Papers by Stephen Schuster
Blood, May 20, 2021
Intolerance is the most common reason for kinase inhibitor (KI) discontinuation in chronic lympho... more Intolerance is the most common reason for kinase inhibitor (KI) discontinuation in chronic lymphocytic leukemia (CLL). Umbralisib, a novel highly selective phosphatidylinositol 3-kinase d (PI3Kd)/CK1« inhibitor, is active and well tolerated in CLL patients. In this phase 2 trial (NCT02742090), umbralisib was initiated at 800 mg/d in CLL patients requiring therapy, who were intolerant to prior BTK inhibitor (BTKi) or PI3K inhibitor (PI3Ki) therapy, until progression or toxicity. Primary end point was progression-free survival (PFS). Secondary end points included time to treatment failure and safety. DNA was genotyped for CYP3A4, CYP3A5, and CYP2D6 polymorphisms. Fifty-one patients were enrolled (44 BTKi intolerant and 7 PI3Kdi intolerant); median age was 70 years (range, 48-96), with a median of 2 prior lines of therapy (range, 1-7), 24% had del17p and/or TP53 mutation, and 65% had unmutated IGHV. Most common adverse events (AEs) leading to prior KI discontinuation were rash (27%), arthralgia (18%), and atrial fibrillation (16%). Median PFS was 23.5 months (95% CI, 13.1-not estimable), with 58% of patients on umbralisib for a longer duration than prior KI. Most common (‡5%) grade ‡3 AEs on umbralisib (all causality) were neutropenia (18%), leukocytosis (14%), thrombocytopenia (12%), pneumonia (12%), and diarrhea (8%). Six patients (12%) discontinued umbralisib because of an AE. Eight patients (16%) had dose reductions and were successfully rechallenged. These are the first prospective data to confirm that switching from a BTKi or alternate PI3Ki to umbralisib in this BTKi-and PI3Ki-intolerant CLL population can result in durable well-tolerated responses.
Refractory Cytokine Release Syndrome in Recipients of Chimeric Antigen Receptor (CAR) T Cells
Blood, Dec 6, 2014
CTLO19 cells are CAR-modified T cells which recognize CD19 and produce high durable remission rat... more CTLO19 cells are CAR-modified T cells which recognize CD19 and produce high durable remission rates for pts with relapsed or refractory acute lymphoblastic leukemia (ALL). Cytokine Release Syndrome (CRS) has emerged as the major treatment related effect from CTL019, with symptoms that include high fevers and malaise but can progress to capillary leak, hypoxia and hypotension. CRS occurs hours to days after CTL019 infusion and correlates with rapid in vivo CTL019 expansion and marked elevation of serum IL6. In most cases, CRS is self-limited or rapidly reversed with anti-cytokine directed therapies. Here we report 3 cases of refractory CRS in adult pts with ALL. Our experience offers insight into clinical and investigational parameters describing this syndrome; highlights the variance of CRS across disease types and illustrates complexities of CRS management during concurrent infectious illness. As of 7/1/14, 97 pts (30 pediatric ALL, 12 adult ALL, 41 CLL, 14 NHL) have been treated with CTLO19. To capture clinical manifestations of CRS across protocols, we developed a novel CRS grading scale which will be described. Severe CRS (Gr 3-5) occurred in 27 (64%) of ALL pts and only 16 (29%) of CLL/NHL pts (p=0.001). 12 adults with ALL received CTL019; 8/9 evaluable pts achieved CR (MRD negative) at 1 month and 1 pt with extramedullary disease had marked reduction of PET avid disease which is maintained at 1 yr. Severe CRS occurred in 11 of 12 adult ALL pts. CRS was self-limited in 2 pts, rapidly reversed with anti-IL6 directed therapy in 6 pts and was refractory to therapy, contributing to death in 3 pts who were not evaluable for disease response. No baseline attributes differentiate these 3 pts from the 9 adult ALL pts with manageable Gr1-4 CRS. We have shown however that ALL disease burden correlates with CRS severity (in press) and all 3 pts had significant disease burden at baseline. All received lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2 q12h x 6 followed by infusion of CTLO19 cells. These 3 pts each received 6.50E+06, 6.70E+06 and 8.45E+06 CTLO19 cells/kg compared to median CTL019 dose of 3.62E+06 in the 9 adult ALL pts with manageable CRS. Pt 21413-03 developed CRS 12 hrs after infusion and tested positive for influenza B on D3. Despite broad spectrum antimicrobials (including oseltamivir) and anticytokine directed therapy with tocilizumab (4mg/kg x 2) and steroids, he died with refractory hypotension on D5. Pt 21413-06 had extensive disease after 2 prior allogeneic SCTs and developed CRS within 12 hrs of infusion. In addition to broad spectrum antibiotics, she received tocilizumab 8mg/kg (D 3, 6 and 12); intermittent high dose steroids (D 4-15) and etanercept (D14). She died D15 with hypotension, hypoxic respiratory failure and concurrent MDR pseudomonas sepsis and pneumonia. Pt 21413-11 developed CRS within 24 hrs of infusion. He received tocilizumab 8mg/kg (D3&4); siltuximab (D5&15) and intermittent high dose steroids (D 4-15). After an initial response, he developed recurrent fever, pulmonary infiltrates and blood cultures positive for stenotrophomonas. He died D15 with refractory hypoxia and hypotension. All 3 pts’ clinical CRS correlated with marked in vivo CTL019 expansion and progressive serum cytokine elevations (data to be shown). CONCLUSIONS: CRS is the major toxicity of CTL019 therapy and its clinical course varies depending on disease type (more frequent and severe in ALL) and disease burden (in ALL). The 3 refractory CRS cases described here (of 97 total pts treated) have all occurred in adult ALL pts with significant disease burden who received relatively high doses of CTL019 cells. In addition, all 3 had significant infectious complications which potentially fueled underlying CRS and/or were made more virulent due to impairment of immunity with administration of anti-cytokine directed therapies. Future protocol modifications will be made goal of limiting severity of CRS while maintaining high durable remission rates. Further exploration is planned to better correlate timing and choice of anticytokine directed therapy in relation to clinical and investigation parameters of CRS. Disclosures Frey: Novartis: Research Funding. Off Label Use: USe of CART19 cells to treat CLL. Levine:Novartis: Patents & Royalties, Research Funding. Lacey:Novartis: Research Funding. Grupp:Novartis: Consultancy, Research Funding. Schuster:Novartis: Research Funding. Hwang:NVS: Research Funding. Leung:Novartis: Employment. Shen:Novartis: Employment. Ericson:Novartis: Employment. Melenhorst:Novartis: Research Funding. June:Novartis: Patents & Royalties, Research Funding. Porter:Novartis: Patents & Royalties, Research Funding.
Posttransplant lymphoproliferative disorder in adult liver transplant recipients: A report of seventeen cases
Leukemia & Lymphoma, 2007
Posttransplant lymphoproliferative disorder (PTLD) is a major complication of liver transplantati... more Posttransplant lymphoproliferative disorder (PTLD) is a major complication of liver transplantation, but previous descriptions have been limited to case reports and small case series. We report a retrospective analysis of 17 consecutive cases of PTLD associated with liver transplantation. The median age at PTLD diagnosis was 47 years (range 19 - 63) with a median time of 25 months from liver transplantation to PTLD diagnosis (range 3 - 75). PTLD location was frequently extranodal (71%) and involved the transplanted liver (41%). PTLD histology consisted of nine (53%) monomorphic and eight (47%) polymorphic disease. EBV was present by in situ hybridization in 11 (79%) of 14 cases evaluated. Initial therapy included reduction in immunosuppression (RI) alone in 13 (76%) of 17 patients, resulting in 6 (46%) complete responses (CR) and 7 (54%) progressive disease (PD). Monoclonal CD20 antibody (rituximab) and CHOP chemotherapy were used as initial therapy or as second line after RI failure. Currently, five patients (29%) are alive in CR. Although detection and treatment of PTLD in liver transplant recipients remains problematic and upfront mortality is still high, long-term survival is possible. Further studies are necessary to better define treatment strategies.
Sustained Remissions Following Chimeric Antigen Receptor Modified T Cells Directed Against CD19 (CTL019) in Patients with Relapsed or Refractory CD19+ Lymphomas
Blood, Dec 3, 2015
BACKGROUND: Autologous T cells genetically modified to express a chimeric antigen receptor consis... more BACKGROUND: Autologous T cells genetically modified to express a chimeric antigen receptor consisting of an external anti-CD19 single chain antibody domain with CD3ζ and 4-1BB signaling domains (CTL019 cells) can mediate potent anti-tumor effects in patients (pts) with relapsed or refractory chronic lymphocytic and acute lymphoblastic leukemias. We are conducting a phase IIa clinical trial to evaluate the safety and efficacy of CTL019 cells in pts with relapsed or refractory CD19+ non-Hodgkin lymphomas (NHL). METHODS: Pts with CD19+ diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), or mantle cell lymphoma (MCL) with no available curative treatment options, a limited prognosis (<2 years anticipated survival), and responsive or stable disease with most recent therapy are eligible. Pts with DLBCL have residual disease after primary and salvage therapies and are not eligible for autologous stem cell transplant (ASCT) or have relapsed or residual disease after ASCT; FL pts have progression of lymphoma <2 years after second or higher line of therapy (not including single agent monoclonal antibody therapy); MCL pts have relapsed, residual, or progressive disease after rituximab-chemotherapy combination therapy and are not appropriate for transplant or have relapsed after transplant. After steady state apheresis to collect peripheral blood leukocytes, pts receive lymphodepleting chemotherapy based on disease burden, histology, and past therapies. One to 4 days after chemotherapy, pts receive a single dose of CTL019 cells by intravenous infusion. Peripheral blood and marrow samples are collected for immunophenotypic, cytokine, and molecular studies at pre-specified times after T cell infusion. Initial tumor response assessment is performed 3 months after T cell infusion using International Working Group response criteria. Enrollment started in February 2014; data reported here are through July 26, 2015. RESULTS: To date, 38 pts have enrolled (DLBCL 21; FL 14; MCL 3). The median age is 56 years (range: 25-77), male: female ratio is 22:16, median number of prior therapies is 4 (range: 1-10), and number of pts with prior transplant is 12 (32%; 11 ASCT, 1 allotransplant). Ann Arbor stages at enrollment are: Stage IV 23 pts (61%), Stage III 7 pts (18%), Stage II 6 pts (16%), Stage 1E 2 pts (5%); 11 pts (29%) had bone marrow involvement. LDH was increased in 28 pts (74%). ECOG PS was 0 in 16 pts (42%) and 1 in 22 pts (58%). As of July 26, 2015, 24 patients have received the protocol-specified dose of CTL019 cells (13 DLBCL; 9 FL; 2 MCL). Lymphodepleting chemotherapy regimens were bendamustine (6 pts), cyclophosphamide (11 pts), cyclophosphamide-fludarabine (1 pt), modified EPOCH (3 pts), and radiation-cyclophosphamide (3 pts). Median total CTL019 cell dose is 5.00e8 (range: 1.79e8 - 5.00e8); median CTL019 cell dose/kg is 5.84e6 (range: 3.08e6-8.87e6). Median peak CTL019 cell expansion in blood occurred 7 days after infusion (range: 2-14 days); there was no difference in peak expansion between responders and non-responders. Cytokine release syndrome (CRS) occurred in 16 pts (14 grade 2; 1 grade 3; 1 grade 4) and did not predict response. Neurologic toxicity occurred in 3 pts: 2 episodes of delirium (1 grade 2, 1 grade 3) and one possibly related grade 5 encephalitis. 22 pts are evaluable for response (DLBCL 13, FL 7, MCL 2). Overall response rate (ORR) at 3 months is 68% (15/22): DLBCL 54% (7/13); FL 100% (7/7); MCL 50% (1/2). At the median follow-up 11.7 months, progression-free survival (PFS) from CTL019 infusion is 62% (DLBCL 43%; FL 100%). For responders at median follow up, response duration is 83% for DLBCL and 100% for FL. CONCLUSIONS: These results demonstrate that CTL019 cells can be prepared from extensively pretreated pts with active NHL and can induce durable responses with toxicity that is less than reported for chronic lymphocytic and acute lymphoblastic leukemias. Figure 1. Figure 1. Disclosures Schuster: Phamacyclics: Consultancy, Research Funding; Novartis: Research Funding; Gilead: Research Funding; Janssen: Research Funding; Nordic Nanovector: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Research Funding; Genentech: Consultancy; Hoffman-LaRoche: Research Funding. Svoboda:Seattle Genetics: Research Funding; Celgene: Research Funding; Celldex: Research Funding; Immunomedics: Research Funding. Dwivedy Nasta:BMS: Research Funding; Millenium Takeda: Research Funding. Porter:Genentech: Other: Spouse Employment; Novartis: Patents & Royalties, Research Funding. Mato:Celgene Corportation: Consultancy, Research Funding; Genentech: Consultancy; Pharmacylics: Consultancy, Research Funding; Pronai Pharmaceuticals: Research Funding; AbbVie: Consultancy, Research Funding; Janssen: Consultancy; TG Therapeutics: Research Funding; Gilead: Consultancy, Research Funding. Lacey:Novartis: Research Funding. Melenhorst:Novartis: Research Funding.…
Mosunetuzumab Demonstrates Durable Responses in Patients with Relapsed/Refractory Follicular Lymphoma and ≥2 Prior Therapies: Updated Analysis of a Pivotal Phase II Study
Hematological Oncology, Jun 1, 2023
Outcomes of diffuse large/high grade B cell lymphoma patients following receipt of autologous stem transplantation or chimeric antigen receptor‐modified T cells
Hematological Oncology, Jun 1, 2023
Combination of everolimus and itacitinib in patients with Hodgkin lymphoma relapsed/refractory to brentuximab vedotin (BV) and checkpoint inhibitors (CPI)
Hematological Oncology, Jun 1, 2023
Health‐related quality of life in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma treated with liso‐cel in TRANSCEND CLL 004
Hematological Oncology, Jun 1, 2023
Predictors of long‐term survival outcomes following receipt of autologous stem cell transplantation for patients with diffuse large/high grade B cell lymphoma
Hematological Oncology, Jun 1, 2023
Bendamustine Lymphodepletion Triggers Reduced Inflammatory Cytokines and Decreased Toxicities After Both 4‐1BB‐ and CD28‐COSTIMULATED CART19 for Non‐Hodgkin Lymphoma
Hematological Oncology, Jun 1, 2023
Erythropoietin: Physiologie Basis for Clinical Applications
Vox Sanguinis, 1993
Poster: IBCL-195: Primary Analysis of the Phase 2 ELARA Trial: Tisagenlecleucel Efficacy and Safety in Adult Patients with Relapsed/Refractory Follicular Lymphoma (r/r FL)
Clinical Lymphoma, Myeloma & Leukemia, Sep 1, 2021
Hematological Oncology, Jun 1, 2019
Introduction: T-cell directed therapies (e.g., CART , blinatumomab) are associated with significa... more Introduction: T-cell directed therapies (e.g., CART , blinatumomab) are associated with significant risk of Grade (Gr) ≥3 neurotoxicity and CRS/infusion-related reaction (IRR). Mosunetuzumab is a CD20/CD3 bispecific antibody that directs T-cells to engage and eliminate malignant B-cells. We report safety results from an ongoing Phase 1/1b study (NCT02500407) of mosunetuzumab in patients (pts) with R/R B-cell NHL. Methods: Pts received ascending doses on Day 1, Day 8, and Day 15 of Cycle 1 (step-up dosing), then a fixed dose on Day 1 of every 21-day cycle thereafter, up to a maximum of 17 cycles. Primary outcome measures included safety and efficacy. Results: As of October 23, 2018, 114 pts who received step-up dosing of mosunetuzumab were evaluable for safety (Table). The majority of adverse events (AE) occurred during Cycle 1 and 2. Neurologic AEs (NAE), defined from Nervous System or Psychiatric System Organ Classes, were mostly low grade, transient (median duration 4 days) and reversible; most common ones were headache (14%) and T A B L E 1 Safety Pts, n (%) n=114 [Max dose: 20 mg] ≥1 AE 109 (96) Gr ≥3 AEs; drug-related 68 (60); 33 (29) Serious AE*; drug-related 34 (30), 15 (13) NAE 50 (44) Gr 1-2 46 (40) Gr 3 4 (4) CRS/IRR 29 (25) Gr 1-2 28 (25) Gr 3 1 (1) *excluding progressive disease 310 ABSTRACT dizziness (8%). Gr ≥3 NAEs occurred in 4 pts (4%) with only 1 treatment-related event (hepatic encephalopathy). CRS/IRR was reported in 25% of pts, with only 1 Gr 3 event. Most common CRS symptoms were pyrexia (86%), chills (38%), and tachycardia and headache (14% each). There were no Gr 5 events related to CRS or NAEs. No apparent dose toxicity relationship was observed with step-up dosing in these pts, despite escalation of the Cycle 1 Day 15 dose to 20 mg, consistent with observed peak IL-6 levels after a low Cycle 1 Day 1 dose. In these pts, objective responses were observed in 24/73 (33%; complete response [CR], 13 [18%]) aggressive NHL and 17/32 (53%; CR, 10 [31%]) indolent NHL pts. Conclusions: Step-up dosing has enabled continued dose escalation of mosunetuzumab with no apparent increases in toxicity, exhibiting a promising risk-benefit profile. Acknowledgement: This work was funded by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance, under the direction of Laurie Sehn, was provided by Louise Profit and Russell Craddock of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd.
IBCL-195: Primary Analysis of the Phase 2 ELARA Trial: Tisagenlecleucel Efficacy and Safety in Adult Patients with Relapsed/Refractory Follicular Lymphoma (r/r FL)
Clinical Lymphoma, Myeloma & Leukemia, Sep 1, 2021
Context Tisagenlecleucel demonstrated durable responses and manageable safety in adult patients w... more Context Tisagenlecleucel demonstrated durable responses and manageable safety in adult patients with r/r diffuse large B-cell lymphoma. Objective Determine the efficacy and safety of tisagenlecleucel in adult patients with r/r FL. Design ELARA (NCT03568461) is an international, multicenter, single-arm, phase 2 trial of tisagenlecleucel treatment. Patients or Other Participants Adult (≥18 years) patients with r/r FL (grades 1–3A) after ≥2 lines of therapy or whose disease relapsed after autologous stem cell transplant were eligible. As of September 28, 2020, 98 patients were enrolled. Interventions Bridging therapy was permitted, and disease status was reassessed prior to infusion. Patients received tisagenlecleucel (0.6–6×10 8 CAR+ viable T-cells) after lymphodepleting chemotherapy. Main Outcomes Measures Primary endpoint was complete response rate (CRR) by central review (Lugano 2014 criteria). Secondary endpoints included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, and cellular kinetics. Results Ninety-seven patients received tisagenlecleucel (median follow-up, 10.6 months). Median age at study entry was 57 years (range, 29-73), 85% had stage III–IV disease, 60% had a FLIPI score ≥3, 65% had bulky disease, and 42% had LDH > upper limit of normal. Median number of prior therapies was 4 (range, 2–13); 78% of patients were refractory to their last treatment, and 60% progressed ≤2 years of initial anti-CD20-containing treatment. Among 94 patients evaluable for efficacy, CRR was 66% (95% CI, 56%–75%), and ORR was 86% (95% CI, 78%–92%). Estimated DOR (CR) and PFS rates at 6 months were 94% (95% CI, 82%–98%) and 76% (95% CI, 65%–84%), respectively. Of 97 patients evaluable for safety, 65% experienced grade ≥3 adverse events ≤8 weeks post-infusion, most commonly neutropenia (28%) and anemia (13%). Any-grade cytokine release syndrome (Lee scale) occurred in 49% of patients. Any-grade neurological events (per CTCAE v4.03) occurred in 9% of patients. Three patients died from disease progression. C(max) and AUC(0–28d) for tisagenlecleucel were similar between responders and nonresponders. C(max) was achieved at a median of 10 days in responders and 12.9 days in nonresponders. Conclusions Tisagenlecleucel demonstrated efficacy and a favorable safety profile in patients with r/r FL. The study was funded by Novartis.
Population Pharmacokinetic Model Identifies an Optimal Fludarabine Exposure for Improved Outcomes after CD19-Directed CAR T Cell Therapy for Aggressive B-NHL: Analysis from the Cell Therapy Consortium
Blood, Nov 15, 2022
Multi-Institutional Review of Bridging Radiotherapy Prior to Chimeric Antigen Receptor T-Cell Therapy for B-Cell Lymphomas
Blood, Nov 15, 2022
Racial, age, and sex disparities in chronic lymphocytic leukemia (CLL) patients treated with novel therapies
Journal of Clinical Oncology, May 20, 2018
6577Background: Differences in outcomes have been reported in CLL pts receiving chemo±immunothera... more 6577Background: Differences in outcomes have been reported in CLL pts receiving chemo±immunotherapy with non-Caucasians and males having inferior outcomes. Less is known if such disparities exist f...
Choosing First-Line Therapy for Follicular Lymphoma (FL): A Decision Analysis
Blood, Nov 16, 2008
Introduction: There is no standard of care for first-line therapy of low-grade FL. In US practice... more Introduction: There is no standard of care for first-line therapy of low-grade FL. In US practice, the most common strategy is rituximab with combination chemotherapy. However, the optimal choice of regimen remains controversial; options include RCVP, RCHOP and R-Fludarabine-based chemotherapy (RFlu). Because data from randomized clinical trials are not available and unlikely to be generated in the future, we performed a decision analysis comparing RCVP, RCHOP, and RFlu as first-line therapy for FL. Methods: We constructed a Markov model of sequential first- and second-line therapy based on prescribing patterns in the US. The endpoint of the model was quality-adjusted time to tertiary referral for therapy such as RIT or autologous transplant (≥3rd line). A literature review was performed of the Medline database and international meeting abstracts. Clinical trials of both untreated and previously treated patients were systematically evaluated using explicit eligibility criteria. Data were extracted regarding response rates, treatment-related mortality, and progression-free survival (PFS). Weighted estimates were obtained using a fixed effects meta-analysis. The model also incorporated published data on heath state utilities, risk of anthracycline cardiotoxicity and fludarabine-related delayed cytopenias. Primary and sensitivity analyses were performed using TreeAge software. Results: The optimal treatment strategy consisted of RCHOP in first-line followed by RFlu in second-line (9.0 quality-adjusted life years; QALYs). Strategies containing RCVP in either first- or second-line were inferior (6.2–7.7 QALYs). The model was sensitive to first-line PFS of RCHOP and RFlu when these were varied over the range of estimates obtained from individual published trials. The model was robust in sensitivity analysis of most other parameters, including rate of delayed cytopenias after RFlu, anthracycline cardiotoxicity, and quality of life adjustments. Conclusions: Using decision analysis, the optimal first-line therapy for low-grade FL is RCHOP, followed by RFlu in second-line. This strategy maximizes quality-adjusted time to tertiary therapy. Use of RCVP does not improve overall quality-adjusted time relative to more intensive therapies.
Impact of FDG-PET Imaging Versus Conventional Staging Modalities on Staging and Treatment Decisions in Large B-Cell, Follicular, and Hodgkin’s Lymphomas
Blood, Nov 16, 2004
Clinical staging of lymphomas has a critical role in determining appropriate therapy and in thera... more Clinical staging of lymphomas has a critical role in determining appropriate therapy and in therapeutic response assessment. While anatomic imaging by CT or MRI, together with physical examination and bone marrow biopsy (conventional staging modalities or CSM), have historically provided the basis for staging and response assessment, positron emission tomography using 18-fluoro-2-deoxyglucose (FDG-PET) has increasingly been employed in the management of patients (pts) with lymphomas. Studies comparing FDG-PET with anatomic imaging have generally found that FDG-PET identifies more sites of disease; however, the impact of FDG-PET imaging on assignment of clinical stage and treatment decisions is unclear. We retrospectively examined the impact of FDG-PET imaging on assignment of disease stage and treatment decisions compared with CSM alone in 91 pts with large B-cell lymphoma (LBCL; n=30), follicular lymphoma (FL; n=29) and Hodgkin’s lymphoma (HL; n=32). 25/30 LBCL (83%), 26/32 HD (81%) and 17/29 FL pts (59%) were evaluated at initial diagnosis by FDG-PET imaging and CSM, while others were evaluated during subsequent relapse. FDG-PET and CSM defined the same stage in 69/91 pts (76%). Stage assignment was most concordant in LBCL with only 5/30 (17%) of cases having different stages, while stage assignments were discrepant in 7/32 (22%) of cases of HL and in 10/29 (34%) of cases of FL. Of the 22 pts with discrepant results, FDG-PET resulted in upstaging of disease in 11 pts and downstaging in 11 pts. Independent confirmatory tests resolving the discrepancy were obtained in 3 of 11 pts upstaged (27%) and 7 of 11 pts downstaged by FDG-PET (64%). Abnormal FDG uptake in lymph nodes accounted for all cases upstaged by FDG-PET in which no confirmatory test was available (8/8 pts). Among 10 cases resolved by biopsy, discrepant sites included bone marrow (n = 4), bone (n = 1), pelvic or abdominal structures (n = 3), and lymph nodes (n = 2). FDG-PET results were true positive in 2/10, true negative in 1/10, false positive in 1/10, and false negative in 6/10 cases (including 4 cases with BM involvement). Incorporation of FDG-PET led to treatment changes in a minority of patients (2%). We conclude that FDG-PET is an efficient single imaging modality in pts with LBCL, FL and HL, providing information complementary to CSM. However, changes in treatment based on FDG-PET results are rare. Discrepancies between FDG-PET and CSM should be resolved by biopsy when feasible, particularly in cases in which treatment would be altered.
Immunogenicity of tisagenlecleucel in relapsed/ refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL) patients
Journal of Clinical Oncology, May 20, 2018
3044Background: Tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell therapy, contains a mu... more 3044Background: Tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell therapy, contains a murine single chain variable fragment (mCAR19) binding domain. Humoral immunity to anti-mCAR19 had no ...
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Papers by Stephen Schuster