Incidence Of Tumor Lysis Syndrome Research Articles

Effects and outcomes of tumor lysis syndrome in patients admitted with Hodgkin and non-Hodgkin lymphoma: A National Inpatient Sample study (2019-2020).

e19032 Background: Tumor Lysis Syndrome (TLS) is a life-threatening oncologic emergency. The newer advancement in therapeutic approaches in oncology has widened the range of malignancies associated with TLS. A lot of literature on the incidence of TLS in various solid malignancies exists. However, the effects of TLS on hematological malignancies, especially Hodgkin’s Lymphoma (HL) and Non-Hodgkin’s Lymphoma (NHL) have rarely been analyzed. Our study aims to identify the impact of TLS in patients hospitalized with HL and NHL and draw a comparison between HL and NHL. Methods: We analyzed the National Inpatient Sample database from 2019 - 2020 to identify patients > 18 years old with a primary diagnosis of HL and NHL. We compared the TLS prevalence and all-cause in-hospital mortality, length of hospital stay (LOS), and total costs in patients admitted with HL and compared it with NHL. Categorical variables were compared using the chi-square test, and the t-test compared continuous variables. Multivariable regression analyses were performed adjusting for demographics, hospital-level characteristics, and relevant comorbidities. Results: Among 24,550 Hodgkin’s Lymphoma (HL) hospitalizations and 108,060 Non-Hodgkin’s Lymphoma (NHL) hospitalizations, TLS was diagnosed in 0.69% of HL patients and 0.89% of NHL patients. In-hospital mortality was significantly higher in both HL (44.1%) and NHL (28.3%) patients with TLS compared to those without TLS (HL: 4.5%, NHL: 5.1%). Multivariate regression analysis revealed that TLS presence increased the chance of mortality among both HL (OR 17.9) and NHL (OR 7.3) patients. TLS also significantly impacted secondary outcomes including Acute Kidney Injury (AKI) and Hyperkalemia in both HL and NHL patients. No statistically significant differences were found in the odds of cardiac arrhythmias between HL and NHL patients with TLS (Table). TLS was associated with longer Length of Stay and higher total hospital costs in both HL and NHL patients compared to those without TLS. Conclusions: TLS is significantly associated with increased mortality in patients with HL and NHL, more in HL compared to NHL. In patients with HL, and NHL, TLS is an independent risk factor for in-patient mortality, the longer LOS, and the total cost, thereby incurring an increased burden on healthcare resources. Our study aims to highlight the need for greater vigilance in this vulnerable group when TLS occurs. [Table: see text]

Tumor lysis syndrome in induction therapy for acute myeloid leukemia before the rasburicase era.

Guidelines recommend rasburicase for high-risk patients to prevent tumor lysis syndrome (TLS). However, little information is available on the incidence and outcome of TLS in AML patients. We analyzed 145 patients with AML who underwent induction therapy before the approval of rasburicase to evaluate the incidence of TLS and the necessity of rasburicase as prophylaxis. Three patients had already developed clinical TLS (CTLS) at diagnosis of AML, and another three developed CTLS after the initiation of chemotherapy. In patients without TLS at diagnosis of AML, the risk for developing TLS was classified as high in 44 patients, intermediate in 41 and low in 57, according to the current guidelines. Allopurinol alone was administered to prevent hyperuricemia in all patients. All three patients who developed CTLS after diagnosis of AML were at high risk of TLS, and had elevated serum creatinine levels and a WBC count greater than 200,000 per microliter at diagnosis of AML. Allopurinol may be insufficient to prevent TLS in high-risk patients with renal dysfunction at diagnosis of AML, especially those with a high tumor burden and a WBC count of 200,000 or more, which indicates that prophylactic administration of rasburicase should be considered.

A Study to Evaluate the Effectiveness and Safety of Prephase Steroid Treatment before Remission Induction Chemotherapy in Patients with Pediatric Acute Lymphoblastic Leukemia Using Common Data Model-Based Real-World Data: A Retrospective Observational Study.

Rapid reduction of leukemic cells in the bone marrow during remission induction chemotherapy (RIC) can lead to significant complications such as tumor lysis syndrome (TLS). We investigated whether prephase steroid treatment before RIC could decrease TLS incidence and improve overall survival in pediatric patients with acute lymphoblastic leukemia (ALL). Data were extracted from the Common Data Model databases in two tertiary-care hospitals in Seoul, South Korea. Patients were classified into the treated or untreated group if they had received RIC with prephase steroid treatment ≥7 days before RIC in 2012-2021 or not, respectively. Stabilized Inverse Probability of Treatment Weighting (sIPTW) was applied to ensure compatibility between the treated and untreated groups. The incidence of TLS within 14 days of starting RIC, overall survival (OS), and the incidence of adverse events of special interest were the primary endpoints. Multiple sensitivity analyses were performed. Baseline characteristics were effectively balanced between the treated (n=308.4) and untreated (n=246.6) groups after sIPTW. Prephase steroid treatment was associated with a significant 88% reduction in the risk of TLS (OR 0.12, 95% CI: 0.03-0.41). OS was numerically greater in the treated group than in the untreated group although the difference was not statistically significant (HR 0.64, 95% CI 0.25-1.64). The treated group experienced significantly elevated risks for hyperbilirubinemia and hyperglycemia. The reduction in TLS risk by prephase steroid treatment was maintained in all of the sensitivity analyses. Prephase steroid treatment for ≥7 days before RIC in pediatric patients with ALL reduces the risk of TLS, while careful monitoring for toxicities is necessary. If adequately analyzed, real-world data can provide crucial effectiveness and safety information for proper management of pediatric patients with ALL, for whom prospective randomized studies may be difficult to perform for ethical and practical reasons.

Low incidence of tumor lysis syndrome in elderly patients with chronic lymphocytic leukemia treated with venetoclax under real-world conditions: results from the prospective observational VeRVe study.

Venetoclax is active in both frontline and relapsed/refractory settings for the treatment of chronic lymphocytic leukemia (CLL). Although the prevalence and severity of tumor lysis syndrome (TLS) are well characterized in clinical trials, laboratory and clinical TLS remain relatively unexplored in real-world clinical practice.In this prospective, real-world observational study, we aimed to determine the incidence and outcomes of TLS in patients with CLL receiving venetoclax outside a clinical trial. The study (VeRVe) was conducted in centers in Austria, Germany, and Switzerland.Two hundred and thirty-nine patients were treated according to local label with at least one dose of venetoclax. Patient demographics, baseline characteristics, and blood chemistry at baseline were documented, and descriptive statistical analyses were conducted.Seventy eight patients (33%) were treated with venetoclax monotherapy, 101 (42%) with venetoclax in combination with rituximab and 60 (25%) with venetoclax in combination with obinutuzumab. In all cases, the TLS risk mitigation strategy adhered to the ramp-up protocol. Median age was 73 years and 66% of patients were male. The majority of patients (75%) had relapsed/refractory CLL, 63/192 (32.8%) patients tested had a del(17p) and 93/134 (69.4%) patients tested had unmutated immunoglobulin heavy chain variable region gene (IGHV). Clinical TLS occurred in 5 patients (2.1%) and laboratory TLS occurred in 15 patients (6.3%). Ten patients received specific treatment, of which 6 were hospitalized. There were no deaths due to a TLS event and venetoclax was well-tolerated. Of the 5 clinical TLS events reported, none were fatal or resulted in renal failure (NCT03342144, registered on Nov 10, 2017).

Management and use of healthcare resources in patients with chronic lymphocytic leukemia initiating venetoclax in routine clinical practice

Venetoclax is a first-in-class B-cell lymphoma-2 (BCL-2) inhibitor approved as continuous monotherapy and in combination with rituximab as fixed-treatment duration for relapsed and refractory chronic lymphocytic leukemia (R/R CLL). DEVOTE was a 24-week, multicenter observational study (NCT03310190) evaluating the safety, healthcare resource utilization (HCRU) and health-related quality of life (HRQoL) of patients initiating venetoclax for R/R CLL in Canada. Overall, 89 patients received 1 dose of venetoclax; 80% had prior exposure (42% resistant) to ibrutinib. Biochemical tumor lysis syndrome (TLS) occurred in five patients. We observed differences in hospitalization across Canadian provinces including in patients at low risk for TLS with no clear impact on TLS incidence. Additionally, a rapid and sustained improvement in several domains of HRQoL was observed during venetoclax initiation. Early adoption of venetoclax was mainly for R/R CLL patients with few treatment options; nonetheless, acceptable toxicity and a positive impact on HRQoL were observed.

R-CHOP Versus CHOP-R: Influence of Rituximab Timing on Real-World Outcomes in Patients with Diffuse Large B Cell Lymphoma

Diffuse large B cell lymphoma (DLBCL) is the most common aggressive lymphoma and is conventionally treated with the chemotherapy regimen R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). The major clinical trials of R-CHOP administered rituximab on the same day as CHOP chemotherapy (R-CHOP). However, in real-world community oncology settings physicians often delay rituximab treatment until after chemotherapy is complete (CHOP-R). This is due to both concerns about drug reimbursement rates in the hospital versus outpatient setting and toxicity considerations. In particular, there is anecdotal evidence and limited retrospective data (Hannawa et al, J Oncol Pharm Pract 2011) that infusion reactions with rituximab may be lessened if rituximab administration is delayed until after CHOP chemotherapy. The current study aims to compare the incidence of infusion reactions, tumor lysis syndrome (TLS), and treatment efficacy in a retrospective cohort of DLBCL patients who received rituximab administration before chemotherapy (R-CHOP) versus those who received it after chemotherapy (CHOP-R). In the current study, we reviewed 178 adult patients with DLBCL who received R-CHOP or CHOP-R between 9/1/2011 and 9/1/2021 at our institution. Treatment groups were defined based on the treatment received during the first cycle of chemotherapy. Patients were identified and data was extracted from electronic health records using Epic's SlicerDicer tool and integrated with data from manual chart review. A two-tailed Fisher's exact test with a significance level of 0.05 was used to analyze 2x2 tables describing the incidence of infusion reactions and tumor lysis syndrome. The study cohort consisted of 178 patients including 139 patients (78%) in R-CHOP group and 39 patients (22%) in CHOP-R group. The median age at diagnosis was 65 years (range 22-92) in the R-CHOP group and 72 years (range 29-86) in the CHOP-R group. The R-CHOP group was approximately evenly split between female (51%) and male (49%), however the CHOP-R group was mostly male (69%). Double hit status was known in 96 patients (3 patients positive and 93 patients negative) in the R-CHOP group and 34 patients (4 patients positive and 30 patients negative) in the CHOP-R group. More patients in CHOP-R group had stage III/IV lymphoma (82%) as compared to the R-CHOP group (61%). HIV associated lymphoma at the time of diagnosis was reported in 3 patients in R-CHOP group vs 1 patient in CHOP-R. Median rituximab -containing cycles received in R-CHOP group were 6 (range 1-6) and CHOP-R group were 5 (range 1-6). We examined the incidence of acute infusion reactions within 24 hours of rituximab administration during the first cycle of chemotherapy. Symptoms/signs of infusion reactions that we examined included fever, chills, rigors, hypotension, hypertension, hypoxia and tachycardia. Patients who did not have adequate data available were excluded from analysis. A total of 29% of patients in the R-CHOP group experienced any infusion reaction as compared to 21% of patients in the CHOP-R group. Data on the incidence of TLS, defined as per the Cairo-Bishop criteria, was collected. Patients who had limited laboratory data available were excluded from analysis. A total of 12% of patients in the R-CHOP group experienced TLS as compared to 17% in the CHOP-R group (p=0.52). Most TLS was present prior to the initiation of treatment. In conclusion, our study found no statistically significant difference in the incidence of acute infusion reactions or tumor lysis syndrome when rituximab administration is delayed. Data on efficacy and survival outcomes will be presented.

A Study to Evaluate the Effectiveness and Safety of Prephase Steroid Treatment before Remission Induction Chemotherapy in Patients with Pediatric Acute Lymphoblastic Leukemia Using Common Data Model-Based Real World Data

Introduction: Remission induction chemotherapy (RIC) is a primary treatment strategy for pediatric acute lymphoblastic leukemia (ALL), aiming to rapidly reduce leukemic cells in the bone marrow. However, this swift reduction can lead to significant complications such as tumor lysis syndrome (TLS). Pretreatment with steroids such as prednisolone or dexamethasone a week before initiating multi-agent RIC can potentially prevent TLS, but the effectiveness and utility of this approach remains unclear. We investigated whether steroid pretreatment before RIC can decrease TLS incidence and improve overall survival. Methods: We utilized clinical databases from two university-affiliated tertiary-care hospitals in Seoul, South Korea, constructed according to the OMOP Common Data Model (CDM) specifications. Eligible patients were children with ALL aged <18 who received RIC consisting of vincristine, prednisolone, L-asparaginase with or without daunorubicin between 2012 and 2021. Patients who received steroid pretreatment ≥7 days before RIC constituted the treated group, whereas those who didn't receive any steroid pretreatment or received it <7 days before were the untreated group. We used propensity score (PS) matching to make baseline characteristics comparable between the groups, based on logistic regression model that incorporated the following covariates: age at ALL diagnosis, sex, presence of Down syndrome, risk group, and baseline laboratory measurements including white blood cell count, hemoglobin, platelet count, absolute neutrophil count, uric acid, phosphorus, potassium, calcium, blood urea nitrogen, creatinine, and lactate dehydrogenase. The primary and secondary outcomes were the incidence of TLS within 14 days of starting RIC and overall survival (OS), respectively. Sensitivity analyses were performed to evaluate if unmeasured confounders resulted in any difference in the main results. Likewise, a rule-out approach and a negative control method was applied to adjust for confounders like immunophenotype and genetic alterations and for other residual confounding, respectively. Results: The study included 574 pediatric patients with ALL, with 275 in the treated group and 299 in the untreated group. After PS matching, each group included 142 patients with all baseline characteristics being comparable. Among the untreated patients, TLS was observed 32 out of 299 (10.7%), whereas in the treated group, 6 out of 275 (2.2%) developed TLS. The significant association between the treatment and reduced TLS risk persisted after adjusting for potential confounders (adjusted OR = 0.08, 95% CI: 0.01-0.31, p = 0.01). OS was numerically greater in the treated group that in the untreated group although it failed to reach statistical significance (HR 0.78, 95% CI 0.35-1.71, p=0.53). Sensitivity analyses including a rule-out approach and a negative control method indicated no substantial impact from unmeasured confounders such as immunophenotype, genetic alterations, or other residual factors. Conclusions: Steroid pretreatment ≥7 days before RIC significantly reduced the risk of TLS in pediatric patients with ALL although no significant reduction in OS was seen in the treated group than in the untreated group, partly because median OS was not reached. Because prospective randomized studies are ethically challenging to assess the efficacy and safety of steroid pretreatment before RIC, our results can provide its critical real-world evidence.

Comparing Cairo Bishop and Howard Criteria for Identifying Clinically Meaningful Tumor Lysis Syndrome Among Acute Myeloid Leukemia Patients Treated with Venetoclax and Hypomethylating Agents: A Single Center Experience

Introduction Venetoclax (ven) in combination with hypomethylating agents (HMA) is the standard of care for the treatment of acute myeloid leukemia (AML) in patients (pts) who are ineligible for intensive chemotherapy. The most serious complication of ven is tumor lysis syndrome (TLS). The phase 1b trial of ven and HMA in AML pts included strict prophylactic measures to prevent TLS. Reported rates of TLS in real world cohorts vary widely and prophylactic measures are not standardized. Methods Here we describe TLS prophylaxis (ppx) and incidence in a cohort of 100 consecutive pts age ≥18 years at the University of Pennsylvania who received inpatient or outpatient ven and HMA for up front treatment of AML between 1/2017-8/2022. TLS ppx was at the discretion of the treating team. TLS was retrospectively defined by Cairo Bishop and Howard Criteria (table 1). Howard TLS (H-TLS) criteria differs from Cairo Bishop TLS (CB-TLS) in that it requires two lab abnormalities be present in the same 24-hour period, uses calcium corrected for albumin and does not include ≥25% changes from baseline lab values. Results 92 pts had a white blood cell count (WBC) <25,000 cells/μL on the first day of treatment (table 1). 34 pts developed laboratory (lab) CB-TLS; 8 of these pts met criteria for clinical CB-TLS due to acute kidney injury (AKI). 13 pts developed CB-TLS prior to starting ven. While the original phase 1b trial mandated frequent lab monitoring as well as starting allopurinol ≥72 hours prior to ven and suggested a target of 2L of intravenous (IV) fluid per day starting the night prior to ven, TLS ppx was variable in our pts. 56 pts received allopurinol ≥72 hours prior to starting ven, 21 received ≥2L of IV fluid per day starting at least the day prior to ven, and 56 had TLS labs measured every 8-12 hours during the first 3 days following ven initiation. CB-TLS was associated with a higher ECOG score and baseline lactate dehydrogenase as well as FLT3 and NPM1 mutations. The CB-TLS group had a higher mean WBC count but there was no difference in the proportion of pts with WBC counts ≥25,000 cells/μL. There was a trend towards increased CB-TLS in pts with WBC counts ≥15,000 cells/μL; this reached statistical significance when comparing the percent of pts with non-spontaneous CB-TLS with WBC count ≥15,000 cells/μL to the rest of the cohort (33% vs 13%, p=0.034). To characterize TLS severity, we categorized the pts with CB-TLS into three groups: insignificant TLS, significant TLS, and those whose lab abnormalities were explained by a different pathology. We defined significant TLS as pts who required hospitalization (if started treatment outpatient) or ICU transfer, received rasburicase, developed AKI, or had treatment held due to TLS. 17 pts had insignificant TLS, 14 had significant TLS, and 3 were ultimately felt not to have TLS (table 2). We also compared pts who developed CB-TLS with those who met criteria for H-TLS. Of the 34 pts who met lab CB-TLS criteria, only 6 also met Howard criteria. All 6 of these pts had significant TLS. Of the 8 pts with significant TLS who only met Cairo Bishop criteria, 6 developed spontaneous TLS >3 days prior to starting treatment with ven that would have met H-TLS criteria at onset. Their lab abnormalities were not as severe by ≤3 days prior to ven start when the formal time frame for defining TLS begins. Discussion Other studies have shown lab TLS rates of 0-40% in AML pts receiving ven with HMA, with the majority reporting rates <10%. Our data show a higher rate of lab CB-TLS than other published cohorts. However, our data also show that most pts do not develop significant TLS despite less aggressive ppx than was used in the original ven trial and suggest that less aggressive ppx is appropriate for most pts. There was a high rate of spontaneous TLS in our cohort. Debate exists over the most appropriate WBC threshold for ven initiation; our data suggest an association of WBC count <15,000 cells/μL with lower TLS risk. Of the pts who developed significant TLS, a majority had spontaneous TLS; only 5 pts had significant TLS occur after starting ven. We also found that the Howard criteria for TLS better identify pts who will have adverse outcomes from TLS and may be a more clinically meaningful set of criteria to use in future studies.

Tumor lysis syndrome in patients with acute myeloid leukemia treated with venetoclax and hypomethylating agents with or without dose ramp-up

Venetoclax with hypomethylating agents (HMAs) is an important treatment for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. However, there is limited data on the safety of venetoclax without a dose ramp-up in patients with AML. A retrospective cohort analysis of patients with AML treated with HMA/venetoclax (HMA/Ven) with or without a dose ramp-up, or HMA alone from 6/30/2014–8/22/2022 was conducted. The primary endpoint was the incidence of laboratory and/or clinical tumor lysis syndrome (TLS) by day 10. Of 225 patients, 111 patients received HMA alone or HMA/Ven with a dose ramp-up and 114 received HMA/Ven with no dose ramp-up. The incidence of TLS was similar between the control and no dose ramp-up groups, with rates of 5.4% and 5.3% respectively (p = 0.962). TLS incidence was comparable in patients with and without a dose ramp-up, suggesting that a dose ramp-up may not be mandatory in patients with AML.

Tumor lysis syndrome in solid tumors: A retrospective cohort study of the National Inpatient Sample from 2016 to 2019.

6594 Background: Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency. Patients with a rapidly proliferating tumor or high tumor burden after cytotoxic chemotherapy, predominantly in hematologic malignancies, are at increased risk of TLS. The advancement in therapeutic strategies of oncology in the past few decades has expanded the spectrum of malignancies associated with TLS. A dearth of literature on the incidence of TLS in various solid malignancies exists. Using the National Inpatient Sample (NIS) data, this study aims to highlight the solid malignancies at risk of TLS, highlight the demographic factors, and draw a comparison with that in hematological malignancies. Methods: The NIS 2016-2019 dataset was analyzed utilizing univariate and multivariate logistic regression analysis for the predictors of TLS (P <0.05). StataCorp. 2021. Release 17. College Station, TX: StataCorp LLC, BE version with Stata’s svy command, and appropriate weights, were used to perform the analysis. The overall fit was analyzed using Receiver Operative Curves (ROC), and sensitivity analysis was analyzed using the e-value package. Results: From 2016-2019, a total of 51,385 (48,917-53,853) hospitalizations had an incidence of TLS. We included 16,249 cases of TLS in patients treated for the ten most common malignancies in the US. We found that older age, male sex, and black race were associated with higher odds of TLS. It was reported highest in large hospitals and urban non-teaching hospitals. The regional distribution of the TLS suggests the highest odds in the Western region. The odds of getting TLS were highest among Leukemias and Lymphomas, respectively. Among solid tumors, the odds of getting TLS were highest in uterine cancer patients, followed by lung, breast, pancreatic, and liver cancer among the top five. (Table). Conclusions: In this study, we conclude that solid tumors, mainly uterine, followed by lung and breast, have significantly higher odds of TLS, more so in larger or non-teaching hospitals. There is a need to establish specific management guidelines to prevent these TLS cases that will improve the morbidity and mortality associated with TLS and help build more cost-effective treatment regimens. [Table: see text]

Tumor Lysis Syndrome in Adults with Hematologic Malignancies

Introduction: Tumor lysis syndrome (TLS) is a metabolic complication commonly seen in patients with hematologic malignancies, particularly high-grade non-Hodgkin lymphomas and acute leukemia. It is characterized by biochemical abnormalities that can lead to cardiac, neurological, and renal complications that can be fatal. The purpose of our study is to describe the epidemiology, laboratory profile and the outcome of TLS in order to identify patients at risk, and to implement appropriate prophylactic measures to prevent the clinical repercussions. Material and Methods: This work is a retrospective study of all patients who developed a laboratory TLS in hematologic malignancies according to the classification of Cairo and Bishop over a period of 3 years (from November 2019 to November 2022), and whose data were collected at the adult hematology unit of the Mohammed VI University Hospital of Tangiers. Results: The incidence of TLS among hematologic malignancies identified during this period was 3.7%. The underlying disease was acute leukemia in 10 patients (55.6%) and high-grade lymphoma in eight patients (44.4%). TLS was spontaneous in fifteen cases (83%) and chemotherapy-induced in three cases (17%). All our patients presented with hyperphosphatemia. 94% of cases had hyperuricemia, 44% of cases had hypocalcemia, while 6% of cases had hyperkalemia. Lactate dehydrogenase levels were elevated in all cases. Treatment consisted of hyperhydration and administration of hypouricemic agents in all cases. Three patients received hemodialysis. The outcome was favorable in 83% of cases and 17% of cases died during follow-up. Conclusion: TLS is a severe complication, most often seen in highly proliferative hematologic malignancies. The role of the laboratory remains paramount in the diagnosis of TLS and in the biological monitoring after the implementation of appropriate therapeutic measures.

A rare case of tumour lysis syndrome in multiple myeloma

Tumour lysis syndrome (TLS) is a serious life-threatening complication of cancer chemotherapy which is a constellation of metabolic disturbances that typically occurs during therapy of bulky, rapidly proliferative tumours. TLS is an oncological emergency that causes a significant release of phosphate, potassium, uric acid, and nucleic acids into the blood stream. Incidence of TLS in multiple myeloma is rare. Here we present a case of multiple myeloma who later developed tumour lysis syndrome in its due course which was rare. A 67-year-old male was diagnosed with Multiple myeloma on the basis of M spike, osteolytic lesions and bone marrow analysis. First cycle of chemotherapy with lenalidomide, bortezomib and denosumab was initiated. During the course of follow up he presented to our casualty with complaints of chills and rigor. Based on the biochemical abnormalities a diagnosis of tumour lysis syndrome was made. He received I.V fluids, anti-hyperkalemic measures, allopurinol. He had neutropenic sepsis and went into septic shock and died after multiple resuscitative efforts.

Acute kidney injury in bortezomib-treated patients with multiple myeloma.

The nephrotoxicity of bortezomib, a proteasome inhibitor, has not yet been elucidated, although tumor lysis syndrome (TLS) associated with multiple myeloma (MM) has been reported to increase after introduction of the drug. This study compared the incidence and risk factors for acute kidney injury (AKI) and TLS in patients with MM after bortezomib-based chemotherapy to investigate drug-related nephrotoxicity. From 2006 to 2017, 276 patients who underwent a first cycle of bortezomib-based chemotherapy for MM were identified in a single tertiary hospital. Laboratory TLS was defined according to the Cairo-Bishop definition. Development of AKI was assessed by AKI Network criteria within 7 days of the first chemotherapy. The median (interquartile range) age was 65 (56-72) years, and baseline estimated glomerular filtration rate (eGFR) was 61.3 (34.1-89.1) mL/min/1.73 m2. The incidences of AKI and laboratory TLS were 17% (n=47) and 13% (n=36), respectively. Ten (3.6%) subjects met both AKI and TLS criteria. Multivariate analyses showed that lower eGFR category [30-59, odds ratio (OR) 3.005 (95% confidence interval 1.163-7.976); 15-29, OR 4.225 (1.183-15.000); <15, OR 16.154 (3.831-70.920) vs ≥60, P<.001], lower serum albumin level [per 1 increase, OR 0.479 (0.256-0.871), P=.018], renal amyloidosis [OR 13.039 (4.108-44.041), P<.001] and use of acyclovir during bortezomib treatment [OR 3.689 (1.133-14.469), P=.042] were predictors of AKI. MM stages and β-2-microglobulin were not associated with increased risk of AKI. Regarding laboratory TLS, MM stage and β-2-microglobulin were higher in those with TLS than in others. In multivariate analyses, β-2-microglobulin level [OR 1.204 (1.005-1.461), P=.038] and absence of high-risk chromosome abnormalities [OR 0.143 (0.022-0.588), P=.016] were associated with higher risk of TLS. Development of AKI was often observed in the absence of TLS in patients with MM after treatment with bortezomib. In addition, the risk factors for AKI and TLS varied widely. These findings indicate the potential nephrotoxicity of bortezomib irrespective of TLS in patients with decreased kidney function.

A Retrospective Single-Center Study of Sevelamer Hydrochloride for the Treatment of Hyperphosphatemia in Children With Tumor Lysis Syndrome.

Introduction Tumor lysis syndrome (TLS) is a life-threatening metabolic abnormality. The incidence of TLS depends on the underlying malignancy. In a recent analysis of hematological malignancy, the incidence of clinical TLS in children was 3.8%, laboratory TLS 46.2%, and hyperphosphatemia 32.7%. Sevelamer is effective for the treatment of hyperphosphatemia associated with renal failure; however,there is no clear data that it has the same effect in treating hyperphosphatemiawith TLS. Methods This was a retrospective study among children aged ≤14 years with hematological malignancy who developed TLS and received sevelamer to treat hyperphosphatemia at Princess Norah Oncology Center, King Abdulaziz Medical City (KAMC) in Jeddah from January 2012 to December 2016. Results A total of 34 patients received sevelamer. The majority was male (64%), with a median age of six years. The median sevelamer dose per day was 1600 mg, while the median duration of use was two days. Phosphate level was significantly decreased at different times(24 hours, 48 hours, and 72 hours) during sevelamer usage, p-value <0.001. Conclusion In our study, the use of sevelamer resulted in a significant decrease in phosphate levels. This finding further consolidates the efficacy of sevelamer in treating hyperphosphatemia with TLS. However, further research into the drug's kinetics is recommended.

Incidence of tumor lysis syndrome during induction chemotherapy in pediatric acute lymphoblastic leukemia

Incidence of tumor lysis syndrome during induction chemotherapy in pediatric acute lymphoblastic leukemia

Waveline-001: Updated Results from a Phase 1 Dose Escalation and Cohort Expansion Study of Zilovertamab Vedotin (MK-2140) in Non-Hodgkin Lymphoma

Background: Zilovertamab vedotin (ZV) is a receptor tyrosine kinase-like orphan receptor 1 (ROR1) targeting antibody-drug conjugate comprising zilovertamab, a proteolytically cleavable linker, and the antimicrotubule agent monomethyl auristatin E. ROR1 is a transmembrane protein absent in mature tissues but highly expressed in certain hematologic malignancies, making it an attractive therapeutic target. Safety and efficacy of ZV are being investigated in the phase 1 WAVELINE-001 study (NCT03833180), which is a dose escalation and cohort expansion analysis in patients (pts) with relapsed and/or refractory (R/R) hematologic malignancies. Initial results showed ZV had a tolerable safety profile and promising antitumor activity in R/R non-Hodgkin lymphoma (NHL; Wang M, et al. NEJM Evid. 2021;1[1]). Updated results, including PFS and OS for mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and Richter transformation (RT), are presented. Methods: Eligible pts aged ≥18 years of age, with a histological diagnosis of MCL, DLBCL, or RT; had ECOG PS 0-2; and progression during or relapsed after prior systemic therapy, were included. WAVELINE-001 included 3 dosing schedules. Data from Schedule 1 are presented; Schedules 2 and 3 are ongoing. In Schedule 1, pts received ZV IV at a starting dose of 0.5 mg/kg on day 1 Q3W, increasing to 2.5 mg/kg using an accelerated plus 3 + 3 dose escalation design. Primary end point was determination of the maximum tolerated dose and/or recommended dosing regimen (RDR). Secondary end points included safety, ORR, DOR, PFS, and OS. Results: A total of 54 pts were enrolled in Schedule 1, of which 30 pts were treated at the established RDR of 2.5 mg/kg. At data cutoff (May 18, 2022), median follow-up was 15.3 months (range, 0.5-37.8). Median age was 70.0 yrs, 57% of pts were male, 48% had an ECOG PS of 0, 65% had received ≥3 prior therapies, 80% had NHL (FL, n=3; DLBCL, n=15; MCL, n=17; MZL, n=1; RT, n=7), and 20% had other disease (AML, n=3; CLL/SLL, n=7; mixed histology, n=1). MCL pts had received a median (range) of 4 (1-9) prior lines of therapy. All MCL pts received prior BTKi therapy, and none had prior CAR-T or CAR-NK therapy. 59% of MCL pts were Ann Arbor stage IV. DLBCL pts received a median (range) of 4 (1-7) prior lines of therapy, 67% of pts had received prior CAR-T or CAR-NK therapy; 47% of pts were GCB, and 33% were ABC subtype. Five pts (71%) with RT had the DLBCL subtype. No pts with RT received autologous stem cell transplant and received a median (range) of 3 (1-10) prior therapies. Any-cause adverse events (AEs) occurred in 52 (96%) pts. Any-grade treatment-related AEs (TRAEs) occurred in 40 pts (74%); most common (≥20%) were peripheral neuropathy (46%), neutrophil count decreased (35%), fatigue (35%), nausea (28%), and diarrhea (20%). Decreases in hemoglobin and platelet count occurred in 13% and 11% of pts, respectively. Grade 3-4 TRAEs occurred in 28 pts (52%), most commonly neutrophil count decreased (33%), platelet count decreased (11%), and peripheral neuropathy (7%). AEs of special interest regardless of causality occurred in 76% of pts; most common were hematopoietic cytopenia (56%) and peripheral neuropathy (48%). For pts experiencing peripheral neuropathy, most cases were grade 1/2 (41%); 7% were grade 3. Median (range) time to onset of first peripheral neuropathy was 49 (1-162) days. No incidences of tumor lysis syndrome or infusion reactions occurred and no grade 5 TRAEs occurred. AEs led to ZV discontinuation in 12 pts (22%) and interruption or reduction in 24 (44%). ORR was 33% (5/15; 95% CI, 12-62; 3 CR/2 PR) in DLBCL, 53% (9/17; 95% CI, 28-77; 2 CR/7 PR) in MCL, and 57% (4/7; 95% CI, 18-90; 1 CR/3 PR) in RT. No responses were seen among the other indications treated. Median DOR (range) was 4.6 months (2.9-21.5) for DLBCL, 10.0 (0-20.3) for MCL, and 2.8 (0-2.8) for RT. Median PFS (95% CI) was 3.9 months (0.5-7.0) for DLBCL, 11.4 (4.0-NE) for MCL, and 4.7 (0.7-NE) for RT. Median OS (95% CI) was 9.1 months (1.0-NE) for DLBCL, 18.0 (7.1-NE) for MCL, and 24.0 (2.7-NE) for RT. Among 12 pts with NHL (10 DLBCL and 2 RT) who had undergone prior CAR-T/CAR-NK therapy, ORR was 33% (4/12; 95% CI, 10-65). Conclusions: Updated results from WAVELINE-001 support prior analyses showing ZV had a tolerable safety profile and promising response rates, and favorable PFS and OS among heavily pre-treated pts with DLBCL, MCL, and RT, including pts who had received prior CAR-T/CAR-NK therapy.

Outcomes of Tumor Lysis Syndrome in Hospitalized Patients: A Retrospective Cohort Study from National Inpatient Sample 2016-2019

Background: Tumor lysis syndrome (TLS) is an oncologic emergency caused by rapid cell lysis spilling intracellular contents (potassium, phosphate, and nucleic acids) into the systemic circulation leading to hyperkalemia, hyperphosphatemia, secondary hypocalcemia, hyperuricemia, and acute kidney injury. We aim to study outcomes like in-hospital mortality, length of stay (LOS) and associated complications among TLS patients. Methods: This is a retrospective cohort study from TLS hospitalizations between January 1, 2016, and December 31, 2019, using the 2016-2019 National Inpatient Sample (NIS), the largest all-payer public database of hospital care data in the United States. Our study sample included, TLS hospitalizations with age 18 years or older, using the ICD 10 diagnosis codes validated in previous studies. Results: From 2016 to 2019, the incidence rate of TLS was 36 per 100,000 (N=10,277) hospitalizations. Among TLS admissions, 36.9% (n= 3794) were females and mean age was 63±15.5 years (P<0.001). Moreover, 67.5% were Whites, 14.7% were Blacks, 9.4% were Hispanics, and 3.7% were Asians. A total of 2494(47%) hospitalizations had a Charlson Comorbidity index (CCI) of three or higher. TLS hospitalizations were complicated by sepsis (10.6%, N=1089), Cardiac arrest (2.9%, N=298), AKI (68.8%, N=7072), ARDS (0.6%, N=64, requirement for dialysis (8.8%, N=906), GI bleed (5.5%, N=568), Non-traumatic brain hemorrhage (1.4%, N=142), Hyperkalemia (29%, N=2976), Hypocalcemia (10%, N=1042), requirement of mechanical ventilation (11%, N=1130). Mean length of stay was 13.7 days±14.6. Multivariate regression analysis showed that, the predictors for increased in-hospital mortality were GI bleed(aOR: 1.43; 95% CI: 1.16, 1.7; p=0.001), Sepsis (aOR: 2.77; 95% CI: 2.35, 3.25; p<0.001), AKI (aOR: 2.89; 95% CI: 2.49, 3.35; p<0.001), hyperkalemia (aOR: 1.54; 95% CI: 1.37, 1.73; p<0.001) after controlling for age, race ,gender, regional location of the hospital, and income. Females have higher in hospital mortality from TLS compared to males (aOR: 1.22; 95% CI: 1.09, 1.36; p=0.001). From 2016-2019, the annual incidence of TLS per 100,000 hospitalizations has been increasing at 28.6 in 2016, 33.3 in 2017, 38.3 in 2018 and 44.3 in 2019 (p-trend<0.001). Conclusion: Increased incidence of in hospital mortality could be attributed to GI bleed, hyperkalemia, sepsis, AKI. The annual incidence of TLS is rising every year.

Real-world analysis of tumor lysis syndrome in patients started on venetoclax combination for acute myeloid leukemia.

Venetoclax is utilized with low-dose cytarabine or a hypomethylating agent for the treatment of acute myeloid leukemia. Clinical trials report a risk of tumor lysis syndrome and the package insert recommends a venetoclax dose ramp-up at the initiation. The purpose of this study was to evaluate the risk of tumor lysis syndrome in a large population of patients with acute myeloid leukemia outside of a clinical trial and evaluate the incidence of hospital-acquired complications during inpatient ramp-up. We performed a retrospective study of adult patients with acute myeloid leukemia receiving venetoclax with a hypomethylating agent or low-dose cytarabine. The primary outcome was the incidence of tumor lysis syndrome. Secondary outcomes included risk factors for tumor lysis syndrome, length of admission, and incidence of hospital-acquired complications. One hundred thirteen patients were included. Although all patients were given some form of prophylaxis, the incidence of tumor lysis syndrome was 8.8%. All were laboratory tumor lysis syndrome; one with hyperuricemia, nine with hypocalcemia, and ten with hyperphosphatemia. Six patients received sevelamer. Tumor lysis syndrome was resolved in all cases. No clinical tumor lysis syndrome occurred. Hepatic dysfunction, tumor lysis syndrome high-risk stratification, higher baseline white blood cell count, and lactate dehydrogenase levels were more common in the tumor lysis syndrome group. Hospital-acquired complications reached 13% in those directly admitted for dose ramp-up. Tumor lysis syndrome was uncommon and manifested as minor lab abnormalities. White blood cell count continues to be an indicator of risk for tumor lysis syndrome. Those who present with an elevated white blood cell or are otherwise at high risk for tumor lysis syndrome should be admitted for ramp-up. Otherwise, initiation and monitoring of venetoclax are feasible in the outpatient setting.

Tyrosine kinase inhibitors and tumor lysis syndrome in hematologic malignancies: A systemic review

Effective treatments for hematologic malignancies include therapies that target tyrosine kinase (TK) signaling pathways. Tumor lysis syndrome (TLS) is an oncologic emergency that can occur due to rapid turnover following the initiation of treatments for hematologic malignancy. The incidence of TLS is under-reported and it is unclear as to whether TK inhibitors (TKIs) are associated with TLS. To conduct a systematic review to determine the incidence of TLS with TKIs. A search was performed using EMBASE, MEDLINE, and Web of Science electronic databases, as well as a manual search of the American Society of Hematology and American Society of Clinical Oncology abstract databases. Keywords included: "tumor lysis syndrome," "tyrosine kinase inhibitors," "lymphoma," and "leukemia." We identified a total of 57 publications that commented on the incidence of TLS with TKIs for hematologic malignancy. Thirty-nine of those publications reported TLS as an adverse event. TLS was described as an adverse event among essentially all the subclasses of TKIs that are used to manage hematologic malignancies. The overall number of articles commenting on TLS as an adverse event is sparse and there needs to be more transparency regarding the incidence of TLS when employing newer targeted therapies. Physicians should consider the risk of TLS on an individual basis and the added risk of TLS when using TKIs to treat hematologic malignancy.

Tumor lysis syndrome and infectious complications during treatment with venetoclax combined with azacitidine or decitabine in patients with acute myeloid leukemia

Venetoclax (Ven) in combination with azacitidine or decitabine (hypomethylating agent; HMA) is the standard-of-care treatment for older (≥75 years) or intensive chemotherapy ineligible adults with newly diagnosed acute myeloid leukemia (AML). Tumor lysis syndrome (TLS) and infectious complications are two of the most concerning associated adverse events. We studied the real-world incidence and outcomes of these adverse events with HMA/Ven in AML patients. Our retrospective analysis included 106 patients (median age 70 years). Of these, 61 (58%) received HMA/Ven in frontline setting while 45 (42%) received in salvage setting. 19 (18%) met laboratory criteria for TLS, five (5%) developed clinical TLS (acute kidney injury). The median time to develop TLS was 2 days (range −2 to 4). During cycle 1, 29 patients (27%) were diagnosed with febrile neutropenia while 26 (25%) developed new infections. Median time to development of new infection was 10 days (1−25). Pneumonia was the most common infection (8%). Febrile neutropenia and/or new infection during cycle 1 was associated with poorer median overall survival compared to those without these complications (4.9 months vs 11.6 months; p = 0.03). In conclusion, incidence of TLS and infections was high in our cohort during initiation of HMA/Ven therapy. This data emphasizes the need for closer monitoring in these patients, especially during the first 7–10 days of treatment, which is often achieved in the inpatient setting.