Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cellular Immunotherapy for Refractory Diffuse Large B Cell Lymphoma in the Chimeric Antigen Receptor-Engineered T Cell Era: Still a Role for Allogeneic Transplantation?

ABSTRACT: Chimeric antigen receptor-engineered T (CART) cells are a promising new treatment option for patients with multiply relapsed and refractory (R/R) diffuse large B cell lymphoma (DLBCL). Because of the favorable outcome data reported for CART cells, uncertainty is emerging if there is still a role for allogeneic hematopoietic cell transplantation (allo-HCT) in the treatment of R/R DLBCL. This article provides an overview of available evidence and theoretical considerations to put these 2 types of cellular immunotherapy (CI) into perspective. Altogether, current data suggest that CART cells are preferred now over transplantation as first-choice CI in many clinical situations. However, the majority of patients will fail CART therapy, resulting in an unmet medical need where allo-HCT could be beneficial. In contrast, employing allo-HCT instead of CART cells as first CI should be presently restricted to situations where CART cell therapy is deemed not feasible or useful, such as patients with refractory cytopenia or incipient myelodysplastic syndrome. However, allo-HCT remains a standard treatment option as first CI for patients with chemosensitive R/R DLBCL when CARTs are not available or transplantation is preferred by the patient. Continuous collection and analysis of CI outcome data by professional registries appear to be of key importance for developing rational strategies of CI allocation and sequencing.

SUBMITTER: Dreger P

PROVIDER: S-EPMC7207150 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

A Multidrug-resistant Engineered CAR T Cell for Allogeneic Combination Immunotherapy.

Project description:The adoptive transfer of chimeric antigen receptor (CAR) T cell represents a highly promising strategy to fight against multiple cancers. The clinical outcome of such therapies is intimately linked to the ability of effector cells to engraft, proliferate, and specifically kill tumor cells within patients. When allogeneic CAR T-cell infusion is considered, host versus graft and graft versus host reactions must be avoided to prevent rejection of adoptively transferred cells, host tissue damages and to elicit significant antitumoral outcome. This work proposes to address these three requirements through the development of multidrug-resistant T cell receptor ??-deficient CAR T cells. We demonstrate that these engineered T cells displayed efficient antitumor activity and proliferated in the presence of purine and pyrimidine nucleoside analogues, currently used in clinic as preconditioning lymphodepleting regimens. The absence of TCR?? at their cell surface along with their purine nucleotide analogues-resistance properties could prevent their alloreactivity and enable them to resist to lymphodepleting regimens that may be required to avoid their ablation via HvG reaction. By providing a basic framework to develop a universal T cell compatible with allogeneic adoptive transfer, this work is laying the foundation stone of the large-scale utilization of CAR T-cell immunotherapies.

| S-EPMC4817890 | biostudies-other

Cancer Immunotherapy in Diffuse Large B-Cell Lymphoma.

Project description:Remarkable progress has been made in the field of cancer immunotherapy in the past few years. Immunotherapy has become a standard treatment option for patients with various cancers, including melanoma, lymphoma, and carcinomas of the lungs, kidneys, bladder, and head and neck. Promising immunotherapy approaches, such as chimeric antigen receptor (CAR) T cell therapy and therapeutic blockade of immune checkpoints, in particular cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 pathway (PD-1/PD-L1), have boosted the development of new therapeutic regimens for patients with cancer. Immunotherapeutic strategies for diffuse large B-cell lymphoma (DLBCL) include monoclonal anti-CD20 antibody (rituximab), monoclonal anti-PD-1 antibodies (nivolumab and pembrolizumab), monoclonal anti-PD-L1 antibodies (avelumab, durvalumab, and atezolizumab) and chimeric antigen receptor (CAR) T cell therapy. In this review, we outline the latest highlights and progress in using immunotherapy to treat patients with DLBCL, with a focus on the therapeutic blockade of PD-1/PD-L1 and CAR T cell therapy in DLBCL. We also discuss current clinical trials of PD-1/PD-L1 and CAR T cell therapy and review the challenges and opportunities of using immunotherapy for the treatment of DLBCL.

| S-EPMC6140403 | biostudies-literature

Dual specific CD19/CD22-targeted chimeric antigen receptor T-cell therapy for refractory diffuse large B-cell lymphoma: A case report.

Project description:Clinical trials of chimeric antigen receptors (CARs) targeting CD19 have produced impressive results in hematological malignancies, including diffuse large B-cell lymphoma (DLBCL). However, a notable number of patients with DLBCL fail to achieve remission after CD19 CAR T-cell therapy and may therefore require a dual targeted CAR T-cell therapy. A 31-year-old man with refractory DLBCL was assessed in the present case report. The patient was treated with sequential infusion of single CD19 CAR T cells followed by dual CD19/CD22-targeted CAR T cells. The outcome was that the patient achieved partial remission after the first single CD19 CAR T-cell infusion and complete remission after the dual CD19/CD22-targeted CAR T-cell infusion. Grade 1 cytokine release syndrome (CRS) was observed after the single CD19 CAR T-cell infusion, while grade 3 CRS and hemophagocytic syndrome were observed after the dual targeted CAR T-cell infusion, but these adverse effects alleviated after the treatments. To the best of our knowledge, the present case report is the first to describe the successful application of dual CD19/CD22-targeted CAR T-cell therapy for the treatment of refractory DLBCL. The report suggests that dual CD19/CD22-targeted CAR T-cell therapy may represent a promising option for the treatment of refractory DLBCL; however, caution should be taken due to potential CRS development.

| S-EPMC7405542 | biostudies-literature

Safety and feasibility of chimeric antigen receptor T cell therapy after allogeneic hematopoietic cell transplantation in relapsed/ refractory B cell non-Hodgkin lymphoma.

Project description: Not available

| S-EPMC8224498 | biostudies-literature

Outcomes of primary refractory diffuse large B-cell lymphoma (DLBCL) treated with salvage chemotherapy and intention to transplant in the rituximab era.

Project description:Rituximab-containing salvage chemotherapy followed by high-dose therapy and autologous stem cell transplant (ASCT) in chemosensitive patients remains the standard of care for patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL). However, its role in those patients achieving less than a complete response to first-line therapy (primary refractory disease) in the rituximab era is not well defined. We reviewed the outcomes of 82 transplant-eligible patients with primary refractory DLBCL who underwent salvage therapy with the intent of administering high-dose therapy and ASCT to patients achieving chemosensitive remission. The estimated 3-year overall and progression-free survival for all patients was 38% and 29%, respectively, and 65% and 60% respectively for patients proceeding to stem cell transplant. Long-term remission was achieved in 45% of patients achieving a partial response (PR) to initial induction therapy and <20% of patients with stable or progression of disease following initial therapy. These results suggest that salvage chemotherapy with the intent of subsequent high-dose therapy and ASCT remains a feasible strategy in certain patients with primary refractory DLBCL, particularly for those achieving a PR to frontline therapy. The primary barrier to curative therapy in patients with primary refractory disease is resistance to salvage therapy, and future studies should be aimed towards increasing the response rate in this population.

| S-EPMC5556376 | biostudies-other

Transmission of diffuse large B-cell lymphoma by an allogeneic stem-cell transplant.

Project description: Not available

| S-EPMC6442949 | biostudies-literature

The Role of Allogeneic Stem Cell Transplantation in Relapsed/Refractory Hodgkin's Lymphoma Patients.

Project description:Despite the favorable prognosis of most patients with Hodgkin's Lymphoma (HL), 15-20% of patients remain refractory to chemoradiotherapy, and 20-40% experience relapses following autologous stem cell transplantation (SCT) being used as salvage approach in this situation. Long-term survival of only 20% was reported for patients who failed this option. As some authors suggested the presence of a graft versus HL effect, allogeneic SCT was introduced as a further option. Myeloablative strategies were reported to be able to achieve cure in some younger patients, but high nonrelapse mortality remains a problem. Reduced intensity conditioning, in turn, was found to be associated with high posttransplant relapse rates. As there is currently no standard in the management of HL patients who failed autologous SCT, we here review the literature on allogeneic stem cell transplantation in HL patients with a special focus on the outcomes and risk factors being reported in the largest studies.

| S-EPMC2964008 | biostudies-other

Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

Project description:PurposePatients with transplantation-ineligible relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) fare poorly, with limited treatment options. The antibody-drug conjugate polatuzumab vedotin targets CD79b, a B-cell receptor component.MethodsSafety and efficacy of polatuzumab vedotin with bendamustine and obinutuzumab (pola-BG) was evaluated in a single-arm cohort. Polatuzumab vedotin combined with bendamustine and rituximab (pola-BR) was compared with bendamustine and rituximab (BR) in a randomly assigned cohort of patients with transplantation-ineligible R/R DLBCL (primary end point: independent review committee [IRC] assessed complete response [CR] rate at the end of treatment). Duration of response, progression-free survival (PFS), and overall survival (OS) were analyzed using Kaplan-Meier and Cox regression methods.ResultsPola-BG and pola-BR had a tolerable safety profile. The phase Ib/II pola-BG cohort (n = 27) had a CR rate of 29.6% and a median OS of 10.8 months (median follow-up, 27.0 months). In the randomly assigned cohort (n = 80; 40 per arm), pola-BR patients had a significantly higher IRC-assessed CR rate (40.0% v 17.5%; P = .026) and longer IRC-assessed PFS (median, 9.5 v 3.7 months; hazard ratio [HR], 0.36, 95% CI, 0.21 to 0.63; P < .001) and OS (median, 12.4 v 4.7 months; HR, 0.42; 95% CI, 0.24 to 0.75; P = .002; median follow-up, 22.3 months). Pola-BR patients had higher rates of grade 3-4 neutropenia (46.2% v 33.3%), anemia (28.2% v 17.9%), and thrombocytopenia (41% v 23.1%), but similar grade 3-4 infections (23.1% v 20.5%), versus the BR group. Peripheral neuropathy associated with polatuzumab vedotin (43.6% of patients) was grade 1-2 and resolved in most patients.ConclusionPolatuzumab vedotin combined with BR resulted in a significantly higher CR rate and reduced the risk of death by 58% compared with BR in patients with transplantation-ineligible R/R DLBCL.

| S-EPMC7032881 | biostudies-literature

Novel Therapies for Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

Project description:The most common type of non-Hodgkin lymphoma in adults is diffuse large B-cell (DLBCL). There is a historical unmet need for more effective therapies in the 2nd and 3rd line setting. Emerging immunochemotherapies have shown activity in small studies of heavily pre-treated patients with prolonged remissions achieved in some patients. Anti-CD19 CAR (chimeric antigen receptor) T cells are potentially curative in the 3rd line and beyond setting and are under investigation in earlier lines of therapy. Antibody-drug conjugates (ADC's) such as polatuzumab vedotin targeting the pan-B-cell marker CD79b has proven effectiveness in multiply-relapsed DLBCL patients. Tafasitamab (MOR208) is an anti-CD19 monoclonal antibody producing prolonged remissions when combined with Lenalidomide (LEN) in patients who were not candidates for salvage chemotherapy or autologous stem cell transplant. Selinexor, an oral, small-molecule selective inhibitor of XPO1-mediated nuclear export (SINE), demonstrated prolonged activity against heavily-pretreated DLBCL without cumulative toxicity and is being investigated as part of an oral, chemotherapy-free regimen for relapsed aggressive lymphoma. This article reviews current strategies and novel therapies for relapsed/refractory DLBCL.

| S-EPMC7698117 | biostudies-literature

Non-myeloablative allogeneic hematopoietic stem cell transplantation for adults with relapsed and refractory mantle cell lymphoma: a single-center analysis in the rituximab era.

Project description:Relapsed and refractory (rel/ref) mantle cell lymphoma (MCL) portend a dismal prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only potentially curative therapy in this setting. We analyzed the survival outcomes of 29 recipients of non-myeloablative allo-HSCT for rel/ref MCL, and studied possible prognostic factors in this setting. The cumulative incidences of disease progression and non-relapse mortality at 3 years were 28% (95% confidence interval (CI): 13-46%) and 29% (95% CI: 13-47%), respectively. The cumulative incidence of grade II-IV acute GvHD at days +100 and +180 was 34% (95% CI: 18-52%) and 45% (95% CI: 26-62%), respectively. With a median follow-up in survivors of 53 (range 24-83) months, the 3-year overall survival (OS) and PFS were 54% (95% CI: 38-76%) and 41% (95% CI: 26-64%), respectively. In vivo T-cell depletion with alemtuzumab (n=6) was associated with inferior 3-year PFS (0% vs 51%, P=0.007) and OS (17% vs 64%, P=0.014). Conversely, a second-line international prognostic index (sIPI) at transplantation equal to 0 (no risk factors) was associated with an improved 3-year PFS (52% vs 22%, P=0.020) and OS (71% vs 22%, P=0.006) compared with sIPI ?1. Performing an allo-HSCT before 2007 was associated with a decreased 3-year OS (25% vs 76%, P=0.015) but not with a significantly inferior PFS (17% vs 59%, P=0.058). In this single-center series, we report encouraging results with allo-HSCT for patients with rel/ref MCL. High alemtuzumab doses should probably be avoided in this context.

| S-EPMC4935530 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data