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Article ; Online: Anti-CD19 CAR T cell therapy for lymphoma - off to the races!

Maloney, David G

2019 Volume 16, Issue 5, Page(s) 279–280

MeSH term(s)	Adult ; Antigens, CD19 ; Humans ; Immunotherapy, Adoptive ; Lymphoma, Large B-Cell, Diffuse ; Receptors, Antigen, T-Cell
Chemical Substances	Antigens, CD19 ; Receptors, Antigen, T-Cell ; tisagenlecleucel (Q6C9WHR03O)
Language	English
Publishing date	2019-02-27
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2491410-1
ISSN	1759-4782 ; 1759-4774
ISSN (online)	1759-4782
ISSN	1759-4774
DOI	10.1038/s41571-019-0183-7
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Article ; Online: Bortezomib and Vorinostat Therapy as Maintenance Therapy Post Autologous Transplant for Non-Hodgkin's Lymphoma Using R-BEAM or BEAM Transplant Conditioning Regimen.

Holmberg, Leona A / Maloney, David G / Connelly-Smith, Laura

Acta haematologica

2023

Abstract: Introduction: The success of autologous stem cell transplantation (ASCT) for treating non-Hodgkin's lymphoma (NHL) is limited by its high relapse rates. To reduce the risk of relapse, additional maintenance therapy can be added post-transplant. In a non- ...

Abstract	Introduction: The success of autologous stem cell transplantation (ASCT) for treating non-Hodgkin's lymphoma (NHL) is limited by its high relapse rates. To reduce the risk of relapse, additional maintenance therapy can be added post-transplant. In a non-transplant setting at the time of initiation of this study, both bortezomib and vorinostat had been studied alone or in combination for some NHL histology and showed some clinical activity. At our center, this combination therapy post-transplant for Multiple Myeloma (MM) showed acceptable toxicity. Therefore, it seemed reasonable to study this combination therapy post-ASCT for NHL. Methods: NHL patients underwent conditioning for ASCT with rituximab, carmustine, etoposide, cytarabine, melphalan (R-BEAM)/carmustine, etoposide, cytarabine, melphalan (BEAM). After recovery from the acute transplant-related toxicity, combination therapy with IV bortezomib and oral vorinostat (BV) was started and was given for a total of 12 (28-day) cycles. Results: Nineteen patients received BV post ASCT. The most common toxicities were hematologic, gastrointestinal, metabolic, fatigue and peripheral neuropathy. With a median follow-up of 10.3 years, 11 patients (58%) are alive without disease progression and 12 patients (63%) are alive. Conclusions: BV can be given post-ASCT for NHL and produces excellent disease-free and overall survival rates.
Language	English
Publishing date	2023-09-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	80008-9
ISSN	1421-9662 ; 0001-5792
ISSN (online)	1421-9662
ISSN	0001-5792
DOI	10.1159/000533944
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Article ; Online: Immune Therapy for Chronic Lymphocytic Leukemia: Allogeneic Transplant, Chimeric Antigen Receptor T-cell Therapy, and Beyond.

Shadman, Mazyar / Maloney, David G

Hematology/oncology clinics of North America

2021 Volume 35, Issue 4, Page(s) 847–862

Abstract: Despite significant improvement in clinical outcomes of chronic lymphocytic leukemia (CLL), patients who experience failure of Bruton tyrosine kinase inhibitors or venetoclax benefit from immune therapy approaches. Allogeneic transplant is a potentially ... ...

Abstract	Despite significant improvement in clinical outcomes of chronic lymphocytic leukemia (CLL), patients who experience failure of Bruton tyrosine kinase inhibitors or venetoclax benefit from immune therapy approaches. Allogeneic transplant is a potentially curative treatment of CLL but is associated with risk of morbidity and mortality. Although still experimental, chimeric antigen receptor T-cell therapy provides durable remissions in patients with deep molecular responses. This review summarizes the relevant literature and discusses an approach to treatment sequencing and timing of referral for immune therapy. Novel immunotherapy approaches are being investigated and potentially can be utilized in sequence or combination with targeted agents.
MeSH term(s)	Allografts ; Humans ; Immunotherapy, Adoptive ; Leukemia, Lymphocytic, Chronic, B-Cell/therapy ; Receptors, Chimeric Antigen/genetics
Chemical Substances	Receptors, Chimeric Antigen
Language	English
Publishing date	2021-05-28
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	93115-9
ISSN	1558-1977 ; 0889-8588
ISSN (online)	1558-1977
ISSN	0889-8588
DOI	10.1016/j.hoc.2021.03.011
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Article ; Online: Allogeneic Transplantation and Chimeric Antigen Receptor-Engineered T-Cell Therapy for Relapsed or Refractory Mantle Cell Lymphoma.

Gauthier, Jordan / Maloney, David G

Hematology/oncology clinics of North America

2020 Volume 34, Issue 5, Page(s) 957–970

Abstract: Mantle cell lymphoma (MCL) accounts for fewer than 10% of non-Hodgkin lymphoma. There is a high initial response rate to chemotherapy and rituximab, but a nearly universal risk of relapse. Allogeneic hematopoietic cell transplantation (allo-HCT) provides ...

Abstract	Mantle cell lymphoma (MCL) accounts for fewer than 10% of non-Hodgkin lymphoma. There is a high initial response rate to chemotherapy and rituximab, but a nearly universal risk of relapse. Allogeneic hematopoietic cell transplantation (allo-HCT) provides one of the only curative options. We review the role of allo-HCT for relapsed and refractory (R/R) MCL and discuss a novel promising approach using autologous chimeric antigen receptor-engineered T (CAR-T) cells. We review preliminary safety and efficacy data of 2 pivotal trials investigating the use of CD19-targeted CAR-T cells for R/R MCL after ibrutinib failure and discuss potential timing of these approaches.
MeSH term(s)	Hematopoietic Stem Cell Transplantation ; Humans ; Immunotherapy, Adoptive ; Lymphoma, Mantle-Cell/therapy ; Receptors, Chimeric Antigen/therapeutic use ; Transplantation Conditioning ; Transplantation, Homologous
Chemical Substances	Receptors, Chimeric Antigen
Language	English
Publishing date	2020-08-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	93115-9
ISSN	1558-1977 ; 0889-8588
ISSN (online)	1558-1977
ISSN	0889-8588
DOI	10.1016/j.hoc.2020.06.010
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Article: Concomitant EGFR Mutations and ALK Rearrangements in Lung Adenocarcinoma Treated With Osimertinib.

Thomas, David / Maloney, McKenzie E / Raval, Girindra

Cureus

2023 Volume 15, Issue 11, Page(s) e48122

Abstract: Lung cancer is the third most common cancer in addition to being the cancer responsible for the most annual deaths in the United States, comprising 15% of all diagnosed cancers, and 28% of all cancer deaths in 2020. Major advances in survival are because ...

Abstract	Lung cancer is the third most common cancer in addition to being the cancer responsible for the most annual deaths in the United States, comprising 15% of all diagnosed cancers, and 28% of all cancer deaths in 2020. Major advances in survival are because of gene sequencing and the advent of targeted biological therapy. The prevalence of epidermal growth factor receptor (EGFR) mutations coexisting with anaplastic lymphoma kinase (ALK) rearrangements is quite low. However, the clinical relevance and effective treatment of these cancers require further investigation. This case series describes two patients diagnosed with stage IV adenocarcinoma with coexisting EGFR and ALK rearrangements. In Case 1, a 73-year-old male presented with worsening ataxia and headaches. In Case 2, a 64-year-old female presented with worsening dyspnea. Molecular studies revealed ALK gene fusion and the L861Q EGFR mutation in Case 1 and L858R EGFR mutation and ALK gene fusion in Case 2. Both patients received a gamma knife and an EGFR-tyrosine kinase inhibitor (TKI), osimertinib. In one of the cases, following the discovery of new brain metastases, the dose of osimertinib was increased from 80 to 160 mg. The patient passed away nine months after beginning EGFR-TKI treatment, one month after increasing the dose. The second patient experienced a significant interval reduction in the size of enhancing metastasis in both the right frontal and left parietal lobe after four months of EGFR-TKI treatment. The cases of coexisting EGFR mutations and ALK rearrangements are quite rare, and treatment can be challenging. Here, EGFR-TKI had a mixed response among our patients.
Language	English
Publishing date	2023-11-01
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.48122
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Article ; Online: Answering the "Doctor, can CAR-T therapy cause cancer?" question in clinic.

Banerjee, Rahul / Poh, Christina / Hirayama, Alexandre V / Gauthier, Jordan / Cassaday, Ryan D / Shadman, Mazyar / Cowan, Andrew J / Till, Brian G / Green, Damian J / Kiem, Hans-Peter / Gopal, Ajay K / Maloney, David G

Blood advances

2024 Volume 8, Issue 4, Page(s) 895–898

MeSH term(s)	Humans ; Receptors, Chimeric Antigen ; Immunotherapy, Adoptive/adverse effects ; Neoplasms/etiology ; Neoplasms/therapy ; Physicians
Chemical Substances	Receptors, Chimeric Antigen
Language	English
Publishing date	2024-01-10
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.2023012336
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Article ; Online: Health State Utilities for Adverse Events Associated with Chimeric Antigen Receptor T-Cell Therapy in Large B-Cell Lymphoma.

Howell, Timothy A / Matza, Louis S / Jun, Monika P / Garcia, Jacob / Powers, Annette / Maloney, David G

PharmacoEconomics - open

2022 Volume 6, Issue 3, Page(s) 367–376

Abstract: Background: Chimeric antigen receptor (CAR) T-cell therapy provides effective treatment for large B-cell lymphoma (LBCL). Cost-utility analyses examining and comparing the value of these treatments require health state utilities representing key ... ...

Abstract	Background: Chimeric antigen receptor (CAR) T-cell therapy provides effective treatment for large B-cell lymphoma (LBCL). Cost-utility analyses examining and comparing the value of these treatments require health state utilities representing key characteristics to differentiate among therapies. This study estimated utilities for adverse events (AEs) associated with CAR T-cell therapy, including cytokine release syndrome (CRS) and neurological events (NEs). Methods: Health state vignettes were drafted based on literature review, AE reports from a trial of CAR T-cell therapy, and clinician input. Health states were valued in time trade-off interviews with general population participants in the UK. The first vignette described relapsed/refractory LBCL treated with CAR T-cell therapy without AEs. Five other vignettes had the same LBCL and treatment description, with the addition of an AE. Disutilities (i.e., utility decrease) associated with these AEs were calculated by subtracting the utility of the health state without AEs from those of the other health states. Results: Interviews were completed with 218 participants (50% male; mean age 49 years). Mean (standard deviation [SD]) utility for CAR T-cell therapy without AEs was 0.73 (0.30). Mean (SD) disutilities associated with CRS were -0.01 (0.04) for grade 1, -0.05 (0.09) for grade 2, and -0.23 (0.24) for grade 3/4. Mean (SD) disutilities associated with NEs were -0.04 (0.07) for grade 1/2 and -0.18 (0.22) for grade 3/4. Conclusions: More severe AEs were associated with greater disutilities. Health state utilities estimated in this study may be useful in cost-effectiveness models examining the value of CAR T-cell therapy in patients with LBCL.
Language	English
Publishing date	2022-02-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2874287-4
ISSN	2509-4254 ; 2509-4262
ISSN (online)	2509-4254
ISSN	2509-4262
DOI	10.1007/s41669-021-00316-0
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Article ; Online: Molecular detection and characterization of Blastocystis in herbivore livestock species in Portugal.

Figueiredo, Ana M / Santín, Mónica / Köster, Pamela C / Dashti, Alejandro / Maloney, Jenny G / Torres, Rita T / Fonseca, Carlos / Mysterud, Atle / Carvalho, João / Hipólito, Dário / Rossa, Mariana / Palmeira, Josman D / González-Barrio, David / Calero-Bernal, Rafael / Carmena, David

Veterinary parasitology

2024 Volume 327, Page(s) 110147

Abstract: Blastocystis is a ubiquitous intestinal protist in humans and animals worldwide. The traditional livestock free-roaming raising system in rural communities increases the risk of infection with contact with a wider range of pathogens transmitted via the ... ...

Abstract	Blastocystis is a ubiquitous intestinal protist in humans and animals worldwide. The traditional livestock free-roaming raising system in rural communities increases the risk of infection with contact with a wider range of pathogens transmitted via the faecal-oral route associated with that wildlife-livestock-human interface. However, no studies have been conducted to determine the occurrence and subtype distribution of Blastocystis in livestock in Portugal. Here, we collected 180 faecal samples from herbivore livestock (cattle, goats, horses, and sheep) in different regions of the country to investigate Blastocystis prevalence and subtype diversity using PCR and next-generation amplicon sequencing. Blastocystis was present in 40.6% (73/180; 95% CI: 33.31-48.11) of the samples (goats, 81.0%; sheep, 60.9%; cattle, 32.2%). None of the horse samples were Blastocystis-positive. Eighteen subtypes were detected (ST1-ST3, ST5-ST7, ST10, ST13, ST14, ST21, ST23-ST26, ST30, ST42-ST44). Mixed infections were detected in 97.3% of the Blastocystis-positive samples. Potentially zoonotic subtypes were identified in 75.0%, 96.4%, and 100% of the Blastocystis-positive specimens collected from cattle, sheep, and goats, respectively. These results demonstrate that cattle, sheep, and goats harbour a high diversity of Blastocystis subtypes in the study regions. Importantly, our data provide novel molecular evidence strongly suggesting that some Blastocystis STs/ST subgroups may have differential host specificity.
MeSH term(s)	Animals ; Humans ; Cattle ; Horses ; Sheep ; Blastocystis/genetics ; Blastocystis Infections/epidemiology ; Blastocystis Infections/veterinary ; Livestock ; Portugal/epidemiology ; Herbivory ; Goats ; Feces ; Prevalence ; Genetic Variation ; Phylogeny ; Cattle Diseases ; Goat Diseases/epidemiology ; Horse Diseases ; Sheep Diseases/epidemiology
Language	English
Publishing date	2024-02-12
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	196831-2
ISSN	1873-2550 ; 0304-4017
ISSN (online)	1873-2550
ISSN	0304-4017
DOI	10.1016/j.vetpar.2024.110147
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Article ; Online: Anti-CD20 antibody therapy for B-cell lymphomas.

Maloney, David G

The New England journal of medicine

2012 Volume 366, Issue 21, Page(s) 2008–2016

MeSH term(s)	Antibodies, Monoclonal, Murine-Derived/adverse effects ; Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Antigens, CD20/immunology ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cyclophosphamide/therapeutic use ; Doxorubicin/therapeutic use ; Humans ; Lymphoma, B-Cell/drug therapy ; Male ; Middle Aged ; Practice Guidelines as Topic ; Prednisone/therapeutic use ; Rituximab ; Vincristine/therapeutic use
Chemical Substances	Antibodies, Monoclonal, Murine-Derived ; Antigens, CD20 ; Antineoplastic Agents ; Rituximab (4F4X42SYQ6) ; Vincristine (5J49Q6B70F) ; Doxorubicin (80168379AG) ; Cyclophosphamide (8N3DW7272P) ; Prednisone (VB0R961HZT)
Language	English
Publishing date	2012-05-24
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMct1114348
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Article ; Online: Clinical trials of CD19-targeted CAR-modified T cell therapy; a complex and varied landscape.

Turtle, Cameron J / Maloney, David G

Expert review of hematology

2016 Volume 9, Issue 8, Page(s) 719–721

MeSH term(s)	Antigens, CD19 ; Cell- and Tissue-Based Therapy ; Clinical Trials as Topic ; Humans ; Immunotherapy, Adoptive ; Receptors, Antigen, T-Cell ; Recoverin
Chemical Substances	Antigens, CD19 ; RCVRN protein, human ; Receptors, Antigen, T-Cell ; Recoverin (135844-11-0)
Language	English
Publishing date	2016-07-04
Publishing country	England
Document type	Editorial ; Research Support, Non-U.S. Gov't
ZDB-ID	2516804-6
ISSN	1747-4094 ; 1747-4086
ISSN (online)	1747-4094
ISSN	1747-4086
DOI	10.1080/17474086.2016.1203251
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