Complement-mediated thrombotic microangiopathy treated with anticomplement protein 5 therapy, a retrospective study.

BACKGROUND: Complement-mediated thrombotic microangiopathy (CM-TMA), also called atypical hemolytic uremic syndrome (aHUS), is a difficult-to-diagnose rare disease that carries severe morbidity and mortality. Anti-C5 monoclonal antibodies (aC5-mab) are standard treatments, but large studies and long-term data are scarce. Here, we report our single institution experience to augment the knowledge of CM-TMA treated with aC5-mab therapy. METHODS: We aimed to assess the short and long-term effects of aC5-mab in patients diagnosed with CM-TMA treated outside of a clinical trial. This was a retrospective study. We included all patients diagnosed with CM-TMA and treated with aC5-mab at our institution. There were no exclusion criteria. Endpoints included complete TMA response (CR) defined as normalization of hematological parameters and ≥25% improvement in serum creatinine (Cr) from baseline in patients with renal disease, relapse defined as losing the previously achieved CR, morbidity, adverse events, and survival. RESULTS: We found 28 patients with CM-TMA treated with aC5-mab. The median age was 50 years. Baseline laboratories: platelet counts 93 × 109 /L, hemoglobin 8.6 g/dL, lactate dehydrogenase 1326 U/L, serum Cr 4.7 mg/dL, and estimated glomerular filtration rate 19 mL/min. One individual was on renal replacement therapy (RRT) and 10 initiated RRT within 5 days of the first dose of aC5-mab. Genetic variants associated with CM-TMA included mutations in C3, CFB, CFH, CFHR1/3, CFI, and MCP. The mean duration of hospitalization was 24 days. The median time to initiation of aC5-mab was 10 days. Sixteen subjects received RRT. At the time of hospital discharge, 27 were alive, 14 remained on RRT, and 4 had a CR. At 6 months, 23 patients were alive, 18 continued aC5-mab, 8 remained on RRT, and 9 had a CR. At the last follow-up visit past 6 months, 20 were alive, 14 continued aC5-mab, 5 remained on RRT, 12 had a CR, and 1 was lost to follow-up. CONCLUSIONS: Our study provides real-world experience and insight into the long-term outcomes of CM-TMA treated with aC5-mab. Our findings validate that CM-TMA is an aggressive disease with significant morbidity and mortality, and confirm that aC5-mab is a relatively effective therapy for CM-TMA. Our study adds practical, real-world experience to the literature, but future research remains imperative.

Giroctocogene fitelparvovec gene therapy for severe hemophilia A: 104-week analysis of the phase 1/2 Alta study.

ABSTRACT: Patients with hemophilia A require exogenous factor VIII (FVIII) or nonfactor hemostatic agents to prevent spontaneous bleeding events. Adeno-associated virus (AAV) vector-based gene therapy is under clinical investigation to enable endogenous FVIII production. Giroctocogene fitelparvovec is a recombinant AAV serotype 6 vector containing the coding sequence for the B-domain-deleted human F8 gene. In the ongoing phase 1/2, dose-ranging Alta study, 4 sequential cohorts of male participants with severe hemophilia A received a single IV dose of giroctocogene fitelparvovec. The primary end points are safety and changes in circulating FVIII activity. Interim results up to 214 weeks after treatment for all participants are presented. Eleven participants were dosed. Increases in alanine and aspartate aminotransferases were the most common treatment-related adverse events (AEs), which resolved with corticosteroid administration. Two treatment-related serious AEs (hypotension and pyrexia) were reported in 1 participant within 6 hours of infusion and resolved within 24 hours after infusion. At the highest dose level (3 × 1013 vg/kg; n = 5), the mean circulating FVIII activity level at week 52 was 42.6% (range, 7.8%-122.3%), and at week 104 it was 25.4% (range, 0.9%-71.6%) based on a chromogenic assay. No liver masses, thrombotic events, or confirmed inhibitors were detected in any participant. These interim 104-week data suggest that giroctocogene fitelparvovec is generally well tolerated with appropriate clinical management and has the potential to provide clinically meaningful FVIII activity levels, as indicated by the low rate of bleeding events in the highest dose cohort. This trial was registered at www.clinicaltrials.gov as #NCT03061201.

Harnessing the Immune System: An Effective Way to Manage Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a heterogenous hematological disorder with malignant potential controlled by immunological characteristics of the tumor microenvironment. Rapid breakthrough in the molecular pathways has made immunological approaches the main anchor in the management of DLBCL, with or without chemotherapeutic agents. Rituximab was the first monoclonal antibody approved for the treatment of DLBCL. Following rituximab that transformed the therapeutic landscape, other novel immunological agents including chimeric antigen T-cell therapy have reshaped the management of relapsed/refractory DLBCL. However, resistance and refractory state remain a challenge in the management of DLBCL. For this literature review, we screened articles from Medline, Embase, Cochrane databases and the European/North American guidelines from March 2010 through October 2022 for DLBCL. Here we discuss immunological agents that will significantly affect future treatment of this aggressive type of lymphoma.

Insights into the Impact of Hesitancy on Cancer Care and COVID-19.

World Health Organization findings indicate that the COVID-19 pandemic adversely affected cancer diagnosis and management. The COVID-19 pandemic disrupted the optimal management of outpatient appointments, scheduled treatments, and hospitalizations for cancer patients because of hesitancy among patients and health-care providers. Travel restrictions and other factors likely affected medical, surgical, and radiation treatments during the COVID-19 pandemic. Cancer patients were more likely to be affected by severe illness and complications if they contracted COVID-19. A compromised immune system and comorbidities in cancer patients may have contributed to this increased risk. Hesitancy or reluctance to receive appropriate therapy or vaccination advice might have played a major role for cancer patients, resulting in health-care deficits. The purpose of this review is to evaluate the impact of COVID-19 on screening, entry into clinical trials, and hesitancy among patients and health-care professionals, limiting adjuvant and metastatic cancer treatment.

Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B.

BACKGROUND: Moderate-to-severe hemophilia B is treated with lifelong, continuous coagulation factor IX replacement to prevent bleeding. Gene therapy for hemophilia B aims to establish sustained factor IX activity, thereby protecting against bleeding without burdensome factor IX replacement. METHODS: In this open-label, phase 3 study, after a lead-in period (≥6 months) of factor IX prophylaxis, we administered one infusion of adeno-associated virus 5 (AAV5) vector expressing the Padua factor IX variant (etranacogene dezaparvovec; 2×1013 genome copies per kilogram of body weight) to 54 men with hemophilia B (factor IX activity ≤2% of the normal value) regardless of preexisting AAV5 neutralizing antibodies. The primary end point was the annualized bleeding rate, evaluated in a noninferiority analysis comparing the rate during months 7 through 18 after etranacogene dezaparvovec treatment with the rate during the lead-in period. Noninferiority of etranacogene dezaparvovec was defined as an upper limit of the two-sided 95% Wald confidence interval of the annualized bleeding rate ratio that was less than the noninferiority margin of 1.8. Superiority, additional efficacy measures, and safety were also assessed. RESULTS: The annualized bleeding rate decreased from 4.19 (95% confidence interval [CI], 3.22 to 5.45) during the lead-in period to 1.51 (95% CI, 0.81 to 2.82) during months 7 through 18 after treatment, for a rate ratio of 0.36 (95% Wald CI, 0.20 to 0.64; P<0.001), demonstrating noninferiority and superiority of etranacogene dezaparvovec as compared with factor IX prophylaxis. Factor IX activity had increased from baseline by a least-squares mean of 36.2 percentage points (95% CI, 31.4 to 41.0) at 6 months and 34.3 percentage points (95% CI, 29.5 to 39.1) at 18 months after treatment, and usage of factor IX concentrate decreased by a mean of 248,825 IU per year per participant in the post-treatment period (P<0.001 for all three comparisons). Benefits and safety were observed in participants with predose AAV5 neutralizing antibody titers of less than 700. No treatment-related serious adverse events occurred. CONCLUSIONS: Etranacogene dezaparvovec gene therapy was superior to prophylactic factor IX with respect to the annualized bleeding rate, and it had a favorable safety profile. (Funded by uniQure and CSL Behring; HOPE-B ClinicalTrials.gov number, NCT03569891.).

Primary immune thrombocytopenia: a 'diagnosis of exclusion'?

Current diagnosis of primary immune thrombocytopenia (ITP) is presumptive, centered on excluding other causes of thrombocytopenia. The diagnosis of ITP is challenging because of the wide range of potential inherited and acquired causes of thrombocytopenia. The treatment of ITP is empiric with steroids, high-dose immunoglobulin, immunosuppressants and thrombopoietin agonists with potential side effects. We searched Medline and Cochrane databases, reviewed the study data and analyzed the individual diagnostic tests for their evidence-based role in the diagnosis of ITP. We then analyzed the strength of the scientific evidence for each diagnostic test in the diagnosis of ITP and identified gaps in the diagnostic accuracy. The diagnostic challenges in ITP include: insufficient evidence for the individual test for diagnosis of ITP, no standardized protocol/guideline for diagnosis, hurdles in accessing the available resources and failure to correlate the clinical data while reviewing the blood smear. We did not identify a diagnostic test that clinicians can use to confirm the diagnosis of ITP. In the absence of a diagnostic test of proven value in ITP, the clinician is best served by a comprehensive history and physical examination, complete blood count and review of the peripheral blood smear in evaluating thrombocytopenia.

Assessment of Bleeding Risk in Hospitalized COVID-19 Patients: A Tertiary Hospital Experience during the Pandemic in a Predominant Minority Population-Bleeding Risk Factors in COVID-19 Patients.

Introduction: In the wake of the SARS-CoV-2 (COVID-19) pandemic, our world has faced multiple challenges. Infection with this virus has commonly been associated with thrombotic events. However, little is known about bleeding risk and anticoagulation therapy. This study aims to determine factors that are associated with increased risk of bleeding in COVID-19 patients. Methods: A retrospective cohort study was conducted using the records of COVID-19 patients admitted during the COVID-19 pandemic from March 2020 through May 2020. Using patient charts, investigators manually collected data regarding patient characteristics and bleeding. Patients were included in the analysis if they had a confirmed COVID-19 PCR test, were older than 18 years of age and were admitted to the hospital. Patients who were pregnant or had incomplete charts were excluded from the study. ANOVA and logistic regression were used to determine the statistical significance of the data using SPSS version 27. Results: A total of 651 patients were included in the analysis out of 685 patients located in the database of COVID-19 infected patients during that time frame. The general characteristics of the patients were as follows: 54.2% were males; females 45.8% ages ranged from 28 to 83 years old (median age = 66 years old). There were 31 patients (4.9%) who required more than 1 unit of packed red blood cell (PRBC). A total of 16 (2.85%) patients had a documented gastrointestinal bleed (GIB), of which 8 received a total of 29 units of PRBC transfusions. The HAS-BLED score (without alcohol/drug due to inadequate charting) is calculated for patients who had a documented GI bleed and who received more than one unit of PRBC. It was noted that the higher the HAS-BLED score the greater the likelihood of having a GI bleed (p < 0.001). The HAS-BLED score (not including alcohol/drug) was also predictive for patients who received more than one unit of PRBC during their hospital stay (p < 0.001). Discussion: Using the HAS-BLED score without alcohol/drugs, patients with COVID-19 can be stratified in regard to their risk of GI bleeding and their risk of transfusion while in the hospital. When administering anticoagulation therapy, cautious monitoring should be carried out. Decisions regarding anticoagulant therapy should be based on individual patient characteristics.

Post Approval Experience with Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura at a Single Institution.

Caplacizumab prevents platelet adhesion and has been approved for acquired thrombotic thrombocytopenic purpura (aTTP). This study was retrospective, including all patients diagnosed with aTTP and treated with caplacizumab since commercial availability in 2019 until 28 February 2021 at a single academic hospital with no exclusion criteria. Results used definitions for outcomes in aTTP from the International Working Group Consensus. Ten patients with aTTP received caplacizumab. The median age was 52 years. Six (60%) patients had refractory aTTP while 4 (40%) had newly diagnosed aTTP. The median laboratory values prior to therapy demonstrated: platelet count (PC) 29/uL, LDH 518 U/L (182-1850), ADAMTS13 activity 3% and ADAMTS13 inhibitor 1.4 BU. Everyone received glucocorticoids, rituximab, therapeutic plasma exchange (TPE) and caplacizumab. The median number of TPE was 12 days. Caplacizumab was started at a median of 5 days after the first TPE and the median treatment duration was 31 days. Normalization of PC, LDH and ADAMTS13 activity in days were 5, 3.5, and 32.5, respectively. Six (60%) patients achieved complete response, 3 (30%) had refractory disease and 1 (10%) had relapsed aTTP. No subject suffered abnormal bleeding, or thrombotic event. There were no deaths. Caplacizumab with TPE, glucocorticoids and rituximab was a safe and effective therapy for aTTP.

Efficacy and safety of direct oral anticoagulants for secondary prevention of cancer associated thrombosis: a meta-analysis of randomized controlled trials.

Direct oral anticoagulants (DOACs) may be good alternatives to low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) for treatment of cancer associated thrombosis (CAT). We conducted a meta-analysis of ten randomized clinical trials to evaluate the efficacy and safety of DOACs in patients with CAT. All had study populations composed in entirety or in part of patients with CAT. The primary outcome (efficacy) was recurrent VTE and the secondary outcomes (safety outcomes) included major bleeding, clinically relevant non-major bleeding (CRNMB), and all bleeding (major bleeding + CRNMB). Participants treated with DOACs had lower risk of recurrent VTE, overall (RR 0.63; 95% CI 0.51-0.79; p < 0.0001), compared to LMWH (RR 0.57; 95% CI 0.40-0.83; p = 0.003), but not compared to VKA (RR 0.69; 95% CI 0.44-1.06; p = 0.09). Compared to LMWH, DOACs showed no difference in major bleeding risk (RR 1.31; 95% CI 0.78-2.18; p = 0.31), though had higher risk of CRNMB (RR 1.60; 95% CI 1.13-2.26; p = 0.008) and all bleeding (RR 1.49; 95% CI 1.10-2.01; p = 0.010). These results indicate that DOACs are more effective than LMWH for prevention of recurrent VTE with CAT though carry an increased risk for non-major bleeding compared to standard of care, LMWH.

A phase I/II study of docetaxel in combination with pegylated liposomal doxorubicin in metastatic castration-resistant prostate cancer.

Taxanes and anthracyclines have been among the best-studied chemotherapy classes in castration-resistant prostate cancer (CRPC). Docetaxel (D) 75 mg/m2 every 3 weeks has been the standard first line chemotherapy for CRPC. Encapsulation of doxorubicin in polyethylene glycol-coated liposomes (PLD) was developed to enhance the safety and efficacy of conventional doxorubicin. We hypothesize that the combination of weekly low dose-D and PLD would result in a high response rate and low toxicity. Eligibility criteria included metastatic progressive CRPC, no prior D or PLD and good organ function. After a short phase I with no dose-limiting toxicity, D 30 mg/m2 was administered on days 1, 8 and 15; and PLD 30 mg/m2 on day 1 only, every 28 days. Thirty-seven patients were enrolled. The PSA response rate was 53%. Twenty-two subjects had measurable disease; one (5%) achieved complete response, five (23%) partial response, and twelve (54%) stable disease. Twenty-seven patients (73%) manifested pain relief. The median time to progression was 3.7 months for all patients and 7.9 months for responders. Median overall survival was 16.3 months. Grade 4 neutropenia without infection and anemia occurred in 1 patient each. Grade 3 treatment-related toxicities included: 15% fatigue; 9% neutropenia, anemia and nausea; 6% dehydration and hand-foot syndrome; and 3% infection, febrile neutropenia, thrombosis, stomatitis, headache, vomiting, weight loss and weakness. In this non-comparative study D-PLD demonstrated a higher activity than previously reported with single agent D with favorable side effect profile. A phase 3 study would be needed to evaluate the true benefit of this combination.ClinicalTrials.gov Identifier: NCT00456989.

Chronic pain in patients with hemophilia: is it preventable?

: Current management of chronic pain in patients with hemophilia (PWH) focuses on pain relief with analgesics and symptom control. The clinical practice of managing chronic pain in PWH varies considerably across hemophilia treatment centers. Here, we aim to study the appropriate intervention of hemophilic arthropathy for prevention and treatment of chronic pain in PWH. Medline, Embase, Cochrane databases were searched for randomized controlled trials, and the European Hemophilia Therapy Standardization Board, The World Federation of Hemophilia, Nordic Hemophilia Guidelines, American Society of the International Pain Physicians and the Medical and Scientific Advisory Council guidelines were studied through November 2019 for chronic pain in PWH for a narrative review. We found no standardized approach for the prevention and management of chronic pain in PWH. Evidence suggests that prophylactic factor concentrate therapy, programmed exercise and educational intervention may help PWH manage their chronic pain.

Hematological Malignancies and Arterial Thromboembolism.

Established guidelines exist for prevention and treatment of venous thromboembolism in hematological malignancies, but none for arterial thromboembolism. However, arterial and venous thromboembolism share the same provoking features-including altered procoagulant factors and defective fibrinolytic system. The morbidity for arterial thromboembolism is increasing in hematological malignancies, with the advent of immunomodulatory and targeted therapy. However, survival rate for hematological malignancy is improving. Consequently, as patients with hematological malignancies live longer, comorbidities including diabetes, hypertension and dyslipidemia, may accentuate arterial thrombosis. Thus far, the scientific literature on prophylaxis and treatment for arterial thromboembolism in hematological malignancies is limited. This review highlights the pathogenesis, incidence and clinical features of arterial thromboembolism in hematological malignancies.

Validation of the Khorana score in acute myeloid leukemia patients: a single-institution experience.

BACKGROUND: Although patients with acute myeloid leukemia (AML) were shown to have an increased risk of thrombosis, no thrombosis risk assessment scoring system has been developed for AML patients. The Khorana Risk Score (KRS), which has been widely used for thrombosis risk assessment in the clinical setting, was developed on the basis of solid tumor data and has not been validated among AML patients. This study aims to validate the use of the KRS as a thrombosis risk-scoring system among patients with AML. METHODS: Using data from H. Lee Moffitt Cancer Center and Research Institution's Total Cancer Care Research Study, we retrospectively identified patients who were histologically confirmed with AML from 2000 to 2018. Clinical and laboratory variables at the time of AML diagnosis were characterized and analyzed. The thrombotic event rate was estimated with the Kaplan-Meier method and compared using the log-rank test. RESULTS: A total of 867 AML patients were included in the analysis. The median age at AML diagnosis was 75 years (range, 51-96), and the majority were male (65%, n = 565). A total of 22% (n = 191), 51% (n = 445), 24% (n = 207), and 3% (n = 24) of patients had a KRS of 0, 1, 2, and 3, respectively. A total of 42 thrombotic events (3% [n = 6/191] with a KRS of 1; 5% [n = 23/445] with a KRS of 2; 6.3% [n = 13/207] with a KRS of 3) were observed, with a median follow-up of 3 months (range, 0.1-307). There was no statistical difference in the risk of thrombosis between these groups (P = .1949). CONCLUSIONS: Although there was an increased risk of thrombosis associated with a higher KRS among AML patients with a KRS of 1 to 3, the difference was not statistically significant. Furthermore, only a few patients were found to have a KRS > 3, and this was largely due to pancytopenia, which is commonly associated with AML. These results indicate the need for a better thrombotic risk-scoring system for AML patients.

Evolving paradigm in thrombophilia screening.

: The role of genetic thrombophilia screening for identifying a hypercoagulable state in the management of venous thromboembolism. We searched MEDLINE and EMBASE from 1995 to 2017, the websites of the professional bodies including American Society of Hematology, British Society of Hematology, International Society of Thrombosis and Hemostasis, College of American Pathologists, American College of Medical Genetics, and American Society of obstetrics and gynecology for their clinical practice guidelines. We used search strategy terms - venous thromboembolism, inherited, thrombophilia, and hypercoagulable state. Thrombophilia screening does not alter management in pregnancy, infertility, recurrent miscarriages, in primary occlusive arterial syndromes, and for primary prevention in relatives of venous thromboembolism patients considering hormonal manipulation including oral contraceptives. Routine thrombophilia screening for identifying a hypercoagulable state is not indicated in venous thromboembolism, as it is only useful in a select group of patients. There is no difference in the treatment of venous thromboembolism in patients with or without an inherited hypercoagulable state.

Phase 2 Study of Cyclophosphamide, Etoposide, and Estramustine in Patients With Castration-Resistant Prostate Cancer.

BACKGROUND: There are no effective chemotherapies for patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease has failed to respond to taxanes or patients who do not wish to receive intravenous drugs. We hypothesized that low doses of multiple medications with prolonged exposure would result in a high response rate and low toxicity. PATIENTS AND METHODS: Patients with mCRPC were eligible for this phase 2 trial. The primary endpoint was a prostate-specific antigen decrease of more than 50%. CEE consisted of cyclophosphamide (50 mg/m2), etoposide (50 mg/m2), and estramustine 280 mg provided orally once a day for 14-day cycles every 28 days. RESULTS: Fifty-two patients were enrolled and included in all evaluations. The prostate-specific antigen response rate was 46% in all patients, 53% in chemotherapy-naive subjects, and 31% after docetaxel chemotherapy. Thirty subjects had measurable lesions, 1 (3%) had complete response, 2 (7%) partial response, and 22 (73%) stable disease, for a clinical benefit of 83%. Sixty percent experienced an improvement in their performance status, and 65% reported improvement in their pain. The median overall survival was 18.6 months in all patients, 20.4 months in chemotherapy-naive patients and 11.3 months in patients whose disease progressed while receiving docetaxel therapy. Grade 3/4 treatment-related toxicities included 20% neutropenia, 10% thrombocytopenia, 10% deep-vein thrombosis, 8% anemia, 8% fatigue, 4% death, and 2% anorexia and stomatitis. CONCLUSION: CEE was an all-oral, easy-to-administer, and effective triple-drug therapy for patients with mCRPC.

Case Report: CEA Elevation Can Be a Marker of Increased Inflammation During Treatment with Oxaliplatin.

Oxaliplatin is a platinum-based chemotherapy that is an integral part of several regimens for colorectal cancer. We present the case of a patient, a 58-year-old male, who had initially presented aged 56 years with rectal bleeding for several months. His serum carcinoembryonic antigen (CEA) level at the time of diagnosis was 4.6 ng/ml. His CEA level increased significantly during oxaliplatin-based chemotherapy and declined to a near normal level after completion of therapy. There was no evidence of disease during this time and he remains disease-free. Oxaliplatin has been shown to cause an inflammatory response which appears to be one of the mechanisms of toxicity and high CEA levels have been correlated with increased inflammation. We postulate that this patient's rising CEA level was secondary to an inflammatory response to oxaliplatin-based therapy, which is further supported by the subsequent decrease after completion of chemotherapy. To our knowledge, this is the first published case of oxaliplatin-induced rising CEA level.

Nivolumab as salvage treatment in a patient with HIV-related relapsed/refractory Hodgkin lymphoma and liver failure with encephalopathy.

BACKGROUND: We report the first case to our knowledge of a patient with relapsed/refractory classical hodgkin lymphoma and liver failure with encephalopathy along with human immunodeficiency virus/acquired immunodeficiency syndrome infection, successfully treated with nivolumab without major side effects and encouraging prolonged disease control. CASE PRESENTATION: In December 2015, at the time of the patient's progression from his Hodgkin lymphoma after fourth line treatment, he developed persistent fevers, abdominal distension, jaundice and worsening of his liver function tests. Magnetic resonance imaging of abdomen/pelvis demonstrated hepatomegaly with innumerable new liver lesions, splenomegaly with multiple splenic nodules and several new mediastinal, intraperitoneal and retroperitoneal lymphadenopathy. In accordance with the patient's wishes before admission, and after agreement with the family, nivolumab (3 mg/kg every 2 weeks) was given. Of note, antiretroviral therapy was on hold due to liver function tests, his viral load was undectable and cluster of differentiation 4 counts were 103/uL at the time of nivolumab administration. One week after the first dose of nivolumab both his hepatic encephalopathy and constitutional symptoms started to improve, and after 2 doses, (January 2016) his LFTs were almost back to normal. After 5 months of nivolumab treatment (10 doses), restaging (computerized tomography scans of neck, chest, abdomen, pelvis) done on May 2016 showed resolution of hepatosplenomegaly with two residual small hepatic lesions, heterogeneous spleen with no splenic lesions, and stable non-enlarged retroperitoneal lymph nodes without intraabdominal lymphadenopathy; consistent with partial response. CONCLUSIONS: We report a case of a patient with human immunodeficiency virus/acquired immunodeficiency syndrome -related relapsed/refractory classical Hodgkin lymphoma and acute liver failure with encephalopathy successfully treated with nivolumab after failing all standard therapeutic options. Unlike classic cytotoxic chemotherapy, which relies on preserved organ function to ameliorate potential severe side effects (i.e. myelosuppression), elimination of monoclonal antibodies is fairly independent of baseline renal and hepatic function since they are usually metabolized by circulating phagocytes and/or by their target antigen-expressing cell.