scholarly journals Safety of allogeneic hematopoietic cell transplant in adults after CD19-targeted CAR T-cell therapy

2019 ◽  
Vol 3 (20) ◽  
pp. 3062-3069 ◽  
Author(s):  
Mazyar Shadman ◽  
Jordan Gauthier ◽  
Kevin A. Hay ◽  
Jenna M. Voutsinas ◽  
Filippo Milano ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Therapy ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
T Cell Therapy ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Car T Cell Therapy ◽  
Key Points ◽  
Car T ◽  
Risk Patients

Key Points The toxicity of allo-HCT in patients with prior CAR-T therapy was not higher than what is expected in these high-risk patients. In ALL patients, there seems to be a benefit from earlier utilization of allo-HCT after CAR-T therapy.

scholarly journals Viral Kinetics and Outcomes of Adenovirus Reactivation Following Allogeneic Hematopoietic Cell Transplant or CAR-T Cell Therapy

2020 ◽  
Vol 26 (3) ◽  
pp. S331
Author(s):  
Aditya Aniruddha Chandorkar ◽  
Anthony D. Anderson ◽  
Michele I. Morris ◽  
Yoichiro Natori ◽  
Krishna V. Komanduri ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Viral Kinetics ◽  
T Cell Therapy ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Car T Cell Therapy ◽  
Car T

137 Genomics of multiple myeloma influences the expression of CAR T-cell targets

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A150-A150
Author(s):  
Christina Yu ◽  
Brian Walker ◽  
G David Roodman ◽  
Kun Huang ◽  
Michel Sadelain ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cell ◽  
High Risk ◽  
Cell Surface ◽  
T Cell Therapy ◽  
Genomic Features ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Risk Patients

BackgroundMultiple Myeloma (MM) is an incurable disease, with a particularly poor prognosis for patients with refractory/relapsed MM or high-risk cytogenetics. Chimeric Antigen Receptor (CAR) T-cell therapy targeting BCMA can induce deep responses in highly pretreated RRMM; however, remissions are not sustained, and the majority of patients eventually relapse. We hypothesized that genomic determinants of MM play a role in dictating the expression of surface targets that can be of use for immune targeting.MethodsWe analyzed the gene expression of 24 immunotherapeutic targets in a combined dataset of 1900 MM patients from three independent expression datasets obtained from the Multiple Myeloma Research Foundation CoMMpass study and Gene Expression Omnibus. Given that CAR T-cell therapy may be especially important for patients with high-risk myeloma, we defined the expression of each target in high-risk MM patients by stratifying patients based on several genomic features impacting prognosis. Additionally, we conducted a gene co-expression network analysis and identified 30 gene modules highly correlated with 16 cell surface targets from our panel, further suggesting that genetic determinants of MM may shape a targetable cell surfaceome. In order to determine whether targeting any of these candidate antigens might cause major toxicity to normal cells, we utilized several repositories providing protein data1 to annotate their expression in several normal cell types.ResultsWe determined that a number of genomic factors could stratify the 24 targets into three general groups: 1) targets that show consistent overexpression in high-risk patients: IGF1R, ITGB7, GPRC5D and CD70, and are thus suitable for most high-risk patients; 2) targets that are down-regulated in patients with high-risk genomic features: CD200, CD19, CD40, CD1D and IGKC, perhaps playing a role in cancer immune escape; and 3) targets associated with one specific genetic abnormality, i.e. t(4;14): FUT3, SLAMF7, CD56, CD138 and BCMA, thus of use for precision CAR therapy in this high-risk patient subset.ConclusionsOur work provides a means of target selection for precision CAR therapy, by considering both patient genomic backgrounds and cancer cell surface profiles. Furthermore, our results provide a roadmap for immunotherapy of MM by unbiasedly comparing the expression of top MM cell surface targets in patient data and normal cells and suggest that the genetic landscape of MM may predict the expression of specific targets for precision immunotherapy. The quest for novel MM targets for immunotherapies remains open, and CAR target discovery driven by specific genetic events remains an active area of investigation.ReferencePerna F, Berman SH, Soni RK, et al. Integrating proteomics and transcriptomics for systematic combinatorial chimeric antigen receptor therapy of AML. Cancer Cell 2017;32(4):506–19.

scholarly journals Long-term remission in multiply relapsed enteropathy-associated T-cell lymphoma following CD30 CAR T-cell therapy

2020 ◽  
Vol 4 (23) ◽  
pp. 5925-5928
Author(s):  
Timothy J. Voorhees ◽  
Nilanjan Ghosh ◽  
Natalie Grover ◽  
Jared Block ◽  
Catherine Cheng ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Key Points ◽  
Car T

Key Points CD30 CAR T-cell therapy promoted a prolonged remission in a patient with multiply relapsed EATL.

scholarly journals Safety and efficacy of CAR T cells in a patient with lymphoma and a coexisting autoimmune neuropathy

2020 ◽  
Vol 4 (23) ◽  
pp. 6019-6022
Author(s):  
Khushali S. Jhaveri ◽  
Ilana Schlam ◽  
Noa G. Holtzman ◽  
Monica Peravali ◽  
Perry K. Richardson ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Dlbcl Patient ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Key Points ◽  
Autoimmune Neuropathy ◽  
Car T

Key Points CAR T-cell therapy was safe and effective in a DLBCL patient with coexisting autoimmune neuropathy. CD19 CAR T-cell therapy may control refractory autoantibodies and monoclonal gammopathies.

scholarly journals Venous thromboembolism associated with CD19-directed CAR T-cell therapy in large B-cell lymphoma

2020 ◽  
Vol 4 (17) ◽  
pp. 4086-4090
Author(s):  
Hamza Hashmi ◽  
Abu-Sayeef Mirza ◽  
Alicia Darwin ◽  
Constantine Logothetis ◽  
Franco Garcia ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell Lymphoma ◽  
Bleeding Events ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Coagulation Abnormalities ◽  
Car T Cell Therapy ◽  
Key Points ◽  
Car T

Key Points VTE developed in 11% of lymphoma patients after CAR T-cell therapy and was managed safely with anticoagulation. Coagulation abnormalities after CAR T-cell therapy occur but do not commonly lead to bleeding events.

Quality of life (QOL) in patients undergoing CAR-T therapy versus stem cell transplant (SCT).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6594-6594 ◽  
Author(s):  
Surbhi Sidana ◽  
Amylou C. Dueck ◽  
Michelle Burtis ◽  
Joan M. Griffin ◽  
Gita Thanarajasingam ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Cell Transplant ◽  
Short Term ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Significant Difference ◽  
Car T

6594 Background: Given the significant short-term adverse effects of CAR-T cell therapy, it is important to evaluate its impact on QOL of patients in addition to efficacy, compared with established forms of cellular therapy like SCT. Methods: QOL was evaluated prospectively in patients undergoing CAR-T therapy, autoSCT & alloSCT for hematologic malignancies. QOL was assessed with FACT-G at baseline, 2 weeks and monthly for 6 months thereafter. Functional well-being (FWB), physical WB (PWB) emotional WB (EWB) & social WB (SWB) and change over time were compared across groups. Results: 45 patients were recruited (CAR-T: 10; Auto SCT: 22; Allo SCT: 13) with follow up for 2 weeks & 1 month available for 23 &15 patients, respectively (Table). There was no statistically significant difference in baseline total QOL scores (p=0.13), though scores were lower in the alloSCT group (85,84,68). EWB &FWB were numerically higher in the CAR-T group, followed by autoSCT group. At 2 weeks, overall QOL decreased by only 2 points in CAR-T group vs. 22 & 18 points in auto & alloSCT groups (p=0.09). Change in PWB vs. baseline was less pronounced in the CAR-T group (-1, -9, -13, p=0.03). At 1 month, overall QOL was 6 points lower than baseline in CAR-T group vs. 3 and 14 points lower in auto & alloSCT groups, respectively (p=0.34). Importantly, PWB had at least returned to baseline in the CAR-T group. Conclusions: Preliminary data show that patients undergoing CAR-T cell therapy do not experience a more significant decline in QOL compared with auto & allo SCT, and may experience fewer physical side effects in the short-term. Accrual & follow-up are ongoing. [Table: see text]

KarMMa-4: Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T-cell therapy in high-risk newly diagnosed multiple myeloma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS8053-TPS8053
Author(s):  
Saad Z. Usmani ◽  
Jesus G. Berdeja ◽  
Anna Truppel-Hartmann ◽  
Yizhou Fei ◽  
Honeylet Wortman-Vayn ◽  
...  
Keyword(s):  
T Cell ◽  
High Risk ◽  
Cell Therapy ◽  
Stage Iii ◽  
Newly Diagnosed ◽  
Target Dose ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

TPS8053 Background: High-risk (R-ISS stage III) newly diagnosed multiple myeloma (NDMM) has a poor prognosis (median PFS, 29 mo), highlighting the need for novel disease-targeting approaches (Palumbo A, et al. J Clin Oncol 2015;33:2863-2869). Ide-cel, a BCMA-directed CAR T cell therapy, demonstrated deep, durable responses in heavily pretreated patients (pts) with relapsed and refractory MM (RRMM; Raje N, et al. N Engl J Med 2019;380:1726-1737; Munshi NC, et al. J Clin Oncol 2020;38[suppl 15]. Abstract 8503), including those with high-risk (R-ISS stage III) RRMM. In this population, earlier use of ide cel—when there may be more bone marrow reserve, more healthy peripheral blood mononuclear cells, a less compromised immune status, and less extensive disease to debulk before cell therapy—may result in improved outcomes vs standard therapies and offer an opportunity to replace transplant with CAR T cell therapy. Methods: KarMMa-4 (NCT04196491), a multicenter, open-label, phase 1, single-arm study, is currently evaluating ide-cel in pts with high-risk NDMM, defined as R-ISS stage III (ISS stage III [serum ß2 microglobulin ≥ 5.5 mg/L] and cytogenetic abnormalities t(4;14), del(17p), and/or t(14;16) by interphase FISH; or ISS stage III and serum LDH > ULN). Pts must have received ≤ 3 cycles of the induction regimens listed below, be aged ≥ 18 years, and have ECOG PS 0-1. Nonsecretory MM and CNS involvement are exclusion criteria. Pts can enroll between induction cycles 1 and 3. Permitted cycle 1 regimens are carfilzomib + lenalidomide (LEN) + dexamethasone (DEX) ± daratumumab (DARA; KRd ± DARA), LEN + bortezomib (BOR) + DEX ± DARA (RVd ± DARA), or cyclophosphamide + BOR + DEX (CyBorD). Induction cycles 2-4 are limited to KRd or RVd, with DEX omitted during cycle 3. Pts will undergo T cell collection via leukapheresis after cycle 3, and ide-cel will be manufactured during cycle 4. Stem cell collection for future use may be conducted after cycle 3 (following leukapheresis) or 4 (before lymphodepletion). Ide-cel is infused after 2 days of rest following lymphodepletion with 3 days of fludarabine 30 mg/m2 + cyclophosphamide 300 mg/m2. LEN-based maintenance may be provided upon bone marrow recovery or 90 days after ide-cel infusion, whichever is later. Dose-limiting toxicity and safety are the primary endpoints. Secondary endpoints include complete response (CR) rate and overall response rate, duration of response, time to CR, time to start of maintenance, feasibility of initiating maintenance, PFS, overall survival, and pharmacokinetics. Exploratory endpoints include LEN maintenance safety, minimal residual disease, immunogenicity and biomarkers. The starting ide-cel target dose is 450 × 106 CAR+ T cells, with dose escalation/de-escalation (150, 300, and 800 × 106 CAR+ T cells). Upon determination of optimal target dose, 12 pts will be enrolled in the dose-expansion phase. Clinical trial information: NCT04196491.

scholarly journals Clonal expansion of CAR T cells harboring lentivector integration in the CBL gene following anti-CD22 CAR T-cell therapy

2019 ◽  
Vol 3 (15) ◽  
pp. 2317-2322 ◽  
Author(s):  
Nirali N. Shah ◽  
Haiying Qin ◽  
Bonnie Yates ◽  
Ling Su ◽  
Haneen Shalabi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Clonal Expansion ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell Therapy ◽  
Key Points ◽  
Car T ◽  
Clonal Nature

Key Points Reexpansion of CAR T cells led to further investigations which confirmed the clonal nature of this expansion.

scholarly journals CAR T-cell therapy is effective for CD19-dim B-lymphoblastic leukemia but is impacted by prior blinatumomab therapy

2019 ◽  
Vol 3 (22) ◽  
pp. 3539-3549 ◽  
Author(s):  
Vinodh Pillai ◽  
Kavitha Muralidharan ◽  
Wenzhao Meng ◽  
Asen Bagashev ◽  
Derek A. Oldridge ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Therapy ◽  
Lymphoblastic Leukemia ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell Therapy ◽  
Key Points ◽  
Car T ◽  
Rate Of Failure ◽  
Cd19 Expression

Key Points Preinfusion dim CD19 expression and rare CD19– events in B-ALL do not affect relapses or responses to CD19-directed CAR T-cells. Prior blinatumomab treatment increases the rate of failure to achieve MRD– remission and CD19– MRD and relapse.

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