efficacy and safety results were similar across the subgroups. CONCLUSIONS: Sorafenib 400 mg twice daily demonstrated activity and a clinically acceptable toxicity profile in all patient subsets enrolled in the ARCCS expanded access program (clinicaltrials.gov identifier: NCT00111020).

Infusion of palonosetron plus dexamethasone for the prevention of chemotherapy-induced nausea and vomiting.

Serotonin (5-HT3) receptor antagonists are the foundation of standard antiemetic care for cancer patients receiving emetogenic chemotherapy. To enhance the efficacy of these supportive care agents, dexamethasone is routinely admixed with the 5-HT3 receptor antagonist, which is administered by intravenous infusion before chemotherapy begins. This phase II study evaluated the safety and efficacy of intravenous palonosetron admixed with dexamethasone to prevent chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy. Cancer patients received palonosetron 0.25 mg plus dexamethasone 8 mg admixed in 50 mL of infusion solution before receiving at least one qualifying chemotherapeutic agent (cyclophosphamide < or = 1,500 mg/m2, doxorubicin > or = 20 mg/m2, carboplatin, or oxaliplatin). Patients used diaries to record nausea and emesis experienced and rescue medications used. Of 32 participants, 27 (84%) had a complete response (no emesis and no rescue medication) during the acute (0-24 hours) interval posttherapy, 19 (59%) had a complete response during the delayed (> 24-120 hours) posttherapeutic interval, and 19 (59%) had a complete response during the overall (0-120 hours) posttreatment interval. A total of 23 patients (72%) had no emetic episodes, 16 (50%) had no nausea, and 21 (66%) used no rescue medication throughout the overall 5-day interval. The combination was well tolerated. Palonosetron plus dexamethasone given as a pretreatment infusion is effective and safe in preventing acute and delayed CINV in patients receiving moderately emetogenic chemotherapy.