scholarly journals Adverse Events Following CAR T-Cell Therapy: A Single Institution Retrospective Analysis of Toxicities Following CAR T-Cell Therapy for Children and Young Adults with Relapsed Refractory B-Cell Acute Lymphoblastic Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1731-1731
Author(s):  
Sara K. Silbert ◽  
Elizabeth M. Holland ◽  
Seth M. Steinberg ◽  
Lauren Little ◽  
Toni Foley ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Cell Therapy ◽  
Phase I ◽  
Median Number ◽  
Toxicity Profile ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Abstract Introduction: CAR T-cells have demonstrated remarkable ability to induce complete remission in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r ALL). This success, however, is tempered by the toxicities associated with CAR T-cell therapy. Much has been published on cytokine release syndrome (CRS), but, to date, a comprehensive profile of specific end organ toxicities secondary to CAR T-cell therapy in the pediatric and young adult population is lacking. Methods: This retrospective, single center study, was performed to characterize the specific adverse events (AEs) experienced by pediatric and young adult patients during the first 30 days following CAR T-cell infusion. AEs graded using Common Terminology Criteria for Adverse Events (CTCAE) were collected from all patients with r/r ALL treated on one of three phase I CAR T-cell trials (CD19, CD22, and CD1922) at the Pediatric Oncology Branch of the National Cancer Institute at the National Institutes of Health from 2012-2020. The primary objective was to determine the incidence of all severe AEs, defined as > grade (Gr) 3 AEs, overall and by organ system, attributed to research or disease. Secondary objectives were to stratify severe AEs based on development of CRS and CRS grade (using ASTCT CRS grading criteria). Descriptive statistics were reported along with comparisons of continuous parameters using Mann-Whitney and binomial parameters using Fischer's exact tests. Results: We reviewed AE data from 134 patients with r/r ALL receiving one of 3 unique CAR T-cell constructs (Table). The median age was 15.2 years (Interquartile range (IQR) 9.5-21.2). The median number of prior therapies was 5 (IQR 3-6) and 57% had received a prior hematopoietic stem cell transplant (HSCT). Amongst the 134 patients, a total of 1747 individual > Gr 3 AEs were experienced by 133 patients (99%) during the first 30 days following CAR infusion (Figure 1A). The median number of > Gr 3 AEs per patient was 10 (IQR 4.8-19). Cytopenias (including neutropenia, thrombocytopenia and anemia) comprised the vast majority of total > Gr 3 AEs (n=983, 56.3%). The most common severe (> Gr 3) AEs were thrombocytopenia (n=433, 24.8%), metabolic abnormalities (i.e. electrolyte derangements) (n=333, 19.1%), neutropenia (n=332, 19%), and anemia (n=218, 12.5%). With exclusion of cytopenias, 764 > Gr 3 AEs were experienced by 111 patients (83%), with a median of 4 (IQR 1-8.3) > Gr 3 AEs per patient. One grade 5 pulmonary AE occurred in the setting of acute respiratory distress syndrome (ARDS). Focusing on non-cytopenia AEs (Figure 1B), metabolic AEs made up 43.6% of AEs; hepatic toxicities (n=115, 15%), febrile neutropenia (n=114, 14.9%), and cardiovascular toxicities (n=59, 7.7%) were the next most frequent. Of the 134 patients, 104 (77.6%) developed CRS. All 30 patients without CRS had at least 1 > Gr 3 AE (median 6, IQR 3-11.3). In contrast, the median number of > Gr 3 AEs in those with CRS was 11.5 (IQR, 6-21.5), (p=0.0021). When stratified by CRS Gr 1-2 versus CRS Gr 3-4 (Figure 2), patients with higher-grade CRS also had a higher median number of > Gr 3 AEs per patient (p= 0.0017). Conclusions: Among 134 children and young adults with r/r ALL receiving phase I CAR T-cells, we found a high incidence (99%) of severe AEs, with a per patient median of 10 (IQR 4.8-19) > Gr 3 AEs. While the majority of > Gr 3 AEs were cytopenias, 17 different categories of AEs were experienced. The development and severity of CRS associated with an increase in the median number of severe AEs per patient. As phase I trials of CAR T-cell therapy expand, it is imperative to understand the full toxicity profile of these therapies. While the definition and refined grading of CRS has helped advance the field, there is a gap in knowledge regarding patient specific end-organ toxicities beyond CRS. Our data help establish a foundation for the full toxicity profile experienced by patients enrolling on phase I CAR T-cell trials. With an emerging role for earlier intervention for CRS, we anticipate that the toxicity burden will decrease. Next steps include characterizing the specific toxicities within each AE category, evaluating duration and time to resolution, distinguishing attribution to research versus disease and studying the impact of earlier use of tocilizumab on toxicity profile. Future directions will incorporate assessment of baseline organ function pre-CAR and its impact on development of post CAR severe AEs. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Anakinra (AKR) prophylaxis (ppx) in patients (pts) with relapsed/refractory multiple myeloma (RRMM) receiving orvacabtagene autoleucel (orva-cel).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2537-2537
Author(s):  
Luciano J. Costa ◽  
Sham Mailankody ◽  
Paul Shaughnessy ◽  
Parameswaran Hari ◽  
Jonathan L. Kaufman ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Phase 1 ◽  
Median Number ◽  
Control Group ◽  
T Cell Therapy ◽  
Disease Response ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

2537 Background: Orva-cel is a B-cell maturation antigen–targeted chimeric antigen receptor (CAR) T cell therapy being evaluated in the phase 1/2 EVOLVE study (NCT03430011) in pts with RRMM who had at least 3 prior lines of therapy (Tx). We previously reported safety and efficacy in the phase 1 study and established the recommended dose (RD) of orva-cel as 600 × 106 CAR+ T cells (Mailankody et al, ASCO 2020). Cytokine release syndrome (CRS), a dominant toxicity of CAR T cell therapy, is mediated in part by IL-1. We explore the role of ppx with AKR, an IL-1 signaling inhibitor, on reducing the incidence of grade (G) ≥2 CRS after orva-cel treatment at the RD. Methods: Fourteen pts were enrolled sequentially for AKR ppx and treated with orva-cel at the RD. The non-AKR ppx control group comprised the remainder of the phase 1 pts receiving orva-cel at the RD (n = 19). The median follow-up (range) was 3.0 mo (1.8–6.2) for the AKR ppx group and 8.8 mo (5.3–12.2) for the non-AKR ppx group. AKR was administered as 100 mg SC the night before orva-cel infusion, 3 h before the infusion (Day 1), and q24 h on Days 2–5. Dosing was increased to q12 h if CRS developed. CRS was graded by Lee (2014) criteria. Tocilizumab (T) and steroids (S) were used per protocol-specified treatment management guidelines. Results: Disease characteristics and outcomes are shown in the table. In AKR ppx and non-AKR ppx groups, median number of prior regimens was 6 and 5, and bridging Tx was used in 57% and 68% of pts, respectively. The total frequency of CRS was similar in the 2 groups, but with less G 2 in the AKR ppx pts; relative risk (95% CI) = 0.54 (0.21, 1.38). No G ≥3 CRS was seen in either group. The incidence of neurological events (NE), G ≥3 infection, and macrophage activation syndrome/hemophagocytic lymphohistiocytosis (MAS/HLH) was similar. T and S use was numerically lower with AKR ppx. Orva-cel expansion kinetics were similar in the 2 groups. All pts had a 2-month efficacy assessment, with ORR in 100% of AKR ppx and 95% of non–AKR ppx pts. Conclusions: In this nonrandomized evaluation of AKR ppx with orva-cel treatment, the incidence of G ≥2 CRS was lower in pts receiving AKR ppx. The use of AKR ppx produced no adverse effect on the incidence of NE, infection, or MAS/HLH, nor on orva-cel expansion or disease response. These results warrant further study of AKR ppx in CAR T cell therapy. Clinical trial information: NCT03430011. [Table: see text]

A phase I trial of regional mesothelin-targeted CAR T-cell therapy in patients with malignant pleural disease, in combination with the anti-PD-1 agent pembrolizumab

2021 ◽  
pp. candisc.0407.2021
Author(s):  
Prasad S Adusumilli ◽  
Marjorie G Zauderer ◽  
Isabelle Riviere ◽  
Stephen B Solomon ◽  
Valerie W Rusch ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Phase I ◽  
Phase I Trial ◽  
Pleural Disease ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

scholarly journals Clinical Efficacy of Polatuzumab Vedotin in Patients with Relapsed/Refractory Large B-Cell Lymphoma after Standard of Care Axicabtagene Ciloleucel

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 16-17
Author(s):  
Paolo Strati ◽  
Grace Watson ◽  
Sandra B. Horowitz ◽  
Ranjit Nair ◽  
Maria Alma Rodriguez ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
Median Number ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Introduction. The outcome of patients with large B-cell lymphoma (LBCL) relapsing or progressing after anti-CD19 CAR T-cell therapy is dismal, and novel therapeutic strategies are needed. Polatuzumab vedotin (PV) is a CD79b-directed antibody-drug conjugate, approved by the FDA in combination with bendamustine and rituximab for the treatment of patients with LBCL who relapse or progress after at least 2 lines of systemic therapy. CD79b targeting is an appealing strategy after failure of anti-CD19 CAR T-cell therapy, but the activity of PV in this setting has not been investigated. Methods. This is a retrospective analysis of patients with relapsed/refractory LBCL after standard of care axicabtagene ciloleucel (axi-cel), and treated with standard of care PV at MD Anderson Cancer Center between 07/2019 and 03/2020. PV was given at the standard dose of 1.8 mg/kg IV every 3 weeks in all patients. PV was administered with rituximab, with or without bendamustine. Response to treatment and progression were defined according to 2014 Lugano criteria. Results. Eight patients were included in the analysis: median age was 54 (range, 41-70 years), 7 (87.5%) were male, and all had an IPI score > 3. Median number of systemic therapies before axi-cel was 3 (range, 2-7), and median number of systemic therapies between axi-cel and PV use was 1 (range, 0-3); 1 patient previously had autologous stem cell transplant (SCT), and 2 had allogeneic SCT. Three (37.5%) patients were primary refractory to axi-cel therapy, and median time from axi-cel to PV was 6 months (range, 1-12 months). All patients were biopsied at time of relapse after axi-cel, and in all cases lymphoma was CD19+ CD79b+ by immunohistochemistry/flow cytometry. At time of PV initiation, median absolute neutrophil count was 2.6 (range, 0.4-4.7 X109/L), median platelet count was 141 X109/L (range, 7-245 X109/L), median serum creatinine was 0.9 mg/dL (range, 0.5-1.5 mg/dL), and all patients had LDH above upper limit of normal. Median number of PV cycles was 2 (range, 1-3): PV was combined with rituximab in all patients but administered with bendamustine in only 3 (37.5%). No significant toxicity, prompting dose reduction or treatment discontinuation, was observed. A response was achieved in 4 (50%) patients, represented by partial remission (PR) in all cases, whereas 4 (50%) patients were refractory. All patients stopped PV, 6 (75%) because of progression, 1 (12.5%) to proceed to allogeneic SCT while in PR, and 1 (12.5%) to proceed to an immunotherapy clinical trial (despite absence of progression). After a median follow up of 29 weeks (95% CI, 16-31 weeks), all patients progressed/died, and median PFS was 5 weeks (95% CI, 2-8 weeks) (Figure). At most recent follow-up, 5 (62.5%) died, and median OS was 15 weeks (95% CI, 9-21 weeks)(Figure); causes of death included progression in 4 patients, and transplant-related complications in 1. Discussion. PV in combination with rituximab is safe but has limited and short-lasting activity in relapsed/refractory LBCL after anti-CD19 CAR T-cell therapy. These findings need to be confirmed in larger and prospective studies. The activity of PV, alone or in combination with novel drugs, for the treatment of patients with CD19-negative relapses after CAR T-cell therapy remains to be investigated. Figure Disclosures Westin: 47 Inc:Consultancy;Curis:Consultancy;Janssen:Consultancy;Novartis:Consultancy;Genentech:Consultancy;Juno:Consultancy;Kite:Consultancy;MorphoSys:Consultancy;Unum:Consultancy.Neelapu:Acerta:Research Funding;Takeda Pharmaceuticals:Patents & Royalties;Pfizer:Other: personal fees;Unum Therapeutics:Other, Research Funding;N/A:Other;Novartis:Other: personal fees;Adicet Bio:Other;Legend Biotech:Other;Bristol-Myers Squibb:Other: personal fees, Research Funding;Merck:Other: personal fees, Research Funding;Kite, a Gilead Company:Other: personal fees, Research Funding;Incyte:Other: personal fees;Calibr:Other;Precision Biosciences:Other: personal fees, Research Funding;Allogene Therapeutics:Other: personal fees, Research Funding;Cell Medica/Kuur:Other: personal fees;Poseida:Research Funding;Celgene:Other: personal fees, Research Funding;Cellectis:Research Funding;Karus Therapeutics:Research Funding.

scholarly journals Overview of Adverse Events Associated With Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy

2021 ◽  
Author(s):  
Ekaterina Vorozheikina ◽  
Magdalena Ruiz ◽  
Maria Leticia Solari ◽  
Dmitry Ostasevich ◽  
Luis Mendoza
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Clinical Manifestations ◽  
Antigen Receptor ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Anti-CD19 chimeric antigen receptor (CAR) T-cells represent a novel immunotherapy that has shown remarkable success in the treatment of adult relapsed or refractory (R/R) B-cell non-Hodgkin's lymphoma, adult R/R mantle cell lymphoma, and R/R acute paediatric lymphoblastic leukaemia. One barrier to the widespread use of CAR T-cell therapy is toxicity, primarily cytokine release syndrome (CRS) with a variable grade of severity. The main manifestations of CRS are fever, hypotension, cytopenia, organ dysfunction among others. Neurological toxicities vary widely and range from headaches to encephalopathy. In addition, anti-CD19 CAR T-cell therapy provokes an array of less frequent events, such as coagulopathies, delayed cytopenia, and cardiovascular toxicities. In general, toxicities are usually reversible and resolve on their own in most cases, though severe cases may require intensive care and immunosuppressive therapy. Deaths due to CRS, neurologic toxicity and infectious complications have been reported, which highlights the gravity of these syndromes and the critical nature of appropriate intervention. In this paper, we look at all available FDA- and EMA-approved information about the pathophysiology, clinical manifestations, risk factor reviews of existing toxicity grading systems, current management strategies, and guidelines for anti-CD19 CAR T-cell toxicities. We also present new approaches, which are under investigation, to mitigate these adverse events.

Real-world adverse events associated with CAR T-cell therapy among adults age ≥ 65 years

2020 ◽  
Author(s):  
Marjorie E. Zettler ◽  
Bruce A. Feinberg ◽  
Eli G. Phillips Jr ◽  
Andrew J. Klink ◽  
Sonam Mehta ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Cell Therapy ◽  
Real World ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

scholarly journals A Multi-Center Retrospective Study of Polatuzumab for Patients with Large B-Cell Lymphoma Relapsed after Standard of Care CAR T-Cell Therapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2495-2495
Author(s):  
Sushanth Gouni ◽  
Allison C. Rosenthal ◽  
Jennifer L. Crombie ◽  
Andrew Ip ◽  
Manali Kamdar ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
Median Number ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Abstract Introduction. About 60% of patients with large B-cell lymphoma (LBCL) relapse after standard of care (SOC) anti-CD19 autologous chimeric antigen receptor (CAR) T-cell therapy, CD19 downregulation representing a major mechanism of resistance. Therefore, agents able to target B-cell antigens other than CD19 could be clinically effective for these patients. Polatuzumab vedotin (PV) is an antibody-drug conjugate targeting CD79b, and approved by the FDA in combination with bendamustine and rituximab for patients with relapsed or refractory (r/r) LBCL. Patients who relapsed after CAR T-cell therapy were not included in the registration study, and reports of PV use after CAR T-cells in real world practice are very limited. Methods. This is a multi-center retrospective analysis of patients with LBCL who relapsed after SOC CAR T-cell therapy and subsequently received SOC PV with or without rituximab and bendamustine between 07/2019 and 04/2021. PV was given at the standard dose of 1.8 mg/kg IV every 3 weeks in all patients (except for one patient, who received 1.4 mg/Kg). Response to treatment and progression were defined according to 2014 Lugano criteria. Survival curves were calculated using Kaplan-Meier estimates, and were compared between subgroups using the log-rank test. Cox regression was used for multivariate analysis (MVA). Results. Fifty-four patients were included in the study: median age was 59 (range, 22-79 years), 38 (70%) were male, and 30 (56%) had an internal prognostic index score > 3. Median number of systemic therapies before CAR T-cell therapy was 2 (range, 2-6), 16 (30%) patients previously had autologous stem cell transplant (SCT), and 2 (4%) had allogeneic SCT. Sixteen (30%) patients were primary refractory to CAR T-cell therapy, and median time from CAR T-cell therapy to PV was 5 months (range, 1-40 months). CD19 status at time of relapse after CAR T-cell therapy was assessed by immunohistochemistry and/or flow cytometry in 41 patients, and positive in 34 (83%); CD79b status was assessed in 14 patients, and positive in all cases (100%). Thirty-two (59%) patients received PV-based therapy immediately after CAR T cell therapy, while 22 (41%) had intervening treatments (median 1, range 1-5). At time of PV initiation, median absolute neutrophil count was 2.9 (range 0.5-19 X10 9/L), median platelet count was 87 X10 9/L (range 15-437 X10 9/L), median serum creatinine was 0.9 mg/dL (range 0.4-22 mg/dL), and 44 (81%) patients had elevated serum lactate dehydrogenase (LDH). The median number of PV cycles was 2 (range, 1-16): PV was combined with rituximab in 51 (94%) patients, and administered with bendamustine in 33 (61%). A response was achieved in 24 (45%) patients, including complete remission (CR) in 8 (14%) patients and partial remission in 16 (30%)(Figure A), with a median duration of response of 11 weeks (95%CI, 5-17 weeks). No significant association between baseline characteristics and response was observed. To date, 49 (91%) patients stopped PV: 38 (70%) due to progression, 7 (13%) because of CR/patient decision, 3 (6%) to proceed to allogeneic SCT, and 1 (2%) to proceed to an immunotherapy clinical trial (despite absence of progression). No patients stopped therapy because of toxicity. After a median follow up of 45 weeks (95% CI, 20-70 weeks), 44 (81%) patients progressed/died, and median PFS was 9 weeks (95% CI, 4-14 weeks). To date, 34 (63%) died, and median OS was 16 weeks (95% CI, 13-19 weeks)(Figure B). Causes of death included progression in 31 patients and transplant-related complications in 3. On univariate analysis, a shorter median progression-free survival (PFS) was observed for patients with bone marrow (BM) involvement (3 vs 10 weeks, p=0.002), prior central nervous system involvement (4 vs 10 weeks, p=0.02), and elevated LDH (6 months vs not reached, p=0.004). On MVA, the association was maintained only for BM involvement (hazard ratio [HR] 4.8; 95% confidence interval [CI] 1.6-12.5, p=0.004) and elevated LDH (HR 5; 1.4-16.7, p=0.01)(Figure C). Discussion. PV is safe and effective, but has short duration of response in r/r LBCL after anti-CD19 CAR T-cell therapy, except for patients with normal LDH. Studies aimed at better characterizing intrinsic mechanism of resistance, including upregulation of BCL2 family proteins, to favor the development of more effective PV-based combination strategies for these patients, are warranted. Figure 1 Figure 1. Disclosures Crombie: Roche: Research Funding; Merck: Research Funding; Abbvie: Research Funding; Bayer: Research Funding; Karyopharm: Consultancy; Incyte: Consultancy. Kamdar: Celgene (BMS): Consultancy; Adaptive Biotechnologies: Consultancy; Genentech: Research Funding; Kite: Consultancy; AstraZeneca: Consultancy; ADC Therapeutics: Consultancy; Genetech: Other; TG Therapeutics: Research Funding; SeaGen: Speakers Bureau; Celgene: Other; KaryoPharm: Consultancy; AbbVie: Consultancy. Hess: ADC Therapeutics: Consultancy; BMS: Speakers Bureau. Neelapu: Takeda Pharmaceuticals and related to cell therapy: Patents & Royalties; Kite, a Gilead Company, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics (Cogent Biosciences), Allogene, Precision BioSciences, Acerta and Adicet Bio: Research Funding; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics and Bluebird Bio: Honoraria; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Kuur, Incyte, Precision BioSciences, Legend, Adicet Bio, Calibr, and Unum Therapeutics: Other: personal fees. Lin: Novartis: Consultancy; Bluebird Bio: Consultancy, Research Funding; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Gamida Cell: Consultancy; Sorrento: Consultancy; Legend: Consultancy; Takeda: Research Funding; Merck: Research Funding; Vineti: Consultancy. Strati: Astrazeneca-Acerta: Research Funding; Roche-Genentech: Consultancy.

scholarly journals CD19 and CD30 CAR T-Cell Immunotherapy for High-Risk Classical Hodgkin’s Lymphoma

2021 ◽  
Vol 10 ◽  
Author(s):  
YuanBo Xue ◽  
Xun Lai ◽  
RuiLei Li ◽  
ChunLei Ge ◽  
BaoZhen Zeng ◽  
...  
Keyword(s):  
T Cell ◽  
High Risk ◽  
Adverse Events ◽  
Cell Therapy ◽  
Low Doses ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Severe Adverse Events

BackgroundIn clinical applications of CAR T-cell therapy, life-threatening adverse events including cytokine release syndrome and neurotoxicity can lead to treatment failure. Outcomes of patients treated with anti-CD30 CAR T- cell have been disappointing in relapsing/refractory (r/r) classical Hodgkin’s Lymphoma (cHL).MethodsIn order to understand the applicable population of multiple CAR T-cell therapy, we examined the expression of CD19, CD20, and CD30 by immunohistochemistry (IHC) in 38 paraffin-embedded specimens of cHL. In the past two years, we found only one patient with cHL who is eligible for combined anti-CD19 and CD30 CAR T-cell treatment. This patient’s baseline characteristics were prone to severe adverse events. We treated this patient with low doses and multiple infusions of anti-CD19 and CD30 CAR T-cell.ResultsThe positive expression of CD19+ + CD30+ in Reed-Sternberg (RS) cells is approximately 5.2% (2/38). The patient we treated with combined anti-CD19 and CD30 CAR T-cell did not experience severe adverse events related to CAR T-cell therapy and received long term progression-free survival (PFS).ConclusionFor high risk r/r cHL patients, low doses of CAR T-cell used over different days at different times might be safe and effective. More clinical trials are warranted for CD19 and CD30 CAR T-cell combination therapy.

scholarly journals Novel Therapies for the Treatment of Patients with Relapsed/Refractory Multiple Myeloma: A Review of Clinical Trials

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 43-44
Author(s):  
Ahmad Iftikhar ◽  
Muhammad Ahmad ◽  
Pranali Pachika ◽  
Faryal Razzaq ◽  
Muhammad Ashar Ashar Ali ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
T Cell ◽  
Cell Therapy ◽  
Phase I ◽  
Phase I Trial ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Introduction: Multiple myeloma (MM) is a neoplastic proliferation of plasma cells. It is the second most common hematological malignancy in the US. Although it is associated with poor prognosis, newer therapies have improved outcomes in MM patients. This review aims to describe novel therapies used for the treatment of relapsed/refractory multiple myeloma (RRMM). Methods: A literature search was performed on Embase and clinicaltrials.gov using the keyword "Multiple Myeloma" from 1/1/2016 to 6/25/2020 for identifying ongoing clinical trials in the treatment of RRMM. After detailed scrutiny, we included 23 ongoing clinical trials (N=4362). We excluded case reports, case series, review articles, meta-analysis, and observational studies. Results: We summarized the interim results from ongoing clinical trials evaluating treatment of RRMM under following newer categories of drugs: Immunomodulatory drugs In a phase 1b/IIa trial (NCT02773030, N=51) evaluating the efficacy of a novel immunomodulators, iberdomide CC-220 + dexamethasone (Dex) yielded an overall response rate (ORR) of 31%, clinical benefit (CB) was seen in 51% of the patients, and disease control (DC) in 88% of the patients and it was well tolerated by RRMM patients. There are other ongoing clinical trials evaluating the efficacy of Avadomide (CC-122), CC-92480 in RRMM. Alkylating agents In a phase I/II trial (NCT01897714, N=45), melphalan-flufenamide (melflufan) + Dex yielded an ORR of 31%, it was well tolerated with 49% CB. Phase III OCEAN trial (NCT03151811, N=450) is currently ongoing to compare melflufen + Dex vs. pomalidomide (Pom) + Dex. Apoptotic agents A phase 3 trial BELLINI (NCT02755597, N=291) evaluated the efficacy of veneteclox (Ven, Bcl-2 inhibitor) by randomizing patients to either Ven or Placebo arm. With a median follow up of 28.6 months (m), progression free survival (PFS) was 23.2m in the Ven arm vs. 11.4m in placebo. The interim results from a phase I/II trial (NCT03314181, N=104) of Ven + daratumumab (Dara) + Dex showed ORR of 96% with ≥ very good partial response (VGPR) of 96%. The addition of Bortezomib (Bor) to VenDaraDex had a slightly low ORR of 92%, with ≥VGPR of 79%. Another phase I/II trial (NCT01794520, N=117) is in progress to assess the efficacy and safety of Ven as monotherapy. Monoclonal Antibodies (MoAb) A phase I/II trial (NCT01421186, N=91) evaluated the efficacy of MOR202, which is a novel MoAb. MOR202 was evaluated in three arms; MOR202 + Dex, MOR202 + Lenalidomide (Len) + Dex and MOR202 + Pom + Dex. The interim analysis showed the ORR of 65% with MOR202 + Len + Dex which was better than ORR of 48% with MOR202 + Pom + Dex, while the use of MOR202 + Dex yielded only 28% ORR. Antibody-drug conjugate (ADC) Four ongoing trials are evaluating the efficacy of ADC (belantamab mafodotin), and the interim results are available for two trials. In phase II DREAMM-2 trial (NCT03525678, N=221) evaluating 2 doses of GSK2857916, 2.5mg/kg dose yielded ORR of 31% while 3.4mg/kg showed ORR of 34%. Another phase I trial (NCT02064387, N=79) evaluated belantamab mafodotin in RRMM and other hematologic malignancies expressing B-cell maturation antigen (BCMA). The results were promising with ORR of 60%. Bispecific T-cell engagers (BiTE) Phase I trial of BiTE AMG 420 (NCT02514239, N=43) showed favorable results with ORR 70%, and CR 12%. The interim results from another phase I trial (NCT03486067, N=115) which evaluated the efficacy of BiTE CC-93269 showed 43% ORR and CR 17%. CAR-T Cell therapy CAR-T cell therapy is also being studied in RRMM with JNJ-68284528 directed against BCMA in a phase Ib trial (NCT03548207, N=118). The interim analysis of 29 response evaluable patients out of 118 reported 100% ORR with stringent CR 76%. PK13 Inhibitors In a phase I/II study (NCT00401011, N=84) evaluating perifosine + Bor +/- Dex, ORR of 41% was observed in Bor RR patients, and therapy was well tolerated with PFS of 6.4m and mOS of 25m. Conclusion: This review demonstrates novel and promising therapies which are currently in early phase clinical trials for the treatment of RRMM. Based on interim results, Iberdomide, melflufan, Ven, MoAb MOR202, ADC belantamab mafodotin, BiTE Molecule AMG 420, BCMA CAR-T cell therapy and perifosine have shown promising early activity and safety data in RRMM patients. Additional exploratory clinical trials are needed to confirm the efficacy and safety of these agents. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

scholarly journals Immune-related Adverse Events Associated With Checkpoint Inhibition in the Setting of CAR T Cell Therapy: A Case Series

2020 ◽  
Vol 20 (3) ◽  
pp. e118-e123 ◽  
Author(s):  
Swetha Kambhampati ◽  
Lissa Gray ◽  
Bita Fakhri ◽  
Mimi Lo ◽  
Khoan Vu ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Cell Therapy ◽  
Case Series ◽  
Checkpoint Inhibition ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T
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