Citations 12
Clinical Activity of Single Dose Systemic Oncolytic VSV Virotherapy in Patients with Relapsed Refractory T-Cell Lymphoma
Peng, Kah Whye, Witzig, Thomas E. , Broski, Stephen M. , Villasboas, José C. , Patnaik, Mrinal M. , Leung, Nelson , Ansell, Stephen M. , Zhang, Lianwen , Brunton, Bethany, Giers, Marissa, Ginos, Brenda, Dueck, Amylou C. , Geyer, Susan M. , Warsame, Rahma , Hayman, Suzanne R. , Dingli, David , Kumar, Shaji , Bergsagel, P. Leif , Kourelis, Taxiarchis , Kapoor, Prashant , Kyle, Robert A. , Lin, Yi , Siddiqui, Mustaqeem , Fonder, Amie , Hobbs, Miriam, Hwa, Yi L. , Naik, Shruthi , Russell, Stephen J. , Lacy, Martha Q. , Bergsagel, P. Leif , Witzig, T.E. , Broski, Stephen M , Villasboas, Jose Caetano , Paludo, Jonas , Patnaik, Mrinal , Dispenzieri, Angela , Leung, Nelson , Buadi, Francis K , Bennani, N Nora , Balakrishnan, Baskar , Dueck, A. C. , Gertz, Morie A , Warsame, Rahma , Kumar, Shaji K , Munoz, Javier L, Kourelis, Taxiarchis , Muchtar, E , Siddiqui, Mustaqeem A , Fonder, Amie , Russell, Stephen J , Lacy, Martha Q , Dingli, David , Lin, Yi , Cook, Joselle , Paludo, Jonas , Rajkumar, S. Vincent , Dispenzieri, Angela , Buadi, Francis K. , Bennani, N. Nora , Packiriswamy, Nandakumar , Balakrishnan, Baskar , Gertz, Morie A. , Go, Ronald S. , Muñoz, Javier , Gonsalves, Wilson I. , Muchtar, Eli
Blood Advances | February 17, 2022 | Volume: No volume available | Issue: No issue available | Pages: No page available
10.1182/bloodadvances.2021006631
Clinical success with intravenous (IV) oncolytic virotherapy (OV) has to date been anecdotal. Here, we conducted a phase 1 clinical trial of systemic OV therapy and investigated the mechanisms of action in responding T-cell lymphoma (TCL) patients. A single IV dose of VSV-IFNβ-NIS was administered to patients with relapsed refractory hematologic malignancies to determine safety and efficacy across 4 dose levels (DL). Correlative studies were undertaken to evaluate viremia, virus shedding, virus replication and immune responses. Fifteen patients received VSV-IFNβ-NIS (7 multiple myeloma, 7 TCL, 1 acute myeloid leukemia); 3 patients were treated at each DL1 through DL3 (0.05, 0.17, and 0.5 x 1011 TCID50), and 6 at DL4 (1.7 x 1011 TCID50). There were no dose limiting toxicities. 3 of 7 patients with TCL had RECIST responses: a 3-month PR at DL2, a 6-month PR and a durable CR ongoing at 20 months at DL4. Viremia peaked at the end of infusion and no infectious virus shedding was detected. Plasma interferon-β levels, a biomarker of VSV-IFNβ-NIS replication, peaked between 4h and 48h post infusion. The patient with CR had robust viral replication with increased ell free DNA in her plasma, a very high peak IFNβ level of 18,213 pg/ml, a strong anti-VSV neutralizing antibody response, and increased numbers of tumor reactive T-cells. VSV-IFNβ-NIS as a single agent was effective in patients with TCL resulting in durable disease remissions in heavily pretreated patients. Correlative analyses suggest that responses may be due to a combination of direct oncolytic tumor destruction and immune-mediated tumor control. Further clinical testing is warranted. (This trial is registered at www.clinicaltrials.gov as NCT03017820).
Prognostic impact of posttransplant FDG PET/CT scan in multiple myeloma
Kaddoura, Marcella , Dingli, David , Buadi, Francis K. , Lacy, Martha Q. , Kapoor, Prashant , Hwa, Yi L. , Fonder, Amie , Hobbs, Miriam, Hayman, Suzanne R. , Lust, John A., Lin, Yi , Kourelis, Taxiarchis , Warsame, Rahma , Kyle, Robert A. , Kumar, Shaji , Dispenzieri, Angela , Fonder, Amie , Leung, Nelson , Kourelis, Taxiarchis , Broski, Stephen M , Rajkumar, S Vincent , Kumar, Shaji K , Tschautscher, Marcella , Buadi, Francis K , Dingli, David , Lin, Yi , Gertz, Morie A. , Dispenzieri, Angela , Leung, Nelson , Go, Ronald S. , Gonsalves, Wilson I. , Broski, Stephen M. , Rajkumar, S. Vincent
Blood Advances | July 10, 2021 | Volume: 5 | Issue: 13 | Pages: 2753-2759
10.1182/bloodadvances.2020004131
Abstract Multiple myeloma (MM) is a heterogeneous disease that may be evaluated by a broad array of imaging and laboratory techniques to measure disease activity and predict prognosis. Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scanning has been shown to be predictive of patient outcomes throughout the disease course. We sought to corroborate these findings by examining the prognostic impact of PET/CT scanning in the posttransplant setting. We retrospectively analyzed PET/CT scans in 229 MM patients receiving an autologous stem cell transplant (ASCT) near day 100, and correlated these findings with time to progression(TTP) and overall survival (OS) to assess the impact of day 100 PET/CT scan findings as an independent prognostic factor. The median OS for the entire cohort was 61.5 months (95% confidence interval [CI], 49-75) and the median TTP was 18.5 months (95% CI, 15.4-21.8). Among patients with abnormal day 100 PET findings (PET+), median TTP was 12.4 months vs 24 months among those with normal PET findings (PET−) (P < .0001). The median OS in the PET+ group was 46 months compared with 99 months in the PET− group (P < .0001). We conclude that an abnormal PET/CT scan near day 100 post-ASCT is predictive of shorter TTP and OS, with prognostic significance retained after adjusting for disease response and other prognostic variables in MM.