P08.01 Immune-Related Acute Motor Axonal Neuropathy: A Small Case Series and Review of the Literature

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii26-ii26
Author(s):  
Y Pina ◽  
N Tran ◽  
P Forsyth ◽  
S Mokhtari ◽  
E Peguero
Keyword(s):  
Checkpoint Inhibitors ◽  
Axonal Neuropathy ◽  
Case Series ◽  
Standard Of Care ◽  
Cancer Center ◽  
High Dose ◽  
Acute Motor Axonal Neuropathy ◽  
First Case ◽  
Oncological Patients ◽  
Solid Malignancies

Abstract BACKGROUND Immunotherapy have revolutionized cancer treatment in the past decade, with a significant increased survival in patients with solid tumors. However, the use of immune checkpoint inhibitors (ICIs) has been associated with a growing number of neurotoxicities, some of which can be fatal if not recognized and treated promptly. Some of these neurotoxicities include very uncommon syndromes like Acute Motor Axonal Neuropathy (AMAN). Herein we present four oncological cases of patients who underwent immunotherapy and developed AMAN. METHODS Four patients were diagnosed with immune-related AMAN between 2017 and 2000 at H. Lee Moffitt Cancer Center. The patients were treated with standard of care and currently follow up in clinic. RESULTS We describe four oncological patients who developed a motor axonal neuropathy (i.e., AMAN) confirmed on nerve conduction studies following 2 cycles of immunotherapy, including a 28 year old woman with melanoma brain metastasis and a 50 year old woman with renal cell carcinoma both treated with ipilimumab and nivolumab, a 32 year old man with Hodgkin lymphoma who was treated with nivolumab and brentuximab, and a 77 year old woman with renal urothelial cancer who was treated with pembrolizumab and cabozantinib. All four patients were promptly recognized as having immune-related neurotoxicity (irNs), were promptly treated (i.e., high dose steroids +/- IVIG +/- other immunomodulators), and significantly improved and have remained stable. CONCLUSION This is the first case series of patients with AMAN following two cycles of immunotherapy, who were successfully treated. It is crucial to develop a better understanding of the irNs associated with ICIs, including those rare conditions that are difficult to diagnose and treat, as the utilization of these immunomodulating therapies continues to increase and expand to include other solid malignancies. Neurologists should be involved early on in any case of suspected irN to assist in the management of these complicated patients and a swift work up should be initiated for timely diagnosis and treatment.

NCMP-21. IMMUNE-RELATED ACUTE MOTOR AXONAL NEUROPATHY: A SMALL CASE SERIES AND REVIEW OF THE LITERATURE

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi151-vi151
Author(s):  
Yolanda Pina ◽  
Nam Tran ◽  
Neha Verma ◽  
Michael Vogelbaum ◽  
Peter Forsyth ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Axonal Neuropathy ◽  
Case Series ◽  
Standard Of Care ◽  
Cancer Center ◽  
High Dose ◽  
Acute Motor Axonal Neuropathy ◽  
First Case ◽  
Oncological Patients ◽  
Solid Malignancies

Abstract BACKGROUND Immunotherapy revolutionized cancer treatment in the past decade, with a significant increased survival in patients with solid tumors. However, immune checkpoint inhibitors (ICIs) have been associated with a growing number of neurotoxicities, some of which can be fatal if not recognized and treated promptly. Some of these neurotoxicities include very uncommon syndromes like Acute Motor Axonal Neuropathy (AMAN). Herein we present four oncological cases of patients who underwent immunotherapy and developed AMAN. METHODS Four patients were diagnosed with immune-related AMAN between 2017 and 2000 at H. Lee Moffitt Cancer Center. Patients were treated with standard of care. RESULTS We describe four oncological patients who developed a motor axonal neuropathy (i.e., AMAN) confirmed on nerve conduction studies following 2 cycles of immunotherapy, including a 28 year old woman with melanoma brain metastasis and a 50 year old woman with renal cell carcinoma both treated with ipilimumab and nivolumab, a 32 year old man with Hodgkin lymphoma who was treated with nivolumab and brentuximab, and a 77 year old woman with renal urothelial cancer who was treated with pembrolizumab and cabozantinib. All four patients were promptly recognized as having immune-related neurotoxicity (irNs), were promptly treated (i.e., high dose steroids +/- IVIG +/- other immunomodulators), and significantly improved and have remained stable. CONCLUSION This is the first case series of patients with AMAN following two cycles of immunotherapy, who were successfully treated. It is crucial to develop a better understanding of irNs, including those rare conditions that are difficult to diagnose and treat, as the utilization of these immunomodulating therapies continues to expand to include other solid malignancies. Neurologists should be involved early on in any case of suspected irN to assist in the management of these complicated patients and a swift work up should be initiated for timely diagnosis and treatment.

Management Of Immunotherapy Adverse Events In Oncological Patients: Anti-Ctla-4, Anti-Pd-1/Pd-L1

2020 ◽  
Vol 15 ◽  
Author(s):  
Mattia Brigida ◽  
Alessia Perricelli ◽  
Fausto Sposato ◽  
Maria Giovanna Spadafora ◽  
Angelo Pomillo ◽  
...  
Keyword(s):  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Corticosteroid Treatment ◽  
High Dose ◽  
Emergency Setting ◽  
Serious Adverse Events ◽  
Oncological Patients ◽  
Grade Ii ◽  
Dose Corticosteroid

Background: The widespread use of immunotherapy drugs in the oncological field has led to the spread of new toxicities compared to the more common chemotherapy treatments. This is because immunotherapy with anti-CTLA-4 (Cytotoxic T Lymphocytes-Associated Antigen 4), anti-PD-1 and anti-PD-L1 monoclonal antibodies has become the standard-of-care in a growing number of indications. Any organ or tissue can be involved, but more commonly side effects are reported regarding skin, colon, endocrine glands, liver, lung and kidney. Other less frequent, but more serious, adverse events are neurological and myocarditis. Methods: We performed an electronic search on PUBMED of the literature concerning immunotherapy-related toxicities and their management in oncological patients from 2007 to 2020, with particular attention to the most recent publications. Aim: To summarize the different types of immunotherapy-related toxicities, together with their incidence and diagnosis, and to simplify their management, especially in the emergency setting. Conclusion: Usually, for grade I toxicities it is not recommended to stop immunotherapy; for most of grade II toxicities, immunotherapy should be postponed to when toxicity will have regressed to grade I, considering the possibility of a corticosteroid treatment for most of toxicities. The majority of grade III and IV require administration of high-dose corticosteroid intravenous therapy and suspension of immunotherapy. Mortality related to immune checkpoint inhibitors’ toxicity, occurring at a rate of 0.3-1.3%, is well below fatality rates due to other oncologic interventions and should not discourage the promising results so far reached by immunotherapy.

scholarly journals NCMP-23. PEMBROLIZUMAB-ASSOCIATED CD8+ VASCULITIC MONONEURITIS MULTIPLEX IN A PATIENT WITH MESOTHELIOMA: FIRST CASE REPORT

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii127-ii127
Author(s):  
Michaela Baldauf ◽  
Kapauer Monika ◽  
Jörger Markus ◽  
Flatz Lukas ◽  
Regulo Rodriguez ◽  
...  
Keyword(s):  
Case Report ◽  
Checkpoint Inhibitors ◽  
Axonal Neuropathy ◽  
Immunosuppressive Treatment ◽  
Small Vessel ◽  
Small Vessel Vasculitis ◽  
High Dose ◽  
Mononeuritis Multiplex ◽  
First Case ◽  
The Right

Abstract INTRODUCTION Immunotherapy, especially with immune checkpoint inhibitors (ICPI), has increasingly become an attractive treatment modality for various types of cancers. However, many patients develop ICPI-associated autoimmune adverse events such as pneumonitis, colitis or rarely neurological syndromes. Large and medium vessel vasculitis haS only occasionally been reported. Here we report the first case of ICPI-associated mononeuritis multiplex in a patient with malignant mesothelioma, caused by a histological proven small vessel vasculitis. CASE REPORT A 61-year old female developed subacute progressive painful and asymmetric sensorimotor deficits on distal extremities. Electrophysiologically, signs of a severe axonal neuropathy of both legs and the right arm were found, and swellings of the corresponding nerves were seen upon nerve ultrasound exam. The clinical and electrophysiological findings were reminiscent of mononeuritis multiplex. Laboratory work up including CSF examination was normal. More than two years prior to developing peripheral nerve deficits, the patient had been diagnosed with malignant pleural mesothelioma and treated with the anti-PD1 monoclonal antibody pembrolizumab on progression after chemotherapy. Biopsy of the right sural nerve revealed a small vessel vasculitis with a lymphocyte predominance of CD8+ T cells over CD4+ T as well as B lymphocytes. Despite discontinuation of pembrolizumab and immunosuppressive treatment (high dose methylprednisone, cyclophosphamide) complemented by opioid therapy, painful allodynia persisted. CONCLUSION ICPI-associated autoimmune disorders also include small vessel vasculitis with rare phenotypes such as mononeuritis multiplex. Further studies are required to improve our understanding of the link between ICPIs, and the pathogenic process leading to vasculitis, as well as to optimize treatment options for those rare diseases.

scholarly journals Acute motor axonal neuropathy after ipilimumab and nivolumab treatment in melanoma brain metastases: A case report and review of the literature

2021 ◽  
Vol 9 ◽  
pp. 2050313X2110422
Author(s):  
Yolanda Piña ◽  
Brittany R. Evernden ◽  
Nikhil Khushalani ◽  
Kim Margolin ◽  
Hussein Tawbi ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Axonal Neuropathy ◽  
Braf V600e ◽  
Acute Motor Axonal Neuropathy ◽  
Melanoma Brain Metastasis ◽  
First Case

The use of immune checkpoint inhibitors including ipilimumab and nivolumab has expanded for several tumors including melanoma brain metastasis. These have resulted in a growing spectrum of neurologic immune-related adverse events, including ones that are rare and difficult to diagnose and treat. Here, we present a patient with melanoma brain metastasis who was treated with immune checkpoint inhibitors and developed an Acute Motor Axonal Neuropathy. To our knowledge, this is the first case of Acute Motor Axonal Neuropathy as an immune-related adverse event associated with combination treatment of ipilimumab and nivolumab, who was successfully treated. A 28-year-old woman with metastatic BRAF V600E melanoma developed melanoma brain metastasis and was enrolled on Checkmate 204, a Phase 2 clinical trial using ipilimumab (3 mg/kg intravenous) and nivolumab (1 mg/kg intravenous) every 3 weeks for four cycles, followed by monotherapy with nivolumab (240 mg intravenous) every 2 weeks. A few days after Cycle 2 of ipilimumab and nivolumab, she developed a pure motor axonal neuropathy consistent with Acute Motor Axonal Neuropathy. She was treated with several immunosuppressive treatments including high dose methylprednisolone, immune globulin, and infliximab, and her motor neuropathy eventually improved several months after onset of symptoms. Unfortunately, she had progression of her systemic disease and died several months later. This is the first case reported of Acute Motor Axonal Neuropathy associated with ipilimumab and nivolumab, successfully treated with immune-suppressive therapy. As the field of immunotherapy expands with the increasing use of the immune checkpoint inhibitors, it is critical to increase our knowledge and understanding of the neurologic immune-related adverse events associated with immune checkpoint inhibitors. This includes the spectrum of rare neurologic immune-related adverse events, which can be quite difficult to recognize and treat. Early consultations with neurology may expedite a diagnosis and treatment plan in patients with unexplained weakness receiving immune checkpoint inhibitor therapy.

scholarly journals Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma

2020 ◽  
Vol 8 (2) ◽  
pp. e001009
Author(s):  
Sara Bedrose ◽  
Kevin Charles Miller ◽  
Lina Altameemi ◽  
Mohamed S Ali ◽  
Sameh Nassar ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Salvage Therapy ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Case Series ◽  
Progression Free Survival ◽  
Adrenal Cortical Carcinoma ◽  
Retrospective Case ◽  
First Case ◽  
Platinum Based Chemotherapy

BackgroundThere is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC.MethodsA retrospective case series describing the use of LEN/PEM as salvage therapy in patients with progressive/metastatic ACC.ResultsEight patients were treated with the LEN/PEM combination therapy. Half were female, and the median age at time of diagnosis was 38 years (range 21–49). Three (37.5%) patients had hormonally active ACC. The median number of prior lines of systemic therapy was 4 (range 2–9). Six (75%) patients had had disease progression on prior CPIs and five (62.5%) patients had progressed on prior MKI therapy. The median progression-free survival was 5.5 months (95% CI 1.8–not reached) and median duration of therapy was 8.5 months (range 2–22). Two (25%) patients had a partial response, one (12.5%) patient had stable disease, and five (62.5%) patients had progressive disease. None of the eight patients stopped therapy because of adverse events.ConclusionsIn our small cohort of heavily pretreated patients with ACC, the combination of LEN/PEM was associated with objective responses in a subset of patients without significant toxicity. This combination should be formally investigated in phase II clinical trial with robust correlative studies to identify predictors for response.

scholarly journals P1693LONG-TERM OUTCOME OF KIDNEY TRANSPLANTATION IN PLASMA CELLS DYSCRASIAS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Fulvia Zappulo ◽  
Gabriele Donati ◽  
Giorgia Comai ◽  
Claudia Bini ◽  
Andrea Angeletti ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Light Chain ◽  
Graft Failure ◽  
Case Series ◽  
University Hospital ◽  
High Dose ◽  
Light Chain Deposition Disease ◽  
Light Chain Amyloidosis ◽  
First Case

Abstract Background and Aims Survival of patients with Multiple Myeloma (MM), Light Chain Amyloidosis (LCA) and Monoclonal Gammopathies of renal significance (MGRS) on chronic renal replacement therapy (RRT) is poor. The gold standand treatment of plasma cell dyscrasias (PCD) is high-dose chemotherapy followed by Autologous Stem Cell Transplantation (ASCT) which can induce complete remission and longer survival than chemotherapy alone. Kidney transplantation (KT) after ASCT could represent an option for patients with PCD and End Stage Renal Disease (ESRD). There is no evidence about the time of follow up required from MM remission and KT. Method We present a case series of 5 patients who underwent KT after ASCT and remission of MM among 2,500 transplant recipients followed at the Nephrology Dialysis and Renal Transplantation Unit of S.Orsola University Hospital from 1967 untill now. As in case of recovery from solid cancers, the feasibility of KT after MM was considered when no signs of relapse were assessed. In our cohort 3 patients were affected by Light Chain Deposition Disease (LCDD), 1 patient presented Myeloma Cast Nephropathy (MCN) and one patient Light Chain Amyloidosis (LCA). They all required RRT and underwent KT after ASCT. Results Time between ASCT and KT ranged from 3 and 11 years and clinical outcome was very different. The mean follow up period ranged from 2 to 4 years. In the first case (LCDD) KT was performed 11 years after ASCT, the graft failure occurred 6 years later because of chronic allograft nephropathy requiring RRT. In the second case (LCDD) patient received KT 3 years after ASCT. He developed Bence-Jones proteinuria requiring specific therapy with Dexametasone and Bortezomib determining progressive graft failure. In the third case (LCDD) KT was performed 4 years after ASCT and the 4 year follow up is negative for relapse of MM or ESRD. The fourth patient presented MCN and received KT 8 years after ASCT. MCN relapsed 6 years later; it caused ESRD requiring RRT. In the last patient (LCA) KT was performed 4 years after ASCT. No recurrence occurred in a 2-year follow up. Conclusion MM is the most frequent malignancy in dialytic population; the need for KT in MM remains high. ASCT improves the quality of life and offers higher survival in patients with myeloma/MGRS/amyloidosis-related ESRD. Therefore the combination of chemotherapy/ASCT and KT is pivotal to pursue renal restoring. Since high risk of recurrence larger study are required to clarify the better follow up period after MM remission and KT.

Endovascular intervention for acute stroke due to infective endocarditis

2012 ◽  
Vol 32 (2) ◽  
pp. E1 ◽  
Author(s):  
Haitham Dababneh ◽  
V. Shushrutha Hedna ◽  
Jenna Ford ◽  
Ziad Taimeh ◽  
Keith Peters ◽  
...  
Keyword(s):  
Infective Endocarditis ◽  
Acute Stroke ◽  
Case Reports ◽  
Case Series ◽  
Standard Of Care ◽  
Clinical Decision ◽  
Neurological Complications ◽  
Endovascular Interventions ◽  
First Case ◽  
Risk Of Hemorrhage

The overall incidence of neurological complications due to infective endocarditis is as high as 40%, with embolic infarcts more common than hemorrhagic strokes. The standard of care for typical strokes does not apply to infective endocarditis because there is a substantial risk of hemorrhage with thrombolysis. In the last decade there have been multiple case reports of intravenous and intraarterial thrombolysis with successful outcomes for acute strokes with related infective endocarditis, but successful endovascular interventions for acute strokes associated with infective endocarditis are rarely reported. To the authors' knowledge, this report is the first case in the literature to use a mechanical retrieval device in successful vegetation retrieval in an infective endocarditis acute stroke. Although an interventional approach for treatment of acute stroke related to infective endocarditis is a promising option, it is controversial and a cautious clinical decision should be made on a case-by-case basis. The authors conclude that this approach can be tested in a case series with matched controls, because this condition is rare and a randomized clinical trial is not a realistic option.

032 Neurological sequelae of immune checkpoint inhibitors: a case series

2018 ◽  
Vol 89 (6) ◽  
pp. A13.3-A14 ◽  
Author(s):  
Matthew Silsby ◽  
Stephen R Duma ◽  
Neil Mahant ◽  
Steve Vucic ◽  
Andrew Henderson
Keyword(s):  
T Cells ◽  
Checkpoint Inhibitors ◽  
Early Recognition ◽  
Case Series ◽  
Tumour Response ◽  
Stage Iv ◽  
High Dose ◽  
Solid Organ ◽  
Fisher Syndrome ◽  
Neurological Sequelae

IntroductionMonoclonal antibodies directed against co-stimulatory molecules on T cells (checkpoint inhibitors, CIs) are used to treat solid organ malignancies. Neurological complications are an increasingly recognised consequence of their use. We present three patients referred to the Neurology service at Westmead Hospital in 2017 with new neurological complaints following CI therapy.CasesPatient 1, a 54 year old woman with stage IV non-small cell lung cancer treated with pembrolizumab (anti-PD-1), presented with cerebral vasculitis causing bilateral ACA territory cerebral infarction. Patient 2, a 59 year old woman with metastatic melanoma treated with ipilimumab (anti-CTLA4) and nivolumab (anti-PD-1), presented with ataxia, diplopia and ptosis consistent with Miller Fisher syndrome. Patient 3, a 77 year old woman with metastatic colorectal adenocarcinoma treated with nivolumab (anti-PD-1), presented with ocular myasthenia manifesting as fatigable ptosis and complex ophthalmoplegia.The diagnoses were made by clinical assessment with imaging and neurophysiological investigations where possible. Antibodies relevant to the neurological condition were negative, in keeping with previous reports. CIs were discontinued in all patients. Treatment included intravenous pulsed methylprednisolone followed by high dose oral taper in all patients. Additionally, Patient 1 was treated with infliximab and rituximab; Patients 2 and 3 received intravenous immunoglobulin followed by monthly maintenance therapy; Patient 2 underwent plasma exchange. Patients 1 and 2 recovered independent ambulation. Patient 3 died two months after presentation due to underlying malignancy.ConclusionCheckpoint inhibitors block co-stimulatory molecules on T-cells, allowing the immune system to mount an anti-tumour response. The resulting immune dysregulation can also lead to organ-specific inflammatory and immune complications, of which neurological sequelae are increasingly recognised. The three reported patients highlight the spectrum of disease that can arise. Their occurrence within one year suggests an increasing incidence, and a need for increased vigilance. Early recognition is paramount as treatment with high dose corticosteroids, even in conditions that would not normally respond, is recommended.

scholarly journals Neuromuscular Complications of Targeted Anticancer Agents: Can Tyrosine Kinase Inhibitors Induce Myasthenia Gravis? Getting Answers From a Case Report up to a Systematic Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Dimitrios C. Ziogas ◽  
Dimitrios Mandellos ◽  
Charalampos Theocharopoulos ◽  
Panagiotis-Petros Lialios ◽  
Spyros Bouros ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Myasthenia Gravis ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Braf Inhibitor ◽  
First Case ◽  
Long Term Treatment ◽  
Neuromuscular Complications

More than 40 tyrosine kinase inhibitors (TKIs) have received hematological or oncological indications over the past 20 years, following the approval of imatinib, and many others are currently being tested in clinical and preclinical level. Beyond their common toxicities, no certain agent from this large class of molecularly targeted therapies was strongly associated with “off-target” impairment of neuromuscular transmission, and although myasthenia gravis (MG) is a well-characterized autoimmune disorder, only few sporadic events proven by serologically detected causative autoantibodies and/or by positive electrophysiological tests are reported in the literature. Herein, we present the first case of anti-MUSK (+) MG in a woman with metastatic BRAF-mutant melanoma after long-term treatment with dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor). Triggered by this report, a systematic literature review was conducted, summarizing all other cancer cases that developed MG, after exposure to any type of targeted agent and regardless of the underlying malignancy. All available data on the clinical diagnosis, the potential of administered TKIs to induce a seropositive myasthenic syndrome, the immune and non-immune-mediated pathogenesis of postsynaptic damage, and the challenging management of this neuromuscular toxicity were collected and discussed. In the presented case, MG was confirmed by both autoantibodies and nerve-conduction tests, while its reactivation after TKIs rechallenge supports a more than coincidental association. The following review identified 12 cancer cases with TKI-related MG in six case reports and one case series. In most of them, the myasthenia diagnosis was challenging, since the clinical symptomatology of fatigable weakness was not corroborating with consistent laboratory and electrophysiological findings. In fact, anti-AchR titers were positive in five and anti-MuSK only in the abovementioned individual. The symptomatology corresponded to TKI discontinuation and standard treatment with pyridostigmine and prednisolone; intravenous immunoglobulin was added only in three, and two required mechanical ventilation. In an era where TKIs will be prescribed more frequently for various malignancies, even in combinations with immune-checkpoint inhibitors, this report synthesizes their risk for neuromuscular complications and increases the clinicians’ awareness in order to extend the on-treatment and overall survival of TKI-treated cancer patients.

scholarly journals Multitumor Case Series of Germline BRCA1, BRCA2 and CHEK2-Mutated Patients Responding Favorably on Immune Checkpoint Inhibitors

2021 ◽  
Vol 28 (5) ◽  
pp. 3227-3239
Author(s):  
Lisa Kinget ◽  
Oliver Bechter ◽  
Kevin Punie ◽  
Philip R. Debruyne ◽  
Hilde Brems ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Predictive Biomarkers ◽  
Solid Malignancies ◽  
Tumor Mutational Burden ◽  
Brca1 Brca2 ◽  
Tumor Types ◽  
Selection Of

In recent years, immune checkpoint inhibitors (ICPI) have become widely used for multiple solid malignancies. Reliable predictive biomarkers for selection of patients who would benefit most are lacking. Several tumor types with somatic or germline alterations in genes involved in the DNA damage response (DDR) pathway harbor a higher tumor mutational burden, possibly associated with an increased tumoral neoantigen load. These neoantigens are thought to lead to stronger immune activation and enhanced response to ICPIs. We present a series of seven patients with different malignancies with germline disease-associated variants in DDR genes (BRCA1, BRCA2, CHEK2) responding favorably to ICPIs.

Sign in / Sign up

Export Citation Format

Share Document