scholarly journals The Profiling of Circulating Tumor DNA in Pediatric Mature B-Cell Non-Hodgkin Lymphoma（B-NHL）: A Multicenter and Prospective Clinical Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2400-2400
Author(s):  
Juan Wang ◽  
Haixia Guo ◽  
Cai Yun ◽  
Huiqin Chen ◽  
Liangchun Yang ◽  
...  
Keyword(s):  
B Cell ◽  
Allele Frequency ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Sample Type ◽  
Plasma Samples ◽  
Tumor Residue ◽  
Pet Ct ◽  
Risk Patients

Abstract Background Next-generation sequencing (NGS) based on liquid biopsy has been an emerging technology to identify tumor-specific genetic aberrations in adult lymphoma. However, there were few studies on the genomic profiling of plasma circulating tumor-derived DNA (ctDNA) in pediatric mature B-NHL. Methods Paraffin-embedded tissue (FFPE) and plasma samples from the newly diagnosed patients were collected and sequenced by 475 genes panel before, during and post of treatment. Clinical stage system, risk stratification and treatment of pediatric mature B-NHL followed a the modified BFM-95 protocol. Results A total of 53 pediatric mature B-NHLs were enrolled，including 35 Burkitt lymphoma, 18 diffused large B cell lymphoma/high-grade B cell lymphoma (DLBCL/HGBCL). We collected 38 tissue and 124 plasma samples for somatic mutation testing. The number of somatic mutations and the TOP 5 genes detected in the 38 tissues and 31 baseline plasma samples, were 416 vs 496, and MYC(71%), DDX3X(45%)，ID3 (42%), TP53(40%), SMARCA4(29%) (Fig1. A)vs MYC(52%), DDX3X(45%)，ID3(42%), TP53(36%), GNA13(23%) (Fig1. B), respectively. The median allele frequency of mutations in plasma was 3%(ranged from 0.2% to 96.6%) and MYC, DDX3X, ID3, TP53, SMARCA4,ARID1A shows higher max somatic allele frequency (MSAF), indicated that was the early events in tumor genesis. The sensitivity of plasma ctDNA to detecting tissue mutations was 63.4% in the 19 matched samples (11 samples from BL and 8 samples from DLBCL/HGBCL) and the sensitivity in BL and DLBCL/HGBCL were 64.1% and 62%, respectively. All genomic alteration types, including single nucleotide variants (SNVs), indels, and gene fusions were detected in similar proportions in each sample type and the gene mutation rate of every gene detected in paired tissue and ctDNA samples. Among the 37 mature B-NHL patients, 6 patients were collected plasma samples after resection of tumor, of which 4 patients was not detected the somatic gene mutations in plasma (Fig. 2). The abundance of ctDNA in patients with stage IV (N=10) was significantly higher than that of stage I-II (N=6) (P=0.0002) and stage III patients(N=15)(P<0.0001)(Fig3. A). Similarly the abundance of ctDNA mutations in high risk patients(N =11)was significantly higher than that of low risk patients (N=8)(P<0.0001) and Medium risk patients (N=12) (P<0.0001) (Fig3. B). MSAF of ctDNA mutations was significantly correlated with LDH and the abundance of ctDNA mutations (P<0.0001) (Fig3. C,D). With a median follow-up of 182 Days, 33 patients have completed anti-tumor treatment, 27 patients completed post-treatment PET-CT, and 20 patients have done ctDNA testing synchronously. PET-CT showed tumor residue in 4 patients, of which 2 patients showed no tumor residue in pathology and ctDNA, 1 patient showed tumor residue in pathology but not in ctDNA and with tumor progression 6 months after treatment, 1 patient unable to take biopsy showed no tumor residue in ctDNA and was no tumor reccourence with regular follow-up. At the last follow-up, 1 patient was disease progression, and all of the 53 patients survived. Conclusion Plasma ctDNA testing by NGS was practicable in pediatric mature B-NHL. The abundance of ctDNA is significantly related to tumor burden. CtDNA testing may be more sensitive than PET-CT for residual disease assessment. Nevertheless, sample size expansion is required to verify such conclusions. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Surveillance PET-CT Scanning Is Useful in the First 18 Months Following Completion of Therapy for Patients with Diffuse Large B-Cell Lymphoma with IPI≥3.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2652-2652
Author(s):  
Chan Y Cheah ◽  
Michael S Hofman ◽  
Michael J. Dickinson ◽  
Andrew Wirth ◽  
David A Westerman ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
High Sensitivity ◽  
B Cell Lymphoma ◽  
Ct Scanning ◽  
Primary Therapy ◽  
Large B Cell Lymphoma ◽  
Pet Ct ◽  
Large B Cell

Abstract Abstract 2652 Introduction Despite improvements in cure rates for patients with diffuse large B-cell lymphoma (DLBCL), up to 40% relapse after achieving initial remission, mostly within 18 months from treatment. There is no consensus as to role, or most appropriate form of post-remission surveillance. Our aim was to explore the role of Positron Emission Tomography combined with computer tomography (PET-CT) scanning in the follow up of patients with diffuse large B-cell lymphoma (DLBCL) achieving complete metabolic response (CMR) after primary therapy, identify patterns of relapse and define a risk-adapted strategy. Results We included 116 patients with de novo DLBCL treated at our centre between 2002 and 2009 with a negative post-treatment PET-CT, and at least one surveillance PET-CT scan. International Prognostic Index (IPI) was <3 in 77 (66%) and ≥3 in 37 (32%) patients. With a median follow up of 53 months (range 8–133), 456 surveillance scans were performed (range 1–10 per patient). 13 patients (11%) relapsed, with an actuarial 5 year relapse free survival of 86%. Two-thirds of relapses occurred in the first 18 months following completion of treatment. In seven cases (54%), the relapse was suspected based on symptoms and in six (46%) the relapse was subclinical and detected with PET. There was no difference in survival (P=0.76) or second line IPI (P=1.00) between the groups, as the number of relapses was small. PET-CT had very high sensitivity (100%), specificity (98%) and negative predictive value (NPV, 100%) with positive predictive value (PPV) 56% in the cohort of patients with a low IPI (<3) compared with 80% if the IPI was ≥3. Across the entire cohort, the average number of patients in remission needed to scan to detect one subclinical relapse within the first 18 months was 42. However, for those with an IPI ≥3 the number needed to scan to detect one subclinical relapse was 22. Surveillance PET-CT had a very low yield after 18 months had elapsed from the conclusion of primary therapy (1 true positive among 170 scans). Interim response PET-CT was performed in 81 (70%) patients; achieving CMR was not a predictor of time to relapse (P=0.65) or having a positive surveillance scan, irrespective of IPI (P=1.00). Second malignancies were detected by PET-CT in eight patients (7%). Conclusion The achievement of CMR at the completion of primary therapy identifies a group of patients with favourable outlook and a low risk of relapse. Surveillance PET-CT scanning within this select cohort has high sensitivity, specificity and NPV and despite the low number of relapses retains a high PPV, particularly in patients with IPI≥3. Surveillance PET-CT is useful in the first 18 months following completion of primary therapy in patients in whom IPI at diagnosis is ≥3. We feel that such a strategy would be appropriate to evaluate in a prospective comparative trial. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Potential Utility of Circulating Tumor DNA Monitoring in Primary Mediastinal B-Cell Lymphoma Treated with R-DA-EPOCH

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4491-4491
Author(s):  
Ana Jimenez-Ubieto ◽  
María Poza ◽  
Alejandro Martín-Muñoz ◽  
Sara Dorado ◽  
Yanira Heredia ◽  
...  
Keyword(s):  
B Cell ◽  
Somatic Mutations ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Circulating Tumor Dna ◽  
Plasma Samples ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Pet Ct ◽  
Tumor Dna

Abstract Background: Primary mediastinal B-cell lymphoma (PMBCL) is a rare subtype of aggressive B-cell lymphoma. Most relapses occur within the first few months resulting in a dismal prognosis; therefore, it's important to identify primary chemorefractory patients at an early stage, to improve their prognosis. Our group have demonstrated that Circulating Tumor DNA (ctDNA) detected by deep sequencing (DeepSeq) constitute a new non-invasive marker for monitoring response in follicular lymphoma (Jimenez-Ubieto A. et al. ASH 2020). CtDNA monitoring in PMBCL might help to better assess therapeutic response, correct false positive PET/CT results due to residual uptake of the mediastinum and define patients who will benefit from radiation therapy (RT). Here we analyzed the potential value of ctDNA monitoring in 11 PMBCL treated with R-DA-EPOCH between 2018-2020 in the Hospital 12 de Octubre. Methods: Genomic DNA from paraffin embedded (FFPE) lymph node biopsies were obtained from 11 PMBCL cases at diagnosis. Samples were sequenced with a short length Ampliseq Custom Panel (Thermo-Fisher) designed to cover all coding regions of 56 lymphoma specific genes with an average depth of 700x. After annotation and filtering, 5-8 somatic mutations previously described in lymphoma were selected to be screened in plasma samples. The plasma derived cfDNA was obtained from 8-16mL of peripheral blood collected in EDTA tubes and processed in less than 4h by column purification (QIAamp Circulating Nucleic Acid Kit, Qiagen). A total of 31 different plasma time-points were sequenced in triplicates. On average 78ng (9-224 ng) of cfDNA was used for the DeepSeq of the specific mutations selected in each patient. An average coverage of 236.000x per triplicate was obtained for each mutation. The detection cut-off of 1E-4 was defined based on the LOD obtained in healthy controls donors. 18F-fluorodeoxyglucose (FDG) PET/CT scans were performed on a General Electric Discovery MI Scanner at basal, interim (after 4 cycles), end of induction (EOI) and after radiotherapy (RT). Results: The median age was 33 years and 63.6% were female. Most cases (81.8%) were diagnosed with stage I or II disease and 27.3% cases present with extranodal involvement. On interim PET, 4 patients reached Complete response (CR) and 7 Partial Response (PR, DS4). At EOI, the number of CR turned to 6/11 (55%). All patients in PR at EOI (n=5) and two patients in CR (DS3) with residual mass received RT consolidation (median dose 32Gy). After RT the rate of CR was 91% (10/11). One patient progressed to a classical Hodgkin lymphoma (cHL). None of the patients in CR have relapsed after a median follow-up of 22 months. One patient died due to a mediastinal synovial sarcoma. A total of 125 somatic mutations were detected in the 11 baseline samples with a median of 8 per patient (rank 5-35). The three most frequently mutated genes were SOCS1 (73%), B2M (55%) and TNFAIP3 (46%). Despite the reduced size of our cohort, the mutational frequencies were comparable to the described by Mottok A. et al (Blood 2018, Figure 1A). The DeepSeq of six diagnosis plasma samples showed a lower Variant Read Frequency (VRF) in cfDNA. On those paired samples, 25/28 mutations were detected in plasma, with a median VRF of 2% (0-53%) vs 24% (5.5%-87%) in Lymph nodes (Figure 1B). The rest of the plasma samples corresponded to 1st cycle (n=5), 4th cycle (n=6), EOI (n=7) and after RT (n=5). After 1 cycle of chemotherapy 3/4 patients who reached CR at EOI had already undetectable ctDNA (Figure 1C). One patient with positive ctDNA after 1 cycle needed RT to convert to CR. All the CR evaluations by PET-TC who had available ctDNA data, presented undetectable ctDNA (n=9). In the EOI analysis all+ patients except the one who progressed to cHL had undetectable ctDNA. In the PR interim evaluations 2/5 had undetectable ctDNA and converted to CR at EOI. Of the three patients with detectable ctDNA, one progressed to cHL (Figure 1D) and 2 needed RT to convert to CR. Conclusions: Our results demonstrate that disease monitoring using DeepSeq of plasma ctDNA is feasible in PMBCL. Regarding prediction of relapse, the positive predictive value of ctDNA was 100%. An early ctDNA analysis (even after only one R-DA-EPOCH cycle) was able to predict patients in need of RT. Despite the DeepSeq of ctDNA could be useful to disease monitoring to prevent relapse and toxicity reduction by selecting cases in need of RT, more patients are necessary to draw meaningful conclusions. Figure 1 Figure 1. Disclosures Martín-Muñoz: Altum sequencing: Current Employment. Dorado: Altum sequencing: Current Employment. Heredia: Altum sequencing: Current Employment, Current equity holder in publicly-traded company. Rufian: Altum sequencing: Current Employment. Canales: Incyte: Consultancy; iQone: Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Sanofi: Consultancy; Eusa Pharma: Consultancy, Honoraria; Sandoz: Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Speakers Bureau; Gilead/Kite: Consultancy, Honoraria. Juarez: Altum sequencing: Current Employment. Sanchez: Altum sequencing: Current Employment. López-Muñoz: Amgen: Consultancy. Ayala: Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Honoraria; Celgene: Honoraria. Martínez-López: Janssen, BMS, Novartis, Incyte, Roche, GSK, Pfizer: Consultancy; Roche, Novartis, Incyte, Astellas, BMS: Research Funding. Barrio: Altum sequencing: Current Employment, Current equity holder in publicly-traded company.

Clinical usefulness of PET/CT in initial staging and response evaluation of primary gastric lymphoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19541-e19541
Author(s):  
J. Yi ◽  
S. Kim ◽  
S. Lee ◽  
S. Park ◽  
Y. Ko ◽  
...  
Keyword(s):  
Ct Scan ◽  
B Cell ◽  
Cell Lymphoma ◽  
Gastric Lymphoma ◽  
B Cell Lymphoma ◽  
Ct Scans ◽  
Primary Gastric Lymphoma ◽  
Pet Ct ◽  
Pet Ct Scan

e19541 Background: Positron emission tomography (PET)/computed tomography (CT) scan has a well-established role in the management of non-Hodgkin's lymphoma (NHL). However, in case of the primary gastric lymphoma, which is the most frequent extranodal NHL, the role of PET/CT scan is still controversial. Methods: We retrospectively analyzed 42 patients with primary gastric lymphoma who underwent PET/CT scans; 32 patients with diffuse large B-cell lymphoma (DLBCL) and 10 patients with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) were analyzed. The PET/CT scans were compared with clinicopathologic features and the results of CT and endoscopy. After corresponding treatment, response was evaluated by conventional CT scans or PET/CT scans and endoscopy with biopsy Results: Nine patients were up-staged based on the results of their PET/CT scan compared to CT (7 DLBCL, 2 MALT lymphomas) while six patients were down-staged by the PET/CT scan. The high SUVmax group, defined as SUVmax ≥ median value, was significantly associated with an advanced Lugano stage (P < 0.001). Three patients with DLBCL, who showed an initially high SUVmax, died of disease progression. Although not statistically significant, there was a tendency of inferior outcome in the group with high SUVmax. Among 24 patients for whom follow-up PET/CT scan with endoscopy was performed, 11 patients with ulcerative or mucosal lesions showed residual FDG uptake. All of these gastric lesions were grossly and pathologically benign lesions without evidence of lymphoma cells. Conclusions: PET/CT scan can help staging patients with primary gastric lymphoma, and the maximum SUV has possibility to have prognostic value. However, the residual FDG uptake observed during follow-up should be interpreted cautiously in association with the results of endoscopy and multiple gastric biopsies. No significant financial relationships to disclose.

scholarly journals Assessment of Cell-Free DNA (cfDNA) in 221 Patients with Lymphoproliferative Malignancies at Diagnosis and during Follow-up

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 492-492 ◽  
Author(s):  
Marcio M Andrade-Campos ◽  
Antonio Salar ◽  
Blanca Sanchez-Gonzalez ◽  
Concepción Fernández-Rodríguez ◽  
Eva Gimeno ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Plasma Samples ◽  
Cell Free Dna ◽  
Free Dna ◽  
The Mean ◽  
Post Therapy

Background:The isolation of cell-free DNA (cfDNA) evolved the concept of liquid biopsy. Several works have analyzed the presence of cfDNA in lymphomas, especially in diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL), however there is limited information regarding the detection of cfDNA in other types of lymphomas or the role of cfDNA detection to monitor disease outcome. Objectives:1.- To analyze the presence of cfDNA at diagnosis of patients with lymphoproliferative malignancies. 2.- To evaluate the change in concentration of cfDNA ([cfDNA]) after treatment in DLBCL patients. Material and Methods:A retrospective study in a single center was performed including 221 adult patients since January 2015 to February 2019 with: DLBCL, HL, marginal zone lymphoma (MZL), follicular lymphoma (FL), chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), lymphoplasmacytic lymphoma (LPL) and peripheral T-cell lymphomas (TCL). All patients had plasma samples collected at diagnosis that were stored in the institutional biobank (MarBiobank). The cfDNA were obtained from 1 mL of -80°C frozen stored plasma using the MagMax Cell Free DNA isolation kit (Thermo Fisher Scientific). The cfDNA quantification was performed using the Qubit system with the dsDNA high sensitivitykit (Thermo Fisher) and is expressed as ng/mL of plasma. In addition, patients with DLBCL who were treated with rituximab-CHOP/CHOP-like regimens were evaluated for [cfDNA] analysis, pre and post-treatment, and results were compared with PET-CT scan findings. Results: Stored plasma samples at diagnosis were available in 221 patients: DLBCL 82, HL 22, CLL/LPL 13, FL 36, MZL 37, MCL: 11, TCL 10 and others 10 (B-cell lymphoma unclassified, hairy cell leukemia, Burkitt lymphoma). Successful identification of cfDNA was obtained in 95.9% (212/221) of samples. DLBCL patients showed higher [cfDNA] globally and, DLBCL, HL and FL patients showed a higher concentration than MZL who exhibited the lower concentration of all groups (p=0.009; p=0.013 and p=0.002); see table 1. 50 DLBCL patients with a median follow-up since diagnosis of 25.5 (5-51) months were analyzed. Median age was 67 (19-79) years, males 56% (28). IPI distribution: low-risk 28% (14), low-intermediate 26% (13), high-intermediate 24% (12) and high risk 22% (11) cases. Detection of cfDNA was successful in 100% at diagnosis and in 98% (49) cases post-therapy. The mean [cfDNA] at diagnosis was 2.21 (standard deviation- SD: 1.60) ng/mL with a correlation with LDH concentration (p&lt;0.001) and with high-risk IPI category (p=0.02). The mean [cfDNA] in the post-therapy sample was 4.39 (SD 16.46) ng/mL. After therapy 86% (43) of patients achieved at least PR (41 complete response), and the mean [cfDNA] for these patients was 1.58 (SD 1.96); patients who showed no response or progressive disease after therapy exhibited higher [cfDNA] 21.25 ng/mL (SD 41.91)(p&lt;0.001). In order to evaluate the clinical relevance of the changes of [cfDNA] after treatment, we considered a variation of +/-25% of [cfDNA at diagnosis] regarding [cfDNA after therapy] to classify the results. Therefore, 13 patients had an increase of [cfDNA after therapy], 6 patients had no change, and 31 patients had a decrease. Patients with a decrease in [cfDNA] at the end of therapy were less likely to relapse (p&lt;0.01) During follow-up, two patients relapsed after 24 and 8 months. The patient who relapsed after 24 months showed an increase in [cfDNA], from 0.966 ng/mL to 20.80ng/mL three months before the histological confirmation of relapse. Conclusions:Isolation of cfDNA was feasible in &gt;95% of lymphoma patients independently of histology or disease stage. Patients with DLBCL exhibited the higher cfDNA concentration which were also correlated with LDH concentrations and high-risk IPI. Kinetics of [cfDNA] is related to response to therapy in DLBCL and also might detect relapse. Even though additional studies are necessary, monitoring of cfDNA may help in management of patients with DLBCL. Disclosures Salar: Roche: Research Funding, Speakers Bureau; Janssen Pharmaceuticals: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Celgene: Consultancy. Sanchez-Gonzalez:Takeda: Consultancy, Speakers Bureau; Alexion: Speakers Bureau; Gilead: Speakers Bureau; Shire: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Gimeno:JANSSEN: Consultancy, Speakers Bureau; Abbvie: Speakers Bureau. Bellosillo:Qiagen: Consultancy, Speakers Bureau; TermoFisher Scientific: Consultancy, Speakers Bureau.

End-of-treatment 18F-FDG PET/CT in diffuse large B cell lymphoma patients: ΔSUV outperforms Deauville score

2021 ◽  
pp. 1-9
Author(s):  
François Allioux ◽  
Damaj Gandhi ◽  
Jean-Pierre Vilque ◽  
Cathy Nganoa ◽  
Anne-Claire Gac ◽  
...  
Keyword(s):  
B Cell ◽  
Fdg Pet ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
End Of Treatment ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct ◽  
Large B Cell

scholarly journals Long-Term Follow-Up of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy

2020 ◽  
Vol 38 (32) ◽  
pp. 3805-3815
Author(s):  
Kathryn M. Cappell ◽  
Richard M. Sherry ◽  
James C. Yang ◽  
Stephanie L. Goff ◽  
Danielle A. Vanasse ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T

PURPOSE Anti-CD19 chimeric antigen receptors (CARs) are artificial fusion proteins that cause CD19-specific T-cell activation. Durability of remissions and incidence of long-term adverse events are critical factors determining the utility of anti-CD19 CAR T-cell therapy, but long-term follow-up of patients treated with anti-CD19 CAR T cells is limited. This work provides the longest follow-up of patients in remission after anti-CD19 CAR T-cell therapy. METHODS Between 2009 and 2015, we administered 46 CAR T-cell treatments to 43 patients (ClinicalTrials.gov identifier: NCT00924326 ). Patients had relapsed B-cell malignancies of the following types: diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma (DLBCL/PMBCL; n = 28), low-grade B-cell lymphoma (n = 8), or chronic lymphocytic leukemia (CLL; n = 7). This report focuses on long-term outcomes of these patients. The CAR used was FMC63-28Z; axicabtagene ciloleucel uses the same CAR. Cyclophosphamide plus fludarabine conditioning chemotherapy was administered before CAR T cells. RESULTS The percentages of CAR T-cell treatments resulting in a > 3-year duration of response (DOR) were 51% (95% CI, 35% to 67%) for all evaluable treatments, 48% (95% CI, 28% to 69%) for DLBCL/PMBCL, 63% (95% CI, 25% to 92%) for low-grade lymphoma, and 50% (95% CI, 16% to 84%) for CLL. The median event-free survival of all 45 evaluable treatments was 55 months. Long-term adverse effects were rare, except for B-cell depletion and hypogammaglobulinemia. Median peak blood CAR-positive cell levels were higher among patients with a DOR of > 3 years (98/µL; range, 9-1,217/µL) than among patients with a DOR of < 3 years (18/µL; range, 0-308/μL, P = .0051). CONCLUSION Complete remissions of a variety of B-cell malignancies lasting ≥ 3 years occurred after 51% of evaluable anti-CD19 CAR T-cell treatments. Remissions of up to 9 years are ongoing. Late adverse events were rare.

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