Edward A Stadtmauer

University of Pennsylvania, Filadelfia, Pennsylvania, United States

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Publications (225)1689.48 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite recent therapeutic advances, multiple myeloma (MM) remains largely incurable. Here we report results of a phase I/II trial to evaluate the safety and activity of autologous T cells engineered to express an affinity-enhanced T cell receptor (TCR) recognizing a naturally processed peptide shared by the cancer-testis antigens NY-ESO-1 and LAGE-1. Twenty patients with antigen-positive MM received an average 2.4 × 10(9) engineered T cells 2 d after autologous stem cell transplant. Infusions were well tolerated without clinically apparent cytokine-release syndrome, despite high IL-6 levels. Engineered T cells expanded, persisted, trafficked to marrow and exhibited a cytotoxic phenotype. Persistence of engineered T cells in blood was inversely associated with NY-ESO-1 levels in the marrow. Disease progression was associated with loss of T cell persistence or antigen escape, in accordance with the expected mechanism of action of the transferred T cells. Encouraging clinical responses were observed in 16 of 20 patients (80%) with advanced disease, with a median progression-free survival of 19.1 months. NY-ESO-1-LAGE-1 TCR-engineered T cells were safe, trafficked to marrow and showed extended persistence that correlated with clinical activity against antigen-positive myeloma.
    Nature medicine 07/2015; DOI:10.1038/nm.3910 · 28.05 Impact Factor
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    ABSTRACT: To characterize the impact of graft T-cell composition on outcomes of reduced-intensity conditioned (RIC) allogeneic hematopoietic stem-cell transplantation (alloHSCT) in adults with hematologic malignancies. We evaluated associations between graft T-cell doses and outcomes in 200 patients who underwent RIC alloHSCT with a peripheral blood stem-cell graft. We then studied 21 alloHSCT donors to identify predictors of optimal graft T-cell content. Higher CD8 cell doses were associated with a lower risk for relapse (adjusted hazard ratio [aHR], 0.43; P = .009) and improved relapse-free survival (aHR, 0.50; P = .006) and overall survival (aHR, 0.57; P = .04) without a significant increase in graft-versus-host disease or nonrelapse mortality. A cutoff level of 0.72 × 10(8) CD8 cells per kilogram optimally segregated patients receiving CD8(hi) and CD8(lo) grafts with differing overall survival (P = .007). Donor age inversely correlated with graft CD8 dose. Consequently, older donors were unlikely to provide a CD8(hi) graft, whereas approximately half of younger donors provided CD8(hi) grafts. Compared with recipients of older sibling donor grafts (consistently containing CD8(lo) doses), survival was significantly better for recipients of younger unrelated donor grafts with CD8(hi) doses (P = .03), but not for recipients of younger unrelated donor CD8(lo) grafts (P = .28). In addition, graft CD8 content could be predicted by measuring the proportion of CD8 cells in a screening blood sample from stem-cell donors. Higher graft CD8 dose, which was restricted to young donors, predicted better survival in patients undergoing RIC alloHSCT. © 2015 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 06/2015; 33(21). DOI:10.1200/JCO.2014.60.1203 · 18.43 Impact Factor
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    ABSTRACT: High-dose melphalan with autologous stem cell support improves survival for patients with myeloma. For selected patients, we have been using a protocol of short hospitalization, discharging patients to home with careful outpatient monitoring in the office, which we hypothesized would reduce complications and utilization of inpatient beds. We reviewed 301 initial autologous transplants for myeloma, categorized as brief stay (≤ 4 days, 82 patients) or prolonged stay (≥ 5 days, 219 patients). Selection for a brief stay was determined by clinical characteristics, availability of caregivers at home, distance from our medical center, and patient preference. Within the brief stay population, 67% required readmission before day + 100, but this group still had fewer cumulative hospital days (9 vs. 18, P < .0001). There were fewer documented infections among brief stay patients (22% vs. 46% P < .001) and fewer admissions to intensive care units (0% vs. 5.9%, P = .02). The groups had similar rates of bleeding (1.2% vs. 1.4% P = 1.0) and thrombosis (3.7% vs. 4.6% P = 1.0). No patients in the brief stay group died within 100 days, compared with mortality of 1.8% (P = .6) in the prolonged stay group. Carefully selected patients receiving an autologous stem cell transplant for treatment of myeloma can be managed with a brief initial hospitalization and outpatient follow-up, with low morbidity and mortality. Copyright © 2015 Elsevier Inc. All rights reserved.
    Clinical Lymphoma, Myeloma and Leukemia 06/2015; DOI:10.1016/j.clml.2015.05.006 · 2.02 Impact Factor
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    ABSTRACT: We examined the associations of Epstein-Barr virus (EBV) status with characteristics and outcomes of posttransplantation lymphoproliferative disorder (PTLD) by studying 176 adult solid organ transplant recipients diagnosed with PTLD between 1990 and 2013 (58 [33%] EBV-negative; 118 [67%] EBV-positive). The proportion of EBV-negative cases increased over time from 10% (1990-1995) to 48% (2008-2013) (p < 0.001). EBV-negative PTLD had distinct characteristics (monomorphic histology, longer latency) though high-risk features (advanced stage, older age, high lactate dehydrogenase, central nervous system involvement) were not more common compared to EBV-positive PTLD. In multivariable analysis, EBV negativity was not significantly associated with worse response to initial therapy (adjusted odds ratio, 0.84; p = 0.75). The likelihood of achieving a complete remission (CR) was not significantly different for EBV-negative versus EBV-positive PTLD including when therapy was reduction of immunosuppression alone (35% vs. 43%, respectively, p = 0.60) or rituximab (43% vs. 47%, p = 1.0). EBV negativity was also not associated with worse overall survival (adjusted hazard ratio, 0.91; p = 0.71). Our findings indicate that EBV status is not prognostic or predictive of treatment response in adults with PTLD. The high proportion of EBV-negative disease diagnosed in recent years highlights the need for new strategies for prevention and management of EBV-negative PTLD. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
    American Journal of Transplantation 05/2015; DOI:10.1111/ajt.13324 · 6.19 Impact Factor
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    ABSTRACT: This phase 1/2 study was the first to evaluate the safety and efficacy of the cyclin-dependent kinase (CDK) 4/6-specific inhibitor palbociclib (PD-0332991) in sequential combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma. The recommended phase 2 dose was palbociclib 100 mg orally once daily on days 1-12 of a 21-day cycle with bortezomib 1.0 mg/m(2) (intravenous) and dexamethasone 20 mg (orally 30 min pre-bortezomib dosing) on days 8 and 11 (early G1 arrest) and days 15 and 18 (cell cycle resumed). Dose-limiting toxicities were primarily cytopenias; most other treatment-related adverse events were grade ≤3. At a bortezomib dose lower than that in other combination therapy studies, antitumor activity was observed (phase 1). In phase 2, objective responses were achieved in 5 (20%) patients; 11 (44%) achieved stable disease. Biomarker and pharmacodynamic assessments demonstrated that palbociclib inhibited CDK4/6 and the cell cycle initially in most patients. ClinicalTrials.gov number=NCT00555906.
    Leukemia & lymphoma 03/2015; DOI:10.3109/10428194.2015.1030641 · 2.89 Impact Factor
  • Biology of Blood and Marrow Transplantation 02/2015; 21(2):S42-S43. DOI:10.1016/j.bbmt.2014.11.036 · 3.35 Impact Factor
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    ABSTRACT: The incidence and risk factors for acute cholecystitis following allogeneic hematopoietic stem cell transplantation (HSCT) are not well defined. Of 644 consecutive adult transplants performed at our institution between 2001 and 2011, acute cholecystitis occurred in the first year of transplant in 32 patients (5.0%). We conducted two retrospective case-control studies of this population to determine risk factors for cholecystitis after HSCT and to evaluate the performance of difference methods of imaging to diagnosis cholecystitis in patients undergoing HSCT compared to non-HSCT patients. In the HSCT population, development of cholecystitis was associated with an increased 1-year overall mortality rate (62.5% vs. 19.8%, p<0.001). The risk of developing cholecystitis was higher in patients who received total parenteral nutrition (TPN) (adjusted OR, 3.41; p=0.009). There was a trend towards more equivocal abdominal ultrasound (US) findings in HSCT recipients with acute cholecystitis compared to non-transplant patients (50.0% vs. 30.6%, p=0.06). However, HIDA scans were definitively positive for acute cholecystitis in most patients in both populations (80.0% of HSCT recipients vs. 77.4% of controls, p =0.82). In conclusion, acute cholecystitis is a common early complication of HSCT, the risk is increased in patients who receive TPN, and it is associated with high 1-year mortality. In HSCT recipients with findings suggestive of acute cholecystitis, especially those receiving TPN, early use of HIDA scan may be considered over US. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 12/2014; 21(4). DOI:10.1016/j.bbmt.2014.12.005 · 3.35 Impact Factor
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    ABSTRACT: Background Circulating plasma cells (PCs) have been identified as a prognostic factor in patients with myeloma precursor states (MGUS and SMM) and active multiple myeloma (MM). Enumeration of circulating PCs by available methods is not suitable for widespread use and does not provide molecular characterization. We developed and evaluated a novel method for enumeration and molecular characterization of circulating PCs (circulating multiple myeloma cells, “CMMC”), based on the CELLSEARCH® System (Janssen Diagnostics LLC, Raritan, NJ), an automated technology for the capture, enumeration and characterization of rare cells in the peripheral blood. Methods We are performing a prospective study of patients with MGUS and SMM to evaluate CMMCs as biomarker for progression to active MM. Utilizing the CELLSEARCH® System CMMCs were captured by CD138 ferrofluid magnetic particles and identification was defined as CD38+ and CD19-, CD45-. Nonviable cells were excluded by DAPI. Isolated CMMCs were stored and FISH for t(4:14), t(14;16) and del17 was performed. Results We have enrolled 16 patients, MGUS = 3, SMM = 11, and newly diagnosed MM = 2. The Mayo Risk stratification for MGUS patients was: low risk = 2, low-intermediate = 1. All SMM patients were low risk by Mayo Model incorporating serum free light chains. The median number of bone marrow plasma cells for MGUS patients was 7 (range 7-9) and for SMM patients was 15 (range 10-40). The median CMMCs for MGUS = 6 (range 2-55), median CMMCs for SMM = 31 (5-1918). The two patients with NDMM had 5870 and 5 CMMCs, respectively. A single patient with SMM progressed with a symptomatic solitary lumbar plasmacytoma and had CMMCs of 5 and 3 at baseline and progression, respectively. Abnormalities by FISH were detected in both bone marrow and CMMCs. Accrual is ongoing and additional data will be presented at the meeting. Conclusions The CELLSEARCH® CMMC assay can detect, quantify and provide molecular characterization of circulating PCs in MGUS/SMM/MM; longer prospective follow-up is needed to test the prognostic value of CMMCs. Disclosures Weiss: Janssen: Consultancy, Research Funding. Sasser: Janssen: Employment. Rao: Janssen: Employment, Equity Ownership. Foulk: Janssen: Employment. Gross: Johnson & Johnson: Employment, Equity Ownership. Cohen: Janssen: Membership on an entity's Board of Directors or advisory committees. Vogl: Celgene Corporation: Consultancy; Amgen: Consultancy; Millennium/Takeda: Research Funding; GSK: Research Funding; Acetylon: Research Funding. Stadtmauer: Janssen: Consultancy.
    Blood 12/2014; 124(21):2031-2031. · 10.43 Impact Factor
  • Daniel J. Landsburg · Dan T. Vogl · John P. Plastaras · Edward A. Stadtmauer
    Clinical Lymphoma, Myeloma and Leukemia 12/2014; 14(6). DOI:10.1016/j.clml.2014.07.012 · 2.02 Impact Factor
  • A J Waxman · R Mick · A L Garfall · A Cohen · D T Vogl · E A Stadtmauer · B M Weiss
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    ABSTRACT: Leukemia is one of the leading journals in hematology and oncology. It is published monthly and covers all aspects of the research and treatment of leukemia and allied diseases. Studies of normal hemopoiesis are covered because of their comparative relevance.
    Leukemia 11/2014; 29(3). DOI:10.1038/leu.2014.313 · 9.38 Impact Factor
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    ABSTRACT: Advances in the past decade and a half have led to unprecedented improved outcomes for patients with multiple myeloma (MM), and this disease appears to be transitioning to one more characteristic of a chronic disease in large part due to rapid translation of clinical insights into practice at the community level. Although evidence-based guidelines and consensus recommendations remain an important resource for managing cancer patients, they do not fill the gap between the principles of disease management today and the translation of tailoring treatment for individual patient needs. Thus, there is a continuing need for concise, focused educational activities and resources that facilitate improved knowledge and understanding of appropriate, individualized therapeutic strategies for assessing and caring for patients with MM. The next several years will truly be a time of shifting paradigms in the treatment of MM in which new agents will be approved, response criteria will be updated, and new approaches to risk assessment and monitoring minimal residual disease will evolve and enter practice. New groundbreaking therapeutic approaches, such as immunotherapy, might result in significant changes in how MM is treated and managed over the entire life cycle of the disease. Even the definition of the disease might be further amended as insights grow regarding who should be treated and who might benefit more from observation. As such, oncology clinicians will have to carefully review and update their management approaches accordingly even as they begin to focus even more on the survivorship needs of their MM patients.
    Clinical Lymphoma, Myeloma and Leukemia 10/2014; 14(5). DOI:10.1016/j.clml.2014.04.011 · 2.02 Impact Factor
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    ABSTRACT: Recombinant herpes zoster (HZ) vaccines may be an alternative to the live-attenuated HZ vaccine for immunocompromised individuals.This was a phase 1/2, randomized, observer-blind, placebo-controlled study in adults with multiple myeloma, non-Hodgkin lymphoma (B- or T-cell), Hodgkin lymphoma, or acute myeloid leukemia who had undergone autologous hematopoietic stem-cell transplant 50-70 days earlier. Subjects (N=121) were randomized 1:1:1:1 to receive (at months 0, 1, 3) three doses of 50 µg VZV glycoprotein E (gE) adjuvanted with AS01B, three doses of gE adjuvanted with AS01E, one dose of saline followed by two doses of gE/AS01B, or three doses of saline. One month after the last dose (6 months after transplant), frequencies of CD4(+) T cells expressing ≥2 activation markers following induction with gE and anti-gE antibody concentrations were higher with all gE/AS01 regimens than with saline. Both responses persisted up to one year in subjects vaccinated with gE/AS01. Immune responses were higher in the gE/AS01B 3-dose group than in the gE/AS01B 2-dose group but not higher than in the gE/AS01E 3-dose group. One serious adverse event (pneumonia) was considered vaccine-related. Both formulations and both schedules were immunogenic and well tolerated in this population. This study was registered at Clinicaltrials.gov as #NCT00920218.
    Blood 09/2014; 124(19). DOI:10.1182/blood-2014-04-573048 · 10.43 Impact Factor
  • Leukemia and Lymphoma 09/2014; 56(5):1-5. DOI:10.3109/10428194.2014.963577 · 2.89 Impact Factor
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    ABSTRACT: Patients with multiple myeloma (MM) who relapse after autologous transplantation have limited therapeutic options. We conducted a prospective, multicenter, Phase IIa study to investigate the safety and efficacy of intravenous (IV) busulfan (Bu) in combination with bortezomib as a conditioning regimen for a second autotransplant. Because a safe Bu exposure was unknown in patients receiving this combination, Bu was initially targeted to a total area under the concentration–time curve (AUC) of 20,000 μM*min. As no concentration-limiting toxicity was observed in six patients, this Bu exposure was utilized in the following treatment cohort (n=24). Individualized Bu dose, based on test dose 0.8 mg/kg pharmacokinetics [PK], was administered daily for 4 consecutive days starting 5 days before transplant, followed by a single dose of bortezomib (1.3 mg/m2) 1 day before transplantation. The total mean dose of IV Bu (including the test dose and 4-day administration) was 14.2 mg/kg (standard deviation=2.48; range 8.7–19.2). Confirmatory PK demonstrated that only 2 of 30 patients who underwent transplantation were dosed outside the Bu AUC target and dose adjustments were made for the last two doses of IV Bu. The median age was 59 years (range, 48–73). Median time from first to second transplant was 28.0 months (range, 12–119). Of 26 evaluable patients, 10 patients attained a partial response (PR) or better at 3 months post-transplantation, with two patients attaining a complete response. At 6 months post-transplantation, five of 12 evaluable patients had maintained or improved their disease status. Median progression-free survival was 191 days, whereas median overall survival was not reached during the study period. The most common grade 3–4 toxicities were febrile neutropenia (50.0%) and stomatitis (43.3%). One transplant-related death was observed. A combination of dose-targeted IV Bu and bortezomib induced PR or better in a third of patients with MM who underwent a second autotransplant, with acceptable toxicity.
    Biology of Blood and Marrow Transplantation 08/2014; 20(12). DOI:10.1016/j.bbmt.2014.08.007 · 3.35 Impact Factor
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    ABSTRACT: Background While intensive induction and ASCT prolong survival in younger patients with mantle cell lymphoma (MCL), benefit in older patients remains uncertain as data supporting these approaches come almost exclusively from younger cohorts. Patients and Methods We reviewed outcomes for 38 patients age ≥60 with MCL receiving R-CHOP (n=19) or R-HyperCVAD (n=19) with or without ASCT. Results Median progression free survival (PFS) of R-CHOP+ASCT (3.2 years) and R-HyperCVAD alone (4.0 years) was longer than for R-CHOP alone (1.6 years, p=0.013 and 0.009, respectively). R-CHOP+ASCT and R-HyperCVAD have similar PFS (p=0.66). R-HyperCVAD induction led to a higher incidence of toxicity including therapy discontinuation and need for transfusions as compared to R-CHOP, although rates of adverse events were similar for R-HyperCVAD alone vs. R-CHOP+ASCT. Conclusion R-CHOP alone is less effective therapy for fit older patients with MCL. Intensifying therapy with R-HyperCVAD induction or ASCT consolidation following R-CHOP is associated with prolonged PFS and similar rates of toxicity. Consideration should be given to individual preferences regarding the differing method of administration and relative timing of toxicity with each regimen.
    Clinical Lymphoma, Myeloma and Leukemia 08/2014; 15(2). DOI:10.1016/j.clml.2014.07.017 · 2.02 Impact Factor
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    ABSTRACT: Bone Marrow Transplantation is a high quality, peer-reviewed journal covering all aspects of clinical and basic haemopoietic stem cell transplantation.
    Bone Marrow Transplantation 07/2014; 49(11). DOI:10.1038/bmt.2014.153 · 3.47 Impact Factor
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    ABSTRACT: The success of hematopoietic stem-cell transplantation (HSCT) with reduced-intensity conditioning (RIC) is limited by a high rate of disease relapse. Early risk assessment could potentially improve outcomes by identifying appropriate patients for pre-emptive strategies that may ameliorate this high risk. Using a series of landmark analyses, we investigated the predictive value of early (day-30) donor chimerism measurements on disease relapse, graft-versus-host disease and survival in a cohort of 121 patients who were allografted with a uniform RIC regimen. Chimerism levels were analyzed as continuous variables. In multivariate analysis, day-30 whole blood chimerism levels were significantly associated with relapse (HR=0.90, p<0.001), relapse-free survival (HR=0.89, p<0.001) and overall survival (HR=0.94, p=0.01). Day-30 T-cell chimerism levels were also significantly associated with relapse (HR=0.97, p=0.002), relapse-free survival (HR=0.97, p<0.001) and overall survival (HR=0.99, p=0.05). Multivariate models that included T-cell chimerism provided a better prediction for these outcomes compared to whole blood chimerism. Day-30 chimerism levels were not associated with acute or chronic graft-versus-host disease. We found that high donor chimerism levels were significantly associated with a low lymphocyte count in the recipient prior to transplant, highlighting the impact of pre-transplant lymphopenia on the kinetics of engraftment after RIC HSCT. In summary, low donor chimerism levels are associated with relapse and mortality and can potentially be used as an early predictive and prognostic marker. These findings can be used to design novel approaches to prevent relapse and to improve survival after RIC HSCT.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 07/2014; 20(11). DOI:10.1016/j.bbmt.2014.07.003 · 3.35 Impact Factor
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    ABSTRACT: The efficacy of proteasome inhibition for myeloma is limited by therapeutic resistance, which may be mediated by activation of the autophagy pathway as an alternative mechanism of protein degradation. Preclinical studies demonstrate that autophagy inhibition with hydroxychloroquine augments the antimyeloma efficacy of the proteasome inhibitor bortezomib. We conducted a phase I trial combining bortezomib and hydroxychloroquine for relapsed or refractory myeloma. We enrolled 25 patients, including 11 (44%) refractory to prior bortezomib. No protocol-defined dose-limiting toxicities occurred, and we identified a recommended phase 2 dose of hydroxychloroquine 600 mg twice daily with standard doses of bortezomib, at which we observed dose-related gastrointestinal toxicity and cytopenias. Of 22 patients evaluable for response, 3 (14%) had very good partial responses, 3 (14%) had minor responses, and 10 (45%) had a period of stable disease. Electron micrographs of bone marrow plasma cells collected at baseline, after a hydroxychloroquine run-in, and after combined therapy showed therapy-associated increases in autophagic vacuoles, consistent with the combined effects of increased trafficking of misfolded proteins to autophagic vacuoles and inhibition of their degradative capacity. Combined targeting of proteasomal and autophagic protein degradation using bortezomib and hydroxychloroquine is therefore feasible and a potentially useful strategy for improving outcomes in myeloma therapy.
    Autophagy 05/2014; 10(8). DOI:10.4161/auto.29264 · 11.42 Impact Factor
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    ABSTRACT: Allogeneic hematopoietic cell transplantation (alloHCT) with reduced intensity conditioning is an appealing option for patients with high risk multiple myeloma (MM). However, progression after alloHCT remains a challenge. Maintenance therapy after alloHCT may offer additional disease control and allow time for a graft-versus-myeloma effect. The primary objective of this clinical trial was to determine the tolerability and safety profile of maintenance lenalidomide (LEN) given on days 1-21 of 28 days cycles, with intra-patient dose escalation during 12 months/cycles after alloHCT. Thirty alloHCT recipients (median age 54 years) with high risk MM were enrolled at 8 centers between 2009 -2012. The median time from alloHCT to LEN initiation was 96 days (66-171 days). Eleven patients (37%) completed maintenance and 10 mg daily was the most commonly delivered dose (44%).Most common reasons for discontinuation were aGVHD (37%) and disease progression (37%). Cumulative incidence of grades III-IV acute GVHD from time of initiation of Len was 17%. . Outcomes at 18 months after initiation of maintenance were MM progression, 28%; transplant related mortality, 11%; and progression-free and overall survival, 63% and 78%, respectively. The use of LEN post alloHCT is feasible at lower doses, although associated with a 38% incidence of aGVHD. Survival outcomes observed in this high risk MM population warrant further study of this approach.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 04/2014; 20(8). DOI:10.1016/j.bbmt.2014.04.014 · 3.35 Impact Factor
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    ABSTRACT: Myeloma-directed cellular immune responses after autologous stem cell transplantation (ASCT) may reduce relapse rates. We studied whether coinjecting the TLR-3 agonist and vaccine adjuvant Poly-ICLC with a MAGE-A3 peptide vaccine was safe and would elicit a high frequency of vaccine-directed immune responses when combined with vaccine-primed and costimulated autologous T cells.EXPERIMENTAL DESIGN: In a phase II clinical trial (NCT01245673), we evaluated the safety and activity of ex vivo expanded autologous T cells primed in vivo using a MAGE-A3 multipeptide vaccine (compound GL-0817) combined with Poly-ICLC (Hiltonol), granulocyte macrophage colony-stimulating factor (GM-CSF) ± montanide. Twenty-seven patients with active and/or high-risk myeloma received autografts followed by anti-CD3/anti-CD28-costimulated autologous T cells, accompanied by MAGE-A3 peptide immunizations before T-cell collection and five times after ASCT. Immune responses to the vaccine were evaluated by cytokine production (all patients), dextramer binding to CD8(+) T cells, and ELISA performed serially after transplant.RESULTS: T-cell infusions were well tolerated, whereas vaccine injection site reactions occurred in >90% of patients. Two of nine patients who received montanide developed sterile abscesses; however, this did not occur in the 18 patients who did not receive montanide. Dextramer staining demonstrated MAGE-A3-specific CD8 T cells in 7 of 8 evaluable HLA-A2(+) patients (88%), whereas vaccine-specific cytokine-producing T cells were generated in 19 of 25 patients (76%). Antibody responses developed in 7 of 9 patients (78%) who received montanide and only weakly in 2 of 18 patients (11%) who did not. The 2-year overall survival was 74% [95% confidence interval (CI), 54%-100%] and 2-year event-free survival was 56% (95% CI, 37%-85%).CONCLUSIONS: A high frequency of vaccine-specific T-cell responses were generated after transplant by combining costimulated autologous T cells with a Poly-ICLC/GM-CSF-primed MAGE-A3 vaccine. Clin Cancer Res; 1-11. ©2013 AACR.
    Clinical Cancer Research 02/2014; 20(5). DOI:10.1158/1078-0432.CCR-13-2817 · 8.19 Impact Factor

Publication Stats

11k Citations
1,689.48 Total Impact Points

Institutions

  • 2000–2015
    • University of Pennsylvania
      • • Perelman School of Medicine
      • • "Abramson" Cancer Center
      • • Division of Hematology/Oncology
      Filadelfia, Pennsylvania, United States
  • 2003–2014
    • William Penn University
      Filadelfia, Pennsylvania, United States
  • 1994–2014
    • Hospital of the University of Pennsylvania
      • • Division of Hematology/Oncology
      • • Department of Medicine
      Philadelphia, Pennsylvania, United States
  • 2002–2013
    • Columbia University
      • Department of Pathology & Cell Biology
      New York City, New York, United States
  • 2011
    • University of Texas MD Anderson Cancer Center
      Houston, Texas, United States
  • 2010
    • Loyola University Maryland
      Baltimore, Maryland, United States
  • 2009
    • Treatment Research Institute, Philadelphia PA
      Filadelfia, Pennsylvania, United States
  • 2005–2006
    • The Children's Hospital of Philadelphia
      Filadelfia, Pennsylvania, United States
    • University of Maryland Medical Center
      Baltimore, Maryland, United States
    • Emory University
      Atlanta, Georgia, United States
  • 2001
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
  • 1989–1999
    • University of California, Los Angeles
      • Department of Medicine
      Los Ángeles, California, United States
  • 1997
    • Medical College of Wisconsin
      • Center for International Blood & Marrow Transplant Research
      Milwaukee, Wisconsin, United States
  • 1995
    • University Center Rochester
      Рочестер, Minnesota, United States