Anti-CD22 90Y-epratuzumab tetraxetan combined with anti-CD20 veltuzumab: a phase I study in patients with relapsed/refractory, aggressive non-Hodgkin lymphoma.

A lingering criticism of radioimmunotherapy in non-Hodgkin lymphoma is the use of cold anti-CD20 antibody along with the radiolabeled anti-CD20 antibody. We instead combined radioimmunotherapy with immunotherapy targeting different B-cell antigens. We evaluated the anti-CD22 (90)Y-epratuzumab tetraxetan with the anti-CD20 veltuzumab in patients with aggressive lymphoma in whom at least one prior standard treatment had failed, but who had not undergone stem cell transplantation. Eighteen patients (median age 73 years, median of 3 prior treatments) received 200 mg/m(2) veltuzumab once-weekly for 4 weeks, with (90)Y-epratuzumab tetraxetan at planned doses in weeks 3 and 4, and (111)In-epratuzumab tetraxetan in week 2 for imaging and dosimetry. Veltuzumab effectively lowered levels of B cells in the blood prior to the radioimmunotherapy doses. No significant immunogenicity or change in pharmacokinetics of either agent occurred in combination. (111)In imaging showed tumor targeting with acceptable radiation dosimetry to normal organs. For (90)Y-epratuzumab tetraxetan, transient myelosuppression was dose-limiting with 6 mCi/m(2) (222 MBq/m(2)) × 2 being the maximal tolerated dose. Of 17 assessable patients, nine (53%) had objective responses according to the 2007 revised treatment response criteria, including three (18%) complete responses (2 relapsing after 11 and 13 months, 1 continuing to be clinically disease-free at 19 months), and six (35%) partial responses (1 relapsing after 14 months, 5 at 3 - 7 months). Responses occurred in patients with different lymphoma histologies, treated at different (90)Y dose levels, and with a predicted risk of poor outcome, most importantly including five of the six patients treated with the maximal tolerated dose (2 of whom achieved durable complete responses). In conclusion, the combination of (90)Y-epratuzumab tetraxetan and veltuzumab was well-tolerated with encouraging therapeutic activity in this difficult-to-treat population.

Phase II study of carboplatin, pemetrexed, and bevacizumab in advanced nonsquamous non-small-cell lung cancer.

Lung cancer remains the leading cause of cancer death throughout the world. Despite new chemotherapeutic, immunomodulating and molecularly targeted agents, patients with locally advanced or metastatic disease still have a poor prognosis. This trial looked to combine antiangiogenic therapy with a first-line cytotoxic chemotherapy doublet, hoping to extend median progression-free survival (PFS) while minimizing toxicity in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC). In this single institution, single-arm study, 51 patients (age >18 yo) were followed from 2007 to 2012. Patients with stage IV nonsquamous NSCLC and patients with recurrent unresectable disease (nonradiation candidates) were eligible. Treatment consisted of carboplatin AUC 5 IV 30-60 minutes, pemetrexed 500/mg2 IV 10 minutes, bevacizumab 15 mg/kg IV (90 minutes 1st dose, 60 minutes 2nd dose, 30 minutes subsequent doses). Treatment was administered every 21 days and planned for 6 cycles, in the absence of disease progression or unacceptable toxicities. Growth factor support was not permitted prophylactically but allowed for toxicities, as were dose reductions. Maintenance treatment for those with stable disease or better consisted of Bevacizumab 15 mg/kg every 3 weeks for up to 1 year. Between November 2007 and March 2012, 51 patients were followed in the phase II trial of carboplatin, pemetrexed, and bevacizumab. Patients were enrolled over a 24-month period. After the end of treatment visits, subjects were followed at least every 3 months for survival data. The median follow-up period was 49 weeks (6 weeks to 178), and the median number of treatment cycles was 6 (range, 1-6). Among the 50 patients assessable for response, median overall survival was 49 weeks (95% CI, 0-62.7) with median PFS of 28 weeks (95% CI, 0-132.4). A complete or partial response was seen in 28 (59.5%) patients. Grade 3-4 treatment-related adverse events occurred in 9 (17.6%) of 51 patients; the most common were thrombocytopenia (4 [7.8%]) and neutropenia (3 [5.9%]). Three (5.8%) of 51 patients were discontinued because of treatment-related adverse events (grade 3 diarrhea, thrombocytopenia, dehydration, fatigue, and grade 4 respiratory distress), and 1 patient (1.9%) was found to be ineligible due to anticoagulation use. A novel 3-drug combination for advanced nonsquamous NSCLC shows promising efficacy with modest toxicity.

Multidisciplinary management of gastric cancer.

Treatment of gastric cancer involves a multidisciplinary approach to achieve long-term outcome, including surgery, chemotherapy, and radiation therapy. Most patients present with advanced disease and are not candidates for a curative approach. Palliative chemotherapy is recommended for symptom control and for short-term advances in survival. Surgery combined with different chemotherapy and chemoradiation options improves survival. Initial studies focused on adjuvant chemoradiation and showed improved survival. More recent trials have demonstrated that perioperative chemotherapy before and after surgery provides a survival advantage. Such an approach may also downstage marginal patients who can then be selected to undergo curative resection and complete adjuvant chemotherapy.

Post-transplant lymphoproliferative disorder after lung transplantation: a review of 35 cases.

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transplantation. The risk of developing PTLD varies depending on a number of factors, including the organ transplanted and the degree of immunosuppression used. METHODS: We report a retrospective analysis of 35 patients with PTLD treated at our center after lung transplantation. Of 705 patients who received allografts, 34 (4.8%) developed PTLD. One patient underwent transplantation elsewhere and was treated at our center. RESULTS: PTLD involved the allograft in 49% of our patients and the gastrointestinal (GI) tract lumen in 23%. Histologically, 39% of tumors were monomorphic and 48% polymorphic. The time to presentation defined the location and histology of disease. Of 17 patients diagnosed within 11 months of transplantation, PTLD involved the allograft in 12 (71%) and the GI tract in 1 (p = 0.01). This "early" PTLD was 85% polymorphic (p = 0.006). Conversely, of the 18 patients diagnosed more than 11 months after transplant, the lung was involved in 5 (28%) and the GI tract in 7 (39%; p = 0.01). "Late" PTLD was 71% monomorphic (p = 0.006). Median overall survival after diagnosis was 18.57 months. Overall survival did not differ between all lung transplant recipients and those who developed PTLD. CONCLUSIONS: PTLD is an uncommon complication after lung transplantation, and its incidence declined remarkably in the era of modern immunosuppression. We report several factors that are important for predisposition toward, progression of, and treatment of PTLD after lung transplantation.