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Article ; Online: Revving the CAR - Combination strategies to enhance CAR T cell effectiveness.

Bansal, Rajat / Reshef, Ran

2020 Volume 45, Page(s) 100695

Abstract: Chimeric antigen receptor (CAR) T cell therapy is currently approved for treatment of refractory B-cell malignancies. Response rates in these diseases are impressive by historical standards, but most patients do not have a durable response and there ... ...

Abstract	Chimeric antigen receptor (CAR) T cell therapy is currently approved for treatment of refractory B-cell malignancies. Response rates in these diseases are impressive by historical standards, but most patients do not have a durable response and there remains room for improvement. To date, CAR T cell activity has been even more limited in solid malignancies. These limitations are thought to be due to several pathways of resistance to CAR T cells, including cell-intrinsic mechanisms and the immunosuppressive tumor microenvironment. In this review, we discuss current experimental strategies that combine small molecules and monoclonal antibodies with CAR T cells to overcome these resistance mechanisms. We describe the biological rationale, pre-clinical data and clinical trials in progress that test the efficacy and safety of these combinations.
MeSH term(s)	Animals ; Clinical Trials as Topic ; Combined Modality Therapy ; Drug Evaluation, Preclinical ; Humans ; Immunomodulation ; Immunotherapy, Adoptive/methods ; Neoplasms/etiology ; Neoplasms/pathology ; Neoplasms/therapy ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/immunology ; Receptors, Chimeric Antigen/immunology ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Treatment Outcome ; Tumor Microenvironment/immunology
Chemical Substances	Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen
Language	English
Publishing date	2020-05-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	639015-8
ISSN	1532-1681 ; 0268-960X
ISSN (online)	1532-1681
ISSN	0268-960X
DOI	10.1016/j.blre.2020.100695
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Zs.A 2207: Show issues

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Article ; Online: Final Outcomes from a Phase 2 Trial of Posoleucel in Allogeneic Hematopoietic Cell Transplant Recipients.

Dadwal, Sanjeet Singh / Bansal, Rajat / Schuster, Michael / Yared, Jean A / Myers, Gary Douglas / Matzko, Michelle Elizabeth / Adnan, Sama / McNeel, David / Ma, Julie / Gilmore, Sarah A / Vasileiou, Spyridoula / Leen, Ann M / Hill, Joshua A / Young, Jo-Anne

Blood advances

2024

Abstract: Allogeneic hematopoietic cell transplantation (allo-HCT) recipients are susceptible to viral infections. We conducted a phase 2 trial evaluating the safety and rate of clinically significant infections (CSIs; viremia requiring treatment or end-organ ... ...

Abstract	Allogeneic hematopoietic cell transplantation (allo-HCT) recipients are susceptible to viral infections. We conducted a phase 2 trial evaluating the safety and rate of clinically significant infections (CSIs; viremia requiring treatment or end-organ disease) following infusion of posoleucel, a partially HLA-matched, allogeneic, off-the-shelf, multivirus-specific T cell investigational product for preventing CSIs with adenovirus, BK virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus-6, or JC virus. This open-label trial enrolled high-risk allo-HCT recipients based on receiving grafts from umbilical cord blood, haploidentical, mismatched, or matched unrelated donors; post-HCT lymphocytes <180/mm3; or use of T cell depletion. Posoleucel dosing was initiated within 15-49 days of allo-HCT and subsequently every 14 days for up to seven doses. The primary endpoint was the number of CSIs due to the six target viruses by week 14. Of the 26 patients enrolled just three (12%) had a CSI by week 14, each with a single target virus. In vivo expansion of functional virus-specific T cells detected via interferon-γ ELISpot assay was associated with viral control. Persistence of posoleucel-derived T cell clones for up to 14 weeks after the last infusion was confirmed by T cell receptor deep-sequencing. Five patients (19%) had acute GVHD grade II-IV. No patient experienced cytokine release syndrome. All six deaths were due to relapse or disease progression. High-risk allo-HCT patients who received posoleucel had low rates of CSIs from six targeted viruses. Repeat posoleucel dosing was generally safe and well tolerated and associated with functional immune reconstitution. www.clinicaltrials.gov NCT04693637.
Language	English
Publishing date	2024-04-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2023011562
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Zs.A 7153: Show issues

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Article ; Online: Outcomes with HLA-matched unrelated donor versus haploidentical hematopoietic cell transplantation.

Mushtaq, Muhammad Umair / Shahzad, Moazzam / Amin, Muhammad K / Lutfi, Forat / DeJarnette, Shaun / Al-Ramahi, Joe S / Li, Kevin / Ahmed, Nausheen / Bansal, Rajat / Abdelhakim, Haitham / Shune, Leyla / Abdallah, Al-Ola / Abhyankar, Sunil H / McGuirk, Joseph P / Singh, Anurag K

Leukemia & lymphoma

2024 Volume 65, Issue 4, Page(s) 493–502

Abstract: We investigated the outcomes after adult haploidentical (haplo) and matched unrelated donor (MUD) hematopoietic cell transplantation (HCT) in a single-center study ( ...

Abstract	We investigated the outcomes after adult haploidentical (haplo) and matched unrelated donor (MUD) hematopoietic cell transplantation (HCT) in a single-center study (
MeSH term(s)	Adult ; Humans ; Unrelated Donors ; Hematopoietic Stem Cell Transplantation/adverse effects ; Cyclophosphamide/therapeutic use ; Graft vs Host Disease/etiology ; Graft vs Host Disease/prevention & control ; Graft vs Host Disease/drug therapy ; Tacrolimus/therapeutic use ; Transplantation Conditioning/adverse effects ; Retrospective Studies
Chemical Substances	Cyclophosphamide (8N3DW7272P) ; Tacrolimus (WM0HAQ4WNM)
Language	English
Publishing date	2024-01-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2023.2300708
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Zs.A 2997: Show issues

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Article: "Waitlist mortality" is high for myeloma patients with limited access to BCMA therapy.

Ahmed, Nausheen / Wesson, William / Mushtaq, Muhammad Umair / Bansal, Rajat / AbdelHakim, Haitham / Bromert, Sarah / Appenfeller, Allison / Ghazal, Batool Abu / Singh, Anurag / Abhyankar, Sunil / Ganguly, Siddhartha / McGuirk, Joseph / Abdallah, Al-Ola / Shune, Leyla

Frontiers in oncology

2023 Volume 13, Page(s) 1206715

Abstract: Background: The first-in-class approved BCMA CAR-T therapy was idecabtagene vicleucel (ide-cel), approved in March 2021, for RRMM patients who progressed after 4 or more lines of therapy. Despite the promising outcomes, there were limited apheresis/ ... ...

Abstract	Background: The first-in-class approved BCMA CAR-T therapy was idecabtagene vicleucel (ide-cel), approved in March 2021, for RRMM patients who progressed after 4 or more lines of therapy. Despite the promising outcomes, there were limited apheresis/production slots for ide-cel. We report outcomes of patients at our institution who were on the "waitlist" to receive ide-cel in 2021 and who could not secure a slot. Methods: We conducted a retrospective review of RRMM patients evaluated at the University of Kansas Cancer Center for ide-cel from 3/2021-7/2021. A retrospective chart review was performed to determine patient and disease characteristics. Descriptive statistics were reported using medians for continuous variables. Survival analysis from initial consult was performed using Kaplan-Meier Survival estimator. Results: Forty patients were eligible and were on the "waitlist" for CAR-T. The median follow-up was 14 months (2-25mo). Twenty-four patients (60%) secured a production slot and 16 (40%) did not. The median time from consult to collection was 38 days (8-703). The median time from collection to infusion was 42 days (34-132 days). The median overall survival was higher in the CAR-T group (NR vs 9 mo, p<0.001). Conclusions: Many patients who were eligible for ide-cel were not able to secure a timely slot in 2021. Mortality was higher in this group, due to a lack of comparable alternatives. Increasing alternate options as well as improvement in manufacturing and access is an area of high importance to improve RRMM outcomes.
Language	English
Publishing date	2023-08-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1206715
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Article ; Online: Antibiotic Exposure, Not Alloreactivity, Is the Major Driver of Microbiome Changes in Hematopoietic Cell Transplantation.

Bansal, Rajat / Park, Heekuk / Taborda, Cristian C / Gordillo, Christian / Mapara, Markus Y / Assal, Amer / Uhlemann, Anne-Catrin / Reshef, Ran

Transplantation and cellular therapy

2021 Volume 28, Issue 3, Page(s) 135–144

Abstract: Both autologous hematopoietic cell transplantation (auto-HCT) and allogeneic hematopoietic cell transplantation (allo-HCT) are associated with significant alterations in the intestinal microbiome. The relative contributions of antibiotic use and ... ...

Abstract	Both autologous hematopoietic cell transplantation (auto-HCT) and allogeneic hematopoietic cell transplantation (allo-HCT) are associated with significant alterations in the intestinal microbiome. The relative contributions of antibiotic use and alloreactivity to microbiome dynamics have not yet been elucidated, however. There is a lack of data on the kinetics of microbiome changes beyond 30 days post-transplantation and how they might differ between different transplantation modalities. A direct comparison of the differential effects of auto-HCT and allo-HCT on the microbiome may shed light on these dynamics. This study was conducted to compare intestinal microbial diversity between auto-HCT recipients and allo-HCT recipients from pre-transplantation to 100 days post-transplantation, and to examine the effect of antibiotics, transplant type (auto versus allo), and conditioning regimens on the dynamics of microbiome recovery. We conducted a longitudinal analysis of changes in the intestinal microbiome in 35 patients undergoing HCT (17 auto-HCT, 18 allo-HCT) at 4 time points: pre-conditioning and 14, 28, and 100 days post-transplantation. Granular data on antibiotic exposure from day -30 pre-transplantation to day +100 post-transplantation were collected. Pre-transplantation, allo-HCT recipients had lower α-diversity in the intestinal microbiome compared with auto-HCT recipients, which correlated with greater pre-transplantation antibiotic use in allo-HCT recipients. The microbiome diversity declined at days +14 and +28 post-transplantation in both cohorts but generally returned to baseline by day +100. Conditioning regimen intensity did not significantly affect post-transplantation α-diversity. Through differential abundance analysis, we show that commensal bacterial taxa involved with maintenance of gut epithelial integrity and production of short-chain fatty acids were depleted after both auto-HCT and allo-HCT. In our dataset, antibiotic exposure was the major driver of post-transplantation microbiome changes rather than alloreactivity, conditioning intensity, or immunosuppression. Our findings also suggest that interventions to limit microbiome injury, such as limiting the use of broad-spectrum antibiotics, should target the pre-transplantation period and not only the peri-transplantation period.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Gastrointestinal Microbiome ; Hematopoietic Stem Cell Transplantation ; Humans ; Transplantation Conditioning ; Transplantation, Homologous/adverse effects
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2021-12-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3062231-1
ISSN	2666-6367
ISSN (online)	2666-6367
DOI	10.1016/j.jtct.2021.12.015
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Zs.A 5082: Show issues

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Article ; Online: A Seemingly Solitary Bone Lesion.

Bansal, Rajat / Rentz, Michael / Law, Jennie Y

JAMA oncology

2016 Volume 2, Issue 6, Page(s) 815–816

MeSH term(s)	Bone Neoplasms/diagnosis ; Bone Neoplasms/diagnostic imaging ; Bone Neoplasms/physiopathology ; Female ; Humans ; Middle Aged
Language	English
Publishing date	2016-06-01
Publishing country	United States
Document type	Case Reports ; Journal Article
ISSN	2374-2445
ISSN (online)	2374-2445
DOI	10.1001/jamaoncol.2016.1068
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Article ; Online: Chimeric antigen receptor T cells for treatment of transformed Waldenström macroglobulinemia.

Bansal, Rajat / Jurcic, Joseph G / Sawas, Ahmed / Mapara, Markus Y / Reshef, Ran

Leukemia & lymphoma

2019 Volume 61, Issue 2, Page(s) 465–468

MeSH term(s)	Aged ; Humans ; Immunotherapy, Adoptive ; Male ; Receptors, Chimeric Antigen/genetics ; T-Lymphocytes ; Waldenstrom Macroglobulinemia/therapy
Chemical Substances	Receptors, Chimeric Antigen
Language	English
Publishing date	2019-09-22
Publishing country	United States
Document type	Case Reports ; Letter
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2019.1665668
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Zs.A 2997: Show issues

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Article ; Online: Predictors of cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation: Insights from a real-world experience.

McGuirk, Matthew / Shahzad, Moazzam / Amin, Muhammad Kashif / Khan, Muhammad Atif / Bellman, Polina / Mudaranthakam, Dinesh Pal / DeJarnette, Shaun / Lutfi, Forat / Ahmed, Nausheen / Bansal, Rajat / Abdelhakim, Haitham / Gorsline, Chelsea / Shoemaker, Dennis Matthew / Abdallah, Al-Ola / Shune, Leyla / Abhyankar, Sunil H / Singh, Anurag K / McGuirk, Joseph P / Mushtaq, Muhammad Umair

Transplant immunology

2024 Volume 84, Page(s) 102039

Abstract: Background: We aimed to investigate factors associated with cytomegalovirus (CMV) viremia and CMV disease and its impact on post-transplant outcomes including overall survival (OS) following allogeneic hematopoietic stem cell transplantation (Allo-SCT).! ...

Abstract	Background: We aimed to investigate factors associated with cytomegalovirus (CMV) viremia and CMV disease and its impact on post-transplant outcomes including overall survival (OS) following allogeneic hematopoietic stem cell transplantation (Allo-SCT). Methods: We conducted a single-center retrospective study including 452 Allo-SCT recipients (matched unrelated donor, MUD 61%; haploidentical, haplo 39%) from 2016 to 2021. Data were analyzed using SPSS v28. Descriptive (chi-square and t-test), Kaplan-Meier and regression analyses were conducted. Results: The median age was 57 years. Sixty-one percent were males and 84.3% were Caucasians. CMV serostatus was positive in 59.1% of recipients. The median follow-up was 24.4 months. CMV viremia and CMV disease were observed in 181 (40%) and 32 (7%) patients, respectively. Among CMV seropositive recipients, 65% developed CMV viremia and 11% were noted to have CMV disease compared to 4% and 1% in seronegative recipients, respectively (p < 0.001). Patients with CMV disease had significantly lower OS than those without CMV disease (median 14.1 months vs. not reached, p = 0.024); however, OS was not associated with CMV viremia (median not reached in both groups, p = 0.640). Letermovir prophylaxis was used in 66% (n = 176/267) of CMV seropositive recipients, but no impact was observed on the incidence of CMV viremia or CMV disease and OS. Conclusions: CMV disease leads to significantly inferior survival after an allogeneic hematopoietic cell transplantation. Recipient CMV seropositive status was associated with the risk of CMV viremia and CMV disease, and this was not abrogated with the use of Letermovir prophylaxis.
Language	English
Publishing date	2024-03-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1160846-8
ISSN	1878-5492 ; 0966-3274
ISSN (online)	1878-5492
ISSN	0966-3274
DOI	10.1016/j.trim.2024.102039
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Zs.A 3784: Show issues

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Article ; Online: Lessons learned from COVID-19 pandemic: outcomes after SARS-CoV-2 infection in hematopoietic cell transplant and cell therapy recipients.

Al-Ramahi, Joe S / Shahzad, Moazzam / Li, Kevin / DeJarnette, Shaun / Chaudhary, Sibgha Gull / Lutfi, Forat / Ahmed, Nausheen / Balusu, Ramesh / Bansal, Rajat / Abdelhakim, Haitham / Shune, Leyla / Singh, Anurag K / Abhyankar, Sunil H / McGuirk, Joseph P / Mushtaq, Muhammad Umair

Leukemia & lymphoma

2023 Volume 64, Issue 12, Page(s) 1981–1991

Abstract: We investigated the outcomes after Coronavirus disease 2019 (COVID) in hematopoietic cell transplant (HCT) or chimeric antigen receptor-T cell (CART) therapy recipients in a single-centre study including all ( ...

Abstract	We investigated the outcomes after Coronavirus disease 2019 (COVID) in hematopoietic cell transplant (HCT) or chimeric antigen receptor-T cell (CART) therapy recipients in a single-centre study including all (
MeSH term(s)	Humans ; Middle Aged ; COVID-19/epidemiology ; COVID-19/therapy ; Hematopoietic Stem Cell Transplantation/adverse effects ; Pandemics ; SARS-CoV-2 ; Transplantation, Homologous ; Transplant Recipients
Language	English
Publishing date	2023-08-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2023.2243355
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Article ; Online: Outcomes of Tyrosine Kinase Inhibitors Maintenance Therapy with or without Allogeneic Hematopoietic Stem Cell Transplantation in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia in First Complete Remission: A Systematic Review and Meta-Analysis.

Shahzad, Moazzam / Hussain, Ali / Tariq, Ezza / Anwar, Iqra / Faisal, Muhammad S / Syed, Leena / Karam, Alvina / Chaudhary, Sibgha Gull / Ahmed, Nausheen / Bansal, Rajat / Khurana, Sharad / Singh, Anurag K / Byrd, Kenneth P / Hematti, Peiman / Abhyankar, Sunil H / McGuirk, Joseph P / Mushtaq, Muhammad Umair

Clinical lymphoma, myeloma & leukemia

2023 Volume 23, Issue 3, Page(s) 178–187

Abstract: We conducted a systematic review and meta-analysis to compare outcomes of tyrosine kinase inhibitor (TKI) maintenance therapy with or without allogeneic hematopoietic stem cell transplantation (HSCT) in Philadelphia chromosome-positive (Ph+) acute ... ...

Abstract	We conducted a systematic review and meta-analysis to compare outcomes of tyrosine kinase inhibitor (TKI) maintenance therapy with or without allogeneic hematopoietic stem cell transplantation (HSCT) in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in first remission (CR1). A literature search was performed on PubMed, Cochrane, and Clinical trials.gov. After screening 1720 articles, 12 studies were included. Proportions and odds ratios (OR) with 95% confidence intervals (CI) were computed. I
MeSH term(s)	Humans ; Tyrosine Kinase Inhibitors ; Philadelphia Chromosome ; Remission Induction ; Hematopoietic Stem Cell Transplantation/methods ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Protein Kinase Inhibitors/therapeutic use
Chemical Substances	Tyrosine Kinase Inhibitors ; Protein Kinase Inhibitors
Language	English
Publishing date	2023-01-12
Publishing country	United States
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Review
ZDB-ID	2540992-X
ISSN	2152-2669 ; 2152-2650
ISSN (online)	2152-2669
ISSN	2152-2650
DOI	10.1016/j.clml.2023.01.002
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