scholarly journals 15. Evaluation of Retained Immunity for Tetanus-Diphtheria and Pneumococcal Vaccines in Recipients of Cellular Therapies

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S131-S132
Author(s):  
Georgios Angelidakis ◽  
Roy F Chemaly ◽  
Partow Kebriaei ◽  
Nadim J Ajami ◽  
Micah M Bhatti ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Pneumococcal Vaccination ◽  
Cell Transplant ◽  
Research Support ◽  
T Cell Therapy ◽  
Hematopoietic Stem ◽  
Cellular Therapies ◽  
Increased Risk ◽  
Car T

Abstract Background Infectious complications in cancer patients (pts) who have received T-cell therapies are similar to those in autologous hematopoietic stem cell transplant (HCT) recipients, who - because they lose prior acquired immunity after undergoing conditioning regimens and transplantation- may be at an increased risk for vaccine-preventable infections. We sought to determine seroprotection rates against pneumococcus and tetanus-diphtheria before and after cellular therapies. Methods In this ongoing prospective observational cohort study, we enrolled pts with any type of cancer who received cellular therapy with chimeric antigen receptor modified T cell (CAR-T), natural killer CAR-T, or T-cell receptor- directed immunotherapies at MD Anderson Cancer Center from January 2020 through May 2021. We performed antibody assays for diphtheria, tetanus, and pneumococcus before, at 1 month, and between 3-6 months after T-cell therapy for each pt regardless of vaccination history. Results Of 38 pts enrolled, 27 (71%) were men and 25 (66%) had non-Hodgkin lymphoma (Table 1); 38 (100%) and 17 (45%) had a history of previous diphtheria-tetanus-acellular pertussis (Tdap) and pneumococcal vaccination, respectively (Table 2). Tetanus serologies were positive for all pts tested before, at 1 month and 3-6 months after T cell therapy (37/37 [100%], 22/22 [100%], and 13/13 [100%], respectively). Diphtheria serologies were positive for most pts tested before, at 1 month and 3-6 months after therapy (35/37 [95%], 20/22 [91%], and 11/13 [85%], respectively]. Pneumococcal serologies were positive for 8 out of 37 [22%] pts before therapy, among these 8 pts, 4 had positive serologies 1 month after therapy, and 2 of 3 tested 3-6 months after therapy had positive serologies. One pt received a pneumococcal vaccine 10 months after therapy but had negative serologies post-vaccination. Conclusion Most pts who received T-cell therapy retained their immunity for diphtheria and tetanus, but most also lost their immunity for pneumococcus. This suggests that the standard of care for pts receiving T-cell therapy should include more robust strategy for pneumococcal vaccination, but its timing, need for booster dosing, and antibody response needs to be determined in future trials. Disclosures Roy F. Chemaly, MD, MPH, FACP, FIDSA, AiCuris (Grant/Research Support)Ansun Biopharma (Consultant, Grant/Research Support)Chimerix (Consultant, Grant/Research Support)Clinigen (Consultant)Genentech (Consultant, Grant/Research Support)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Merck (Consultant, Grant/Research Support)Molecular Partners (Consultant, Advisor or Review Panel member)Novartis (Grant/Research Support)Oxford Immunotec (Consultant, Grant/Research Support)Partner Therapeutics (Consultant)Pulmotec (Consultant, Grant/Research Support)Shire/Takeda (Consultant, Grant/Research Support)Viracor (Grant/Research Support)Xenex (Grant/Research Support) Fareed Khawaja, MBBS, Eurofins Viracor (Research Grant or Support) Ella Ariza Heredia, MD, Merck (Grant/Research Support)

The pharmacist’s role in chimeric antigen receptor T cell therapy

2020 ◽  
Vol 26 (7) ◽  
pp. 1725-1731
Author(s):  
Jennifer P Booth ◽  
Carolyn L Kusoski ◽  
Julie M Kennerly-Shah
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Cell Transplant ◽  
T Cell Therapy ◽  
Hematopoietic Stem ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

The emergence and efficacy of chimeric antigen receptor (CAR) T cell therapy in previously incurable malignancies represents a promising paradigm shift in cancer care. However, it is not without significant clinical, operational, and financial considerations. Pharmacists should be prepared to fulfill the various roles in CAR T cell therapy provision including: policy development; electronic medical record build; patient and staff education; patient selection; procurement, storage, and handling; medication administration and supportive care; management of adverse reactions; and quality tracking. Our commentary provides an overview of the opportunities for pharmacy involvement in the implementation and maintenance of a CAR T cell therapy program with an emphasis on the importance of pharmacy involvement as part of a multidisciplinary approach to care. Although some institutions have dedicated a CAR T cell pharmacist to meet the demands of emerging CAR T cell therapy, we believe that clinical pharmacists practicing in hematopoietic stem cell transplant and hematology/oncology have the skills and training to fulfill the pharmacist’s role in CAR T cell therapy.

scholarly journals Impact of SARS-CoV-2 in hematopoietic stem cell transplant and CAR-T cell therapy recipients

2021 ◽  
Author(s):  
Muhammad Umair Mushtaq ◽  
Moazzam Shahzad ◽  
Sibgha Gull Chaudhary ◽  
Mary Luder ◽  
Nausheen Ahmed ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Cell Therapy ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
T Cell Therapy ◽  
Hematopoietic Stem ◽  
Car T Cell Therapy ◽  
Car T

Vaccine titers in lymphoma patients receiving chimeric antigen receptor T-cell therapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7555-7555
Author(s):  
Radhika Bansal ◽  
Paschalis Vergidis ◽  
Pritish Tosh ◽  
John W. Wilson ◽  
Matthew Hathcock ◽  
...  
Keyword(s):  
T Cell ◽  
Hepatitis B ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Aggressive Lymphoma ◽  
Cell Transplant ◽  
T Cell Therapy ◽  
Car T ◽  
The Impact

7555 Background: While CAR-T therapy is not myelo-ablative, patients with aggressive lymphoma treated with CD19 chimeric antigen receptor T cell therapy (CAR-T) are lymphodepleted and have prolonged B cell aplasia. The impact of CAR-T on immunologic protection from vaccine-preventable diseases (and thus the need to revaccinate) is not known. We report the vaccine titers of patients treated with axicabtagene ciloleucel (axi-cel) at Mayo Clinic. Methods: Retrospective chart review of adult lymphoma patients who received axi-cel from 9/2018 to 9/2020 for anti-viral and anti-bacterial titers prior to CAR-T infusion and at month 3 (MO3) post CAR-T. Results: Prior to CAR-T therapy, positive titer rate was highest for tetanus and lowest for Strep pneumoniae (Strep PNA) (Table). Similar trends were seen whether patients had stem cell transplant (ASCT) within 2 years of CAR-T (i.e. within immunization timeframe post ASCT) or not (Table). Compared to patients who had ASCT, those who did not had higher rate of positive titer for Strep PNA and lower rate for hepatitis B, Mumps, and VZV. The same trend for sero-positive rate were observed at MO3 post CAR-T. Patients with IgG<400 mg/dl received IVIG supplement for prophylaxis. Among the 23 patients who received IVIG, variable rate of conversion from negative to positive titers were seen for measles (1/2, 50%), mumps (2/3, 67%), rubella (2/3, 67%), varicella-zoster (VZV, 3/3, 100%), hepatitis A (6/6, 100%), hepatitis B (6/7, 86%) and Strep PNA (0/10, 0%). For patients who did not receive IVIG prophylaxis, there was one loss of seropositivity for Strep PNA (1/4, 25%). Conclusions: The presence of protective vaccine titers is variable for patients receiving CAR-T, regardless of recent ASCT. The loss of protective titers post CART was low. IVIG variably impacted vaccine titer status. Immunization remains important for patients with ASCT prior to CART, without completion of post ASCT immunization protocol. Further study is needed to inform the need for immunization and optimal timing post CART.[Table: see text]

scholarly journals 1098. Norovirus Infection in Cancer Patients Undergoing Chimeric Antigen Receptor T-cell Immunotherapy (CAR-T)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S578-S579
Author(s):  
Divya S Kondapi ◽  
Sasirekha Ramani ◽  
Adilene Olvera ◽  
Robert L Atmar ◽  
Mary K Estes ◽  
...  
Keyword(s):  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Lymphocytic Leukemia ◽  
Nucleic Acid Amplification ◽  
High Dose ◽  
Cell Transplant ◽  
Research Support ◽  
Hematopoietic Stem ◽  
Car T Cell ◽  
Car T

Abstract Background CAR-T is used to treat certain refractory hematological malignancies. B-cell aplasia and immunosuppression used to treat CAR-T side effects increase infection risk. Little data are available describing Norovirus (NoV) infections in CAR-T recipients. Methods We reviewed the medical records of 134 patients with NoV diarrhea (identified by nucleic acid amplification test) between 2016-2019. Of these patients, nine received CAR-T prior to developing NoV. Here we describe their demographics, clinical characteristics, treatments, and complications. Results The median age was 49 years (Table 1). Patients’ underlying malignancies included Non-Hodgkin’s Lymphoma (4), Acute Lymphoblastic Leukemia (3), Chronic Lymphocytic Leukemia (1) and metastatic Sarcoma (1). Prior to development of NoV, six patients had undergone hematopoietic stem cell transplant, and 1 had received checkpoint inhibitor therapy. Five patients experienced cytokine release syndrome after CAR-T, and 1 experienced CAR-T-related encephalopathy syndrome (Table 2). Two patients received interleukin-6 antagonist therapy, and one received high dose steroids. Time to diarrhea onset post-CAR-T cell infusion was variable(median 256days, IQR 26-523 days).Six had an absolute lymphocyte count&lt; 1000/mm3 at diarrhea onset. Three had diarrhea for &gt;14 days; median diarrhea duration in the other 6 patients was 4 days. Other GI complaints included abdominal pain (3), nausea (4), and vomiting (3). For NoV treatment, three received oral immunoglobulin, and 8 received Nitazoxanide. Complications included development of concomitant GI-GVHD(5), ileus (2), need for TPN (3), renal failure requiring dialysis (2), ICU stay (3), and death (2). Two patients were co-infected with other enteropathogens such as rotavirus, enteropathogenic and enteroaggregative E.Coli and Clostridioides difficile. Three patients with diarrhea lasting &gt;14 days had serial samples collected over time; NoV shedding lasted 81-546 days. NoV was genotyped in 6 patients(Table 3) and included GII.2(2), GII.4(2), GII.6(1) and GII.12(1). Table 1: Patient characteristics (N=9) Table 2: CAR-T related factors Table 3: NoV Genotypes Conclusion NoV belonging to various genotypes is an important cause of acute and chronic diarrhea in patients receiving CAR-T cell therapy. Disclosures Adilene Olvera, MPH MLS (ASCP), MERK (Grant/Research Support, Scientific Research Study Investigator) Robert L. Atmar, MD, Takeda Vaccines, Inc. (Grant/Research Support) Mary K. Estes, PhD, Takeda Vaccines (Consultant, Grant/Research Support)

Siglec-6 is a novel target for CAR T-cell therapy in acute myeloid leukemia (AML)

Blood ◽  
2021 ◽  
Author(s):  
Hardikkumar Jetani ◽  
Almudena Navarro-Bailón ◽  
Marius Maucher ◽  
Silke Frenz ◽  
Christina Mathilde Verbruggen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
T Cell Therapy ◽  
Hematopoietic Stem ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Novel Target

Acute myeloid leukemia (AML) is attractive for the development of CAR T-cell immunotherapy because AML blasts are susceptible to T-cell-mediated elimination. Here, we introduce sialic-acid-binding immunoglobulin-like lectin (Siglec)-6 as a novel target for CAR T-cells in AML. We designed a Siglec-6-specific CAR with a targeting-domain derived from a human monoclonal antibody JML‑1. We found that Siglec-6 is prevalently expressed on AML cell lines and primary AML blasts, including the subpopulation of AML stem cells. Treatment with Siglec-6-CAR T-cells confers specific anti-leukemia reactivity that correlates with Siglec-6-expression in pre-clinical models, including induction of complete remission in a xenograft AML model in immunodeficient mice (NSG/U937). In addition, we confirmed Siglec-6-expression on transformed B-cells in chronic lymphocytic leukemia (CLL) and show specific anti-CLL-reactivity of Siglec-6-CAR T-cells in vitro. Of particular interest, we found that Siglec-6 is not detectable on normal hematopoietic stem and progenitor cells (HSC/P) and that treatment with Siglec-6-CAR T-cells does not affect their viability and lineage differentiation in colony-formation assays. These data suggest that Siglec-6-CAR T-cell therapy may be used to effectively treat AML without a need for subsequent allogeneic hematopoietic stem cell transplantation. In mature normal hematopoietic cells, we detected Siglec-6 in a proportion of memory (and naïve) B-cells and basophilic granulocytes, suggesting the potential for limited on-target/off-tumor reactivity. The lacking expression of Siglec-6 on normal HSC/P is a key differentiator from other Siglec-family members (e.g. Siglec-3=CD33) and other CAR target antigens, e.g. CD123, that are under investigation in AML and warrants the clinical investigation of Siglec-6-CAR T-cell therapy.

scholarly journals Adoptive T-Cell Therapy to Prevent and Treat Parainfluenza Virus 3 (PIV-3) Infections Post Hematopoietic Stem Cell Transplant (HSCT)

2016 ◽  
Vol 22 (3) ◽  
pp. S138-S139
Author(s):  
Paibel I. Aguayo-Hiraldo ◽  
Ifigeneia Tzannou ◽  
Reuben Arasaratnam ◽  
Nikita Koottiyaniyil ◽  
Manik Kuvalekar ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Cell Therapy ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Adoptive T Cell Therapy ◽  
Parainfluenza Virus ◽  
Cell Transplant ◽  
T Cell Therapy ◽  
Hematopoietic Stem

scholarly journals Humanized Anti-CD19 CAR-T Cell Therapy and Sequential Allogeneic Hematopoietic Stem Cell Transplantation Achieved Long-Term Survival in Refractory and Relapsed B Lymphocytic Leukemia: A Retrospective Study of CAR-T Cell Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Chen ◽  
Yuhan Ma ◽  
Ziyuan Shen ◽  
Huimin Chen ◽  
Ruixue Ma ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Cell Therapy ◽  
Term Survival ◽  
T Cell Therapy ◽  
Hematopoietic Stem ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Early response could be obtained in most patients with relapsed or refractory B cell lymphoblastic leukemia (R/R B-ALL) treated with chimeric antigen receptor T-cell (CAR-T) therapy, but relapse occurs in some patients. There is no consensus on treatment strategy post CAR-T cell therapy. In this retrospective study of humanized CD19-targeted CAR-T cell (hCART19s) therapy for R/R B-ALL, we analyzed the patients treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) or received a second hCART19s infusion, and summarized their efficacy and safety. We retrospectively studied 28 R/R B-ALL patients treated with hCART19s in the Affiliated Hospital of Xuzhou Medical University from 2016 to 2020. After the first hCART19s infusion, 10 patients received allo-HSCT (CART+HSCT group), 7 patients received a second hCART19s infusion (CART2 group), and 11 patients did not receive HSCT or a second hCART19s infusion (CART1 group). The safety, efficacy, and long-term survival were analyzed. Of the 28 patients who received hCART19s treatment, 1 patient could not be evaluated for efficacy, and 25 (92.6%) achieved complete remission (CR) with 20 (74.7%) achieving minimal residual disease (MRD) negativity. Seven (25%) patients experienced grade 3-4 CRS, and one died from grade 5 CRS. No patient experienced ≥3 grade ICANS. The incidence of second CR is higher in the CART+HSCT group compared to the CART2 group (100% vs. 42.9%, p=0.015). The median follow-up time was 1,240 days (range: 709–1,770). Significantly longer overall survival (OS) and leukemia-free survival (LFS) were achieved in the CART+HSCT group (median OS and LFS: not reached, p=0.006 and 0.001, respectively) compared to the CART2 group (median OS: 482; median LFS: 189) and the CART1 group (median OS: 236; median LFS: 35). In the CART+HSCT group, the incidence of acute graft-versus-host disease (aGVHD) was 30% (3/10), and transplantation-related mortality was 30% (3/10). No chronic GVHD occurred. Multivariate analysis results showed that blasts ≥ 20% in the bone marrow and MRD ≥ 65.6% are independent factors for inferior OS and LFS, respectively, while receiving allo-HSCT is an independent factor associated with both longer OS and LFS. In conclusion, early allo-HSCT after CAR-T therapy can achieve long-term efficacy, and the adverse events are controllable.

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