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Lung Cancer Immunotherapy in Transplant Patients and in Patients With Autoimmune Diseases.

ABSTRACT: The use of immune checkpoint inhibitors (ICIs) delivered great and new possibilities in modern treatment of many types of cancers. This therapy based on blockade of such molecules as CTLA-4 (cytotoxic T lymphocyte-associated antigen), PD-1 (programmed cell death receptor type 1), or PD-1 ligand (PD-L1) brings a new hope for patients with non-small cell lung cancer (NSCLC), melanoma, or head and neck squamous carcinoma. Efficacy of immunotherapy was proven in many clinical trials. Unfortunately, ICIs treatment was not addressed to the patients with preexisting allogeneic transplants or autoimmune diseases mainly due to high risk of transplant rejection, exacerbation of autoimmune diseases, and risk of serious toxicity. However, it is possible to receive anti-tumor response to ICIs treatment avoiding graft rejection by adjusting the immunosuppression. Obviously, it depends on the type of transplants: the use of immunotherapy is usually possible in kidney or corneal recipients, but it could be difficult in patients with liver and heart transplant. Therefore, the development of biomarkers for tumor response and transplant rejection in ICIs treated patients is essential. Data coming from published literature support the possibilities of using ICIs in patients with preexisting autoimmune diseases who undergoing proper management of side effects of immunotherapy or when the potential benefits of such treatment outweigh the potential risks. This depends on the type of autoimmune disease and may be difficult or not feasible in patients with systemic lupus erythematosus or systemic sclerosis. Therefore, it may be appropriate to include cancer patients with preexisting autoimmune disease or with allogeneic transplants in clinical trials using immunotherapy when no other effective cancer treatment options exist.

SUBMITTER: Kubiatowski T

PROVIDER: S-EPMC7710966 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Lung Cancer Immunotherapy in Transplant Patients and in Patients With Autoimmune Diseases.

Kubiatowski Tomasz T Nicoś Marcin M Krawczyk Paweł P

Frontiers in oncology 20201119

The use of immune checkpoint inhibitors (ICIs) delivered great and new possibilities in modern treatment of many types of cancers. This therapy based on blockade of such molecules as CTLA-4 (cytotoxic T lymphocyte-associated antigen), PD-1 (programmed cell death receptor type 1), or PD-1 ligand (PD-L1) brings a new hope for patients with non-small cell lung cancer (NSCLC), melanoma, or head and neck squamous carcinoma. Efficacy of immunotherapy was proven in many clinical trials. Unfortunately, ...[more]

PMID: 33330040

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Project description:ImportancePatients with autoimmune disease and lung cancer pose a multidisciplinary treatment challenge, particularly with the advent of immunotherapy. However, the association between autoimmune disease and lung cancer survival is largely unknown.ObjectiveTo determine the association between autoimmune disease and lung cancer survival.Design, setting, and participantsRetrospective cohort study between 2003 and 2019 at a single academic medical center (Northwestern University). A query of the Northwestern Medicine Enterprise Data Warehouse identified 349 patients with lung cancer and several autoimmune diseases. Types of lung cancers included small cell, adenocarcinoma, squamous cell carcinoma, non-small cell not otherwise specified, and large cell carcinoma. Autoimmune diseases included rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, mixed connective tissue disease, myositis, and Sjögren syndrome. Inclusion criteria were biopsy-confirmed lung cancer, autoimmune diagnosis confirmed by a rheumatologist, and death or an encounter listed in the electronic medical record within 2 years of study end. A control group of patients with biopsy-proven lung cancer but without autoimmune disease was identified. Data analysis was conducted from March to July 2020.ExposurePresence of autoimmune disease.Main outcomes and measuresOverall survival and progression-free survival in patients with autoimmune disease. The hypothesis was that patients with autoimmune disease would have worse progression-free survival and overall survival compared with patients in the control group.ResultsOf the original 349 patients, 177 met inclusion criteria. Mean (SD) age at lung cancer diagnosis was 67.0 (10.0) years and 136 (76.8%) were women. Most common autoimmune diseases were rheumatoid arthritis (97 [54.8%]), systemic sclerosis (43 [24.3%]), and systemic lupus erythematous (15 [8.5%]). Most common lung cancers were adenocarcinoma (99 [55.9%]), squamous cell carcinoma (29 [16.4%]), and small cell lung cancer (17 [9.6%]). A total of 219 patients (mean [SD] age at diagnosis, 65.9 [4.1] years; 173 [79.0%]) were identified as having lung cancer without autoimmune disease and included in the control cohort. Compared with patients in the control group, patients with autoimmune disease experienced no difference in overall survival (log-rank P = .69). A total of 126 patients (69.5%) with autoimmune disease received standard of care vs 213 patients (97.3%) in the control group (P < .001). No individual autoimmune disease was associated with worse prognosis, even among patients with underlying interstitial lung disease.Conclusions and relevanceCompared with institutional controls, patients with autoimmune disease experienced no difference in survival despite the fact that fewer patients in this group received standard-of-care treatment. No individual autoimmune disease was associated with worse prognosis. Future multicenter prospective trials are needed to further evaluate autoimmune disease and lung cancer survival.

Project description:Background: Autoimmune cytopenias (AICs) are potentially life-threatening complications following hematopoietic cell transplantation (HCT), yet little is understood about the mechanism by which they develop. We hypothesized that discordant B cell and T cell recovery is associated with AICs in transplant patients, and that this might differ based on transplant indication. Methods: In this case control study of children who underwent HCT at our institution, we evaluated the clinical and transplant characteristics of subjects who developed AICs compared to a control group matched by transplant indication and donor type. In cases, we analyzed the state of immune reconstitution, including B cell recovery, T cell recovery, and chimerism, immediately prior to AIC onset. Subjects were stratified by primary indication for transplant as malignancy (n = 7), primary immune deficiency (PID, n = 9) or other non-malignant disease (n = 4). We then described the treatment and outcomes for 20 subjects who developed AICs. Results: In our cohort, cases were older than controls, were more likely to receive a myeloablative conditioning regimen and had a significantly lower prevalence of chronic GVHD. There were distinct differences in the state of immune recovery based on transplant indication. None of the patients (0/7) transplanted for primary malignancy had T cell recovery at AIC onset compared to 71% (5/7) of patients with PID and 33% (1/3) of patients with non-malignant disease. The subset of patients with PID and non-malignant disease who achieved T cell reconstitution (6/6) prior to AIC onset, all demonstrated mixed or split chimerism. Subjects with AIHA or multi-lineage cytopenias had particularly refractory courses with poor treatment response to IVIG, steroids, and rituximab. Conclusions: These results highlight the heterogeneity of AICs in this population and suggest that multiple mechanisms may contribute to the development of post-transplant AICs. Patients with full donor chimerism may have early B cell recovery without proper T cell regulation, while patients with mixed or split donor chimerism may have residual host B or plasma cells making antibodies against donor blood cells. A prospective, multi-center trial is needed to develop personalized treatment approaches that target the immune dysregulation present and improve outcomes in patients with post-transplant AICs.

Dataset Information

Lung Cancer Immunotherapy in Transplant Patients and in Patients With Autoimmune Diseases.

Publications

Lung Cancer Immunotherapy in Transplant Patients and in Patients With Autoimmune Diseases.

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