Clin Cancer Res
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Results from the first-in-human phase I trial of the anti-programmed death-1 (PD-1) antibody BMS-936558 in patients with treatment-refractory solid tumors, including safety, tolerability, pharmacodynamics, and immunologic correlates, have been previously reported. Here, we provide long-term follow-up on three patients from that trial who sustained objective tumor regressions off therapy, and test the hypothesis that reinduction therapy for late tumor recurrence can be effective. ⋯ These data represent the most prolonged observation to date of patients with solid tumors responding to anti-PD-1 immunotherapy and the first report of successful reinduction therapy following delayed tumor progression. They underscore the potential for immune checkpoint blockade with anti-PD-1 to reset the equilibrium between tumor and the host immune system.
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Durable complete remission of metastatic renal cell carcinoma (RCC) has rarely been achieved with current treatment modalities. To solve this problem, alternative therapeutic options with high efficacy and minimal side effects are strongly needed. ⋯ Sequential combination gene therapy using MSC/dTRAIL-TK achieved long-term remission of metastatic RCC without noticeable toxicity. Our findings provide an innovative therapeutic approach to completely eradicate metastatic tumors by simple, repeated administrations of MSC/dTRAIL-TK.
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This study was designed to establish the maximum tolerated dose (MTD) and to evaluate tolerability, pharmacokinetics, and antitumor activity of etirinotecan pegol. ⋯ Etirinotecan pegol showed substantial antitumor activity in patients with various solid tumors and a somewhat different safety profile compared with the irinotecan historical profile. The MTD recommended for phase II clinical trials is 145 mg/m(2) q14d or q21d.
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Brentuximab vedotin (SGN-35), an intravenously administered CD30-specific antibody-drug conjugate, has recently been approved by the U. S. Food and Drug Administration for two indications, including (i) patients with Hodgkin lymphoma relapsing after autologous stem-cell transplantation (ASCT), or after two multidrug regimens in patients with Hodgkin lymphoma who are not candidates for ASCT; and (ii) patients with systemic anaplastic large cell lymphoma (ALCL) who failed at least one prior multidrug chemotherapy regimen. ⋯ The complete response rate was equally as impressive, at 34% and 57% for Hodgkin lymphoma and ALCL, respectively. Results like these and from many other upcoming clinical trials, in which brentuximab vedotin is being investigated in the frontline setting, promise to profoundly change how we manage the CD30-positive lymphoproliferative malignancies. The mechanism of action, preclinical antitumor activity, and clinical activity of brentuximab vedotin against Hodgkin lymphoma, ALCL, and other CD30-expressing lymphomas are reviewed.