Absolute lymphocyte count in patients with glioblastoma treated with temozolomide chemoradiation.

e13564 Background: Standard glioblastoma (GBM) management includes radiotherapy, chemotherapy, and steroids; all of which can result in immunosuppression and a low absolute lymphocyte count (ALC). Previous literature identified an association between low CD4 and worse progression free survival (PFS) and overall survival (OS). There remains a lack of research addressing predictors of immunosuppression in patients with GBM. The primary objective of this study is to identify the degree of immunosuppression, measured by ALC, in GBM patients receiving concurrent temozolomide chemoradiation (CRT). Secondary objectives include associations between ALC, PFS, and OS, and whether there are any predictors of immunosuppression in patients with GBM. Methods: We retrospectively reviewed 231 newly diagnosed GBM patients who underwent surgery followed by standard of care CRT. We also analyzed the association between ALC and age, sex, MGMT methylation status, and extent of surgical resection. ALC was collected at the time of surgery, CRT start date, and two, four, six, and ten weeks post-CRT start date. Common Terminology Criteria for Adverse Events (CTCAE) protocol version 5.0 was then used to grade low ALC as grade 0, 1, 2, 3, or 4. Results: Of the 231 patients analyzed, 139 were males, 74 underwent gross total resection of the tumor, 129 patients were less than 65 years, and 79 (42.5%) were MGMT methylated. 37 patients had grade 3-4 low ALC. In a univariate analysis, grade 3-4 low ALC at 4 weeks (±14 days) post-CRT start was associated with higher mortality (HR 1.54, P = 0.028) but had no significant association with PFS (HR 1.22, P = 0.29). Logistic regression analysis was used to identify risk factors for grade 3-4 low ALC and its association with survival. None of the risk factors that we tested such as age, gender, type of surgery, or molecular markers including MGMT, IDH, or EGFR were associated with low ALC. Conclusions: Our study demonstrated that patients with ALC grade 3 or 4 at 4 weeks (±14 days) of CRT had a significantly higher mortality (HR 1.54, P = 0.028) but had no significant association with PFS (HR 1.22, P = 0.29).

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Risk Model Predictive of Severe Anemia Requiring RBC Transfusion After Chemotherapy in Pediatric Solid Tumor Patients

Journal of Clinical Oncology ◽

10.1200/jco.2003.09.121 ◽

2003 ◽

Vol 21 (22) ◽

pp. 4235-4238 ◽

Cited By ~ 9

Author(s):

Perrine Marec-Berard ◽

Jean Yves Blay ◽

Matthias Schell ◽

Murielle Buclon ◽

Corrine Demaret ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Lymphocyte Count ◽

Risk Model ◽

Pediatric Population ◽

Performance Status ◽

Univariate Analysis ◽

Absolute Lymphocyte Count ◽

The Difference ◽

Rbc Transfusion

Purpose: Severe anemias requiring RBC transfusions is a frequent complication of chemotherapy. A model elaborated by Ray-Coquard et al in adults pointed to three independent risk factors for RBC transfusion: performance status (PS) more than 1, hemoglobin less than 12 g/dL, and prechemotherapy absolute lymphocyte count (ALC) ≤ 700/μL. This model is tested on a pediatric population.Patients and Methods: One hundred nineteen children with solid tumors consecutively admitted for conventional chemotherapy throughout 1 year were included. The study end point was the RBC-transfusion risk in the month following chemotherapy. Only one course was considered for each patient. Age, sex, number of courses, platinum-containing regimens, PS, and hemoglobin and lymphocyte count at day 1 were tested in univariate and multivariate analyses.Results: Thirty-one (26%) of 119 children required RBC transfusion within 31 days of chemotherapy. Three factors correlated to transfusion risk in the univariate analysis: PS more than 1 (P < .001), hemoglobin less than 12 g/dL (P = .007), and pretreatment ALC ≤ 700/μL (P < .001). In the multivariate analysis, hemoglobin less than 12 g/dL, PS more than 1, and ALC ≤ 700/μL were identified as independent factors predicting RBC transfusion. The calculated probability of receiving RBC transfusion within 31 days of chemotherapy was high with three risk factors (96%), intermediate with two risk factors (53% to 77%), low with one risk factor (10% to 26%), and very low when no risk factor was present (2%). The difference of transfusion needs was significant (P < .001).Conclusion: The risk model elaborated for adults may also segregate children at high risk of postchemotherapy RBC transfusion, thus facilitating assessment of risk of transfusion and/or prophylactic erythropoietin support.

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Immune Mediated Cytopenia's Following Cord Blood Transplantation for Hurler's Syndrome: A Failure of Pre-Transplant Immune Suppression

Blood ◽

10.1182/blood-2018-99-112995 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3374-3374

Author(s):

David Deambrosis ◽

Ryan Hum ◽

Prashant Hiwarkar ◽

Kay Poulton ◽

Denise Bonney ◽

...

Keyword(s):

Risk Factors ◽

Lymphocyte Count ◽

Cord Blood Transplantation ◽

Univariate Analysis ◽

Significant Risk ◽

Absolute Lymphocyte Count ◽

Graft Versus Host ◽

Blood Transplantation ◽

Hurler’S Syndrome ◽

Autoimmune Cytopenia

Abstract Background: Hurler's syndrome is the most severe phenotype of Mucopolysaccharidosis 1 (MPS1H) with severe deficiency of the lysosomal enzyme alpha-L-iduronidase causing heparan and dermatan sulfate accumulation, CNS and somatic manifestations and premature death. Haematopoeitic Stem Cell Transplant (HSCT) alters the disease phenotype and prevents early death, and is standard of care in this condition. The use of an established 'donor hierarchy' recommending Unrelated Cord Blood Transplantation (UCBT) in the absence of a HLA-matched, non-carrier sibling, has resulted in improved engrafted and surviving rates and better post-enzyme levels with improved somatic and CNS clinical outcomes. However, UCBT for malignant and non-malignant conditions has led to high rates of post-transplant autoimmune disease, most frequently Autoimmune Cytopenia (AIC). We report a large cohort of MPS1H patients receiving busulfan-based UCBT and show that AIC is a frequently encountered complication of treatment with significant associated morbidity and we identify important risk factors for its occurrence. Methods: This was a retrospective observational study of patients undergoing first UCBT for Hurler's Syndrome at the Royal Manchester Children's Hospital between 30th September 2004 and 15th March 2018. An episode of AIC was defined as an episode of single or multi-lineage cytopenia occurring post-engraftment, confirmed by the presence of antibodies or diagnosed on the basis of clinical, biochemical and pathologic features. All patients received pK targeted busulfan to achieve myeloablative levels between 80-90 mg/L x hr. Conditioning between 2004 and May 2010 was with Busulfan and Cyclophosphamide (BuCy), and Fludarabine and Busulfan (FluBu) thereafter based on the reported equivocal efficacy and favourable toxicity profile of FluBu conditioning. All patients received serotherapy with Anti-Thymocyte Globulin (ATG) 10mg/kg for In Vivo T-Cell depletion. Timing of ATG was either distal (day -4 to -1) or proximal (day - 9 to -6) in accordance with international consensus at the time. Variables assessed in statistical analysis were conditioning drugs, ATG timing, Absolute Lymphocyte Count pre-conditioning, age-at-transplant, Graft-versus-Host Disease (GVHD) and Total Nucleated Cell dose. Results and Discussion: Thirty-six patients underwent first UCBT for Hurler's Syndrome. There were 8 episodes of AIC (22%), with median onset post-UCBT of 66 days (range 22-236 days). The median number of therapies required was 4 (range 0-8), with duration of illness ranging from 10 to 215 days. There were no deaths, though there were 2 episodes of life-threatening bleeding. Absolute Lymphocyte Count pre-conditioning (p=0.004), FluBu conditioning (p=0.03) and use of proximal-ATG (p=0.016) were significant risk factors for AIC in univariate analysis(see figure 1). Absolute Lymphocyte Count pre-conditioning was the most significant predictor in multivariable analysis (AOR 5.796, CI 0.921-36.474). This confirms that AIC is a frequent, serious but survivable complication of UCBT for Hurler's Syndrome. This data indicates that the balance between recipient immunity and graft immunity impacts AIC risk and severity, mandating a larger international review of registry data to define the frequency of AIC in this population, and an analysis of the risk factors that predispose to it. By better defining these risk factors, we can identify patients in whom conditioning might be altered to reduce risk. Figure 1. Univariate analysis of variables predicting an episode of Autoimmune Cytopenia. ALC (p=0.004), ATG timing (0.016) and Conditioning drugs (p=0.032) were significant risk factors. GVHD= Graft-versus-Host Disease ATG= Anti-Thymocyte Globulin Disclosures Wynn: Orchard SAB: Membership on an entity's Board of Directors or advisory committees; Orchard Therapeutics: Equity Ownership; Chimerix: Research Funding; Genzyme: Honoraria; Bluebird Bio: Consultancy; Orchard Therapeutics: Consultancy; Chimerix: Consultancy.

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QOLP-04. THE KETOGENIC DIET PLUS STANDARD CARE FOR RECENTLY DIAGNOSED GLIOBLASTOMA: A PHASE 1 SAFETY AND FEASIBILITY TRIAL

Neuro-Oncology ◽

10.1093/neuonc/noab196.725 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi183-vi183

Author(s):

Jethro Hu ◽

L J Amaral ◽

Gillian Gresham ◽

Thomas Nelson ◽

Amelia Welborn ◽

...

Keyword(s):

Ketogenic Diet ◽

Phase 1 ◽

Progression Free Survival ◽

Standard Of Care ◽

Primary Objective ◽

Feasibility Trial ◽

Phase 2 Trial ◽

Related Quality ◽

Health Related ◽

Grade 3

Abstract INTRODUCTION There is abundant interest in the potential therapeutic and supportive role of a ketogenic diet (KD) for glioblastoma patients. We conducted a single-arm phase 1 trial to assess the safety and feasibility of KD plus standard-of-care (SOC) in glioblastoma patients (NCT03451799). METHODS Adults within 3 months of diagnosis participated in a 16-week intervention of a classic 3:1 KD (grams fat : grams carbohydrate + protein) with dietitian support. Blood glucose and ketone levels were assessed twice daily (Keto-Mojo), with remote monitoring of daily weight and activity (Fitbit). The primary objective was to assess safety (weight stability, CTCAE) and feasibility (maintaining ketosis > 0.3mM for > 50% of study period). Secondary objectives included assessments of progression-free survival (PFS), overall survival (OS), health-related quality of life (HRQOL), and cognition (MoCA). RESULTS From 04/2018-02/2021, 14 patients were evaluable: female:male, 8:6, median age 55 years, KPS 80, BMI 24.5. MGMT promoter methylation: 6 present, 7 absent, 1 indeterminate. Adherence to KD was high, with all patients maintaining ketosis ( > 0.3mM) > 50% and 11 patients maintaining ketosis > 85% of study days. Adverse events (> Grade 2) potentially attributable to KD: appetite loss (Grade 2: 2); fatigue (Grade 2: 5); flu-like symptoms (Grade 2: 1); constipation (Grade 2: 5, Grade 3: 1). No patients were removed from study for safety reasons. HRQOL was stable, with improvements in role function (not statistically significant). MoCA score improved in 10/14 patients. Median PFS and OS from KD initiation were 11.7 and 29.1 months, respectively. CONCLUSION Our findings suggest that a supervised KD plus SOC is safe and feasible in glioblastoma patients. KD was well-tolerated with encouraging trends in HRQOL and cognition. PFS and OS in this small trial compare favorably to historical control. A multicenter phase 2 trial powered to assess efficacy is planned.

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Low platelet counts in patients with glioblastoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e13565 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e13565-e13565

Author(s):

Assad Ali ◽

Addisson Barnett ◽

Anas Saeed Bamashmos ◽

Hong Li ◽

Wei (Auston) Wei ◽

...

Keyword(s):

Platelet Count ◽

Univariate Analysis ◽

Methylation Status ◽

Concurrent Chemotherapy ◽

Primary Objective ◽

Newly Diagnosed ◽

Analysis Model ◽

Time Of Surgery ◽

Platelet Counts ◽

Start Date

e13565 Background: Radiotherapy and concurrent chemotherapy with Temozolomide (TMZ) have myelosuppressive effect, and thrombocytopenia is commonly seen in this patient population seen in 5-10% of glioblastoma (GBM) patients. There is a lack of data analyzing the thrombocytopenia and it’s on the progression free survival (PFS) or overall survival (OS) of these patients. The primary objective of this study was to identify the degree of thrombocytopenia in newly diagnosed GBM patients receiving concurrent TMZ based chemoradiation (CRT). Secondary objectives included associations between thrombocytopenia PFS, and OS. Methods: We retrospectively reviewed 484 newly diagnosed GBM patients who underwent surgery followed by standard of care CRT. We also analyzed the association between platelet counts and age, sex, MGMT methylation status, and extent of surgical resection. Platelet count was collected at the time of surgery, CRT start date, and two, four, six, and ten weeks post-CRT start date. Patients were grouped into quartiles according to their platelets count. Results: Of the 484 patients collected, 308 were males, 139 had gross total resection of the tumor, 229 patients were older than 65 years, and 171 (42.1%) were MGMT methylated. In a univariate analysis, a platelet count less than 180,000 (lowest quartile) was associated with higher mortality (HR 1.63, P < 0.001) but had no significant association with PFS (HR 1.16, P = 0.48). Among the 118 patients who had platelet count lower than 180,000, 4 had platelets count less than 100,000 necessitating their TMZ to be stopped during CRT. In a multivariate analysis model adjusting for age, gender, MGMT status, and type of surgery, platelet counts less than 180,000 was also associated with significantly higher mortality (HR 1.60, P < 0.001). Conclusions: Our study concluded that patients who had platelet counts less than 180,000 at the time of surgery or CRT with TMZ had significantly higher mortality (HR 1.60, P < 0.001) but had no association with PFS (HR 1.16, P = 0.48).[Table: see text]

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CTIM-15. PRELIMINARY RESULTS OF A PHASE II STUDY OF NIVOLUMAB WITH HYPOFRACTIONATED RE-RADIATION AND BEVACIZUMAB FOR RECURRENT MGMT METHYLATED GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noaa215.149 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii36-ii36

Author(s):

Christian Grommes ◽

Minesh Mehta ◽

Alexandra Miller ◽

Mariza Daras ◽

Anna Piotrowski ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Study ◽

Checkpoint Inhibitors ◽

Single Agent ◽

Progression Free Survival ◽

Standard Of Care ◽

Disease Recurrence ◽

Primary Objective ◽

Significant Finding ◽

Trial Treatment

Abstract Standard of standard of care for glioblastoma (GBM) remains unsatisfactory with universal disease recurrence and a median survival of < 2 years. Immune checkpoint inhibitors (ICI) have shown limited single-agent activity in GBM thus far. GBMs with methylated MGMT promoter and no baseline corticosteroid dependence may be most likely to derive benefit from ICI. The combination of ICIs with radiation has shown promising activity in other human cancers. Combining nivolumab and re-RT/bevacizumab in GBM may augment ICI activity through immunogenic effects of radiation, may reduce the risk of radiation necrosis by addition of bevacizumab at the time of radiation, and may reduce the need for corticosteroids. In this multicenter phase II study, nivolumab is combined with re-irradiation and optional concurrent bevacizumab followed by nivolumab in patients with first recurrence of IDH-wildtype and MGMT methylated glioblastoma. Primary objective is to improve 1-year overall survival (OS) from 33 (based on EORTC 26101) to 50%. Nine-three patients are required to show a significant finding with an α of 0.05 and 81% power. Thirteen of 93 patient (14%) have been enrolled with a median age of 59 (range 42–71) with a median KPS of 90 (range 70–90). Treatment has been tolerated well without any grade ≥ 4 toxicities and only one grade 3 (amylase elevation). The most common adverse events were pruritus and hypothyroidism in 3/13 (23%). The median progression-free survival (PFS) is 7 months with a 6months PFS of 55.6%. The 12months OS is 66.7%. Patients with recurrent MGMT methylated, IDH-wildtype glioblastoma tolerate trial treatment with acceptable toxicities. Clinical efficacy in the first patients enrolled shows a promising effect. Enrollment is ongoing.

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The combination of venetoclax, lenalidomide, and rituximab in patients with newly diagnosed mantle cell lymphoma induces high response rates and MRD undetectability.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.7505 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 7505-7505

Author(s):

Tycel Jovelle Phillips ◽

Alexey Valeryevich Danilov ◽

David Alan Bond ◽

Alex Francisco Herrera ◽

Kami J. Maddocks ◽

...

Keyword(s):

Phase 1 ◽

Safety Data ◽

Standard Of Care ◽

Primary Objective ◽

Clinical Activity ◽

Newly Diagnosed ◽

Grade 5 ◽

Unrelated Condition ◽

Mantle Cell ◽

Grade 3

7505 Background: MCL is a rare lymphoma without a standard of care but several regimens have demonstrated clinical activity, the majority based on traditional chemotherapy. We hypothesized that adding venetoclax (V) to R2 would be safe and effective in MCL pts irrespective of age, morphology or stage. Here we present safety and efficacy data from the on-going phase 1b study of R2 + V in pts with newly diagnosed MCL. Methods: This multi-center phase 1 study (NCT03523975) enrolled pts aged ≥18 yrs with untreated MCL. The primary objective was to characterize the safety and tolerability of R2 + V and determine the MTD. During induction (12 months (m)) pts received lenalidomide (L) 20 mg daily on day 1-21, Rituximab (R) was given weekly during c1 then on day 1 of every even cycle, V was escalated over 4 weeks to 400 mg beginning day 8. Each cycle is 28 days (d). The DLT period was 42 d beginning C1D8. In maintenance, R every 8 weeks for 36m, L at 10 mg or half of last dose during induction for 24 m and V for minimum 12 m. No pts have been transplanted. Pts with progression (PD) came off study. MRD was analyzed in parallel with scans during induction by clonoSEQ assay (Adaptive Biotechnologies). Results: As of Feb. 1st, 2021, we have enrolled all 28 planned pts on study. Pt characteristics/responses are summarized in Table. Among the 28 pts who have received at least one dose, the median treatment duration so far is 278d (IQR 170-560), with 24 pts still on treatment (Tx). 1 pt is off from a unrelated condition. All pts escalated to V 400 mg w/o any DLTs noted. Treatment-emergent adverse events (TEAEs) were reported in 100% of pts, and grade 3+ TEAEs were reported in 26 (93%) patients. The most common all-grade TEAEs (≥50% of pts), regardless of relationship to study Tx, were fatigue, neutropenia and diarrhea. Grade ≥3 TEAEs reported in ≥50% pts were neutropenia (68%) and thrombocytopenia (50%). No pts have withdrawn or d/c Tx due to AEs. There was one grade 5 event, in a non-evaluable pt, related to a PE that occurred prior to DLT period. In the 28 evaluable pts the ORR (CR/PR) was 96% (27/28 pts) with CR/CRu of 89%. Of the responding pts, two had PD, one w/ CR and one w/ PR. All pts with PD had baseline TP53 mutation. MRD testing was successful in all pts. At time of submission 20 of 28 (71%) were MRD - at 10-6. Conclusions: Interim results show that at the MTD the combination of V 400 mg daily, L 20 mg, with R is safe with a manageable toxicity profile and a high ORR and MRD - in pts with newly diagnosed MCL. Safety data is consistent with the AE profile noted for each drug without any unexpected or unique AEs. Updated results including BH3 profiling will be presented at the meeting. Clinical trial information: NCT03523975. [Table: see text]

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Salvage immune checkpoint inhibitor (ICI) plus tyrosine kinase inhibitor (TKI) combination therapy for metastatic renal cell carcinoma (mRCC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16567 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16567-e16567

Author(s):

Anish B. Parikh ◽

Sarah P. Psutka ◽

Yuanquan Yang ◽

Katharine Collier ◽

Abdul Miah ◽

...

Keyword(s):

Combination Therapy ◽

Immune Checkpoint Inhibitor ◽

Kinase Inhibitor ◽

Objective Response ◽

Progression Free Survival ◽

Standard Of Care ◽

Free Survival ◽

Kaplan Meier ◽

Grade 3 ◽

Combination Regimens

e16567 Background: ICI/TKI combinations are a new standard of care for the initial treatment (tx) of mRCC. Efficacy and toxicity of such combination regimens beyond the first-line (1L) setting remain unknown. Methods: We retrospectively reviewed charts for adult patients (pts) receiving an ICI/TKI combination in any line of tx for mRCC of any histology at one of two academic centers as of May 1, 2020. ICIs included pembrolizumab (Pm), nivolumab (Ni), ipilimumab (Ip), or avelumab (Av); TKIs included sunitinib (Su), axitinib (Ax), pazopanib (Pz), lenvatinib (Ln), or cabozantinib (Ca). Clinical data including pt demographics, histology, International mRCC Database Consortium (IMDC) risk group, tx history, and ICI/TKI tx and toxicity details were recorded. Outcomes included objective response rate (ORR), median progression-free survival (mPFS), and safety, analyzed via descriptive statistics and the Kaplan-Meier method. Results: Of 85 pts, 69 (81%) were male and 67 (79%) had clear cell histology. IMDC risk was favorable (24%), intermediate (54%), poor (20%), and unknown (2%). 39% had ICI/TKI tx in the 1L setting. ICI/TKI regimens included Pm/Ax (33%), Ni/Ca (25%), Ni/Ax (20%), Av/Ax (11%), Ni/Ip/Ca (8%), Ni/Su (2%), and Ni/Ln (1%). ORR and mPFS stratified by line of tx and prior tx are shown in the table. Of 52 pts who received ICI/TKI tx as salvage (after 1L), 52% had a grade 3 or higher (≥G3) adverse event (AE), of which the most common were anorexia (13.5%), diarrhea and hypertension (11.5% each), and fatigue (9.6%). 65% of pts on salvage ICI/TKI tx stopped tx for progression/death, while 16% stopped tx for ≥G3 AE. ≥G3 AE rates by line of tx were 62.5% (2L), 50% (3L), and 45% (≥4L). Conclusions: ICI/TKI combination therapy is effective and safe beyond the 1L setting. Prior tx history appears to impact efficacy but has less of an effect on safety/tolerability. These observations will need to be confirmed in prospective studies.[Table: see text]

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Basic Predictive Risk Factors for Cytokine Storms in COVID-19 Patients

Frontiers in Immunology ◽

10.3389/fimmu.2021.745515 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sergey G. Shcherbak ◽

Anna Yu Anisenkova ◽

Sergei V. Mosenko ◽

Oleg S. Glotov ◽

Alexander N. Chernov ◽

...

Keyword(s):

Risk Factors ◽

Lymphocyte Count ◽

Absolute Lymphocyte Count ◽

Early Warning Score ◽

Positive Test ◽

City Hospital ◽

Cytokine Storm ◽

Positive Test Result ◽

Test Result ◽

D Dimer

ObjectiveA critical role in coronavirus disease 2019 (COVID-19) pathogenesis is played by immune dysregulation that leads to a generalized uncontrolled multisystem inflammatory response, caused by overproduction of proinflammatory cytokines, known as “a cytokine storm” (CS), strongly associated with a severe course of disease. The aim of this study is to identify prognostic biomarkers for CS development in COVID-19 patients and integrate them into a prognostic score for CS-associated risk applicable to routine clinical practice.Materials and MethodsThe authors performed a review of 458 medical records from COVID-19 patients (241 men and 217 women aged 60.0 ± 10.0) who received treatment in the St. Petersburg State Budgetary Institution of Healthcare City Hospital 40 (City Hospital 40, St. Petersburg), from Apr. 18, 2020 to Nov. 21, 2020. The patients were split in two groups: one group included 100 patients with moderate disease symptoms; the other group included 358 patients with progressive moderately severe, severe, and extremely severe disease. The National Early Warning Score (NEWS) score was used alongside with clinical assessment, chest computed tomographic (CT) scans, electrocardiography (ECG), and lab tests, like ferritin, C-reactive protein (CRP), interleukin (IL)-6, lactate dehydrogenase (LDH), and D-dimer.ResultsThe basic risk factors for cytokine storms in COVID-19 patients are male gender, age over 40 years, positive test result for replicative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, absolute lymphocyte count, dynamics in the NEWS score, as well as LDH, D-dimer, ferritin, and IL-6 levels. These clinical and instrumental findings can be also used as laboratory biomarkers for diagnosis and dynamic monitoring of cytokine storms. The suggested prognostic scale (including the NEWS score dynamics; serum IL-6 greater than 23 pg/ml; serum CRP 50 mg/L or greater; absolute lymphocyte count less than 0.72 × 109/L; positive test result for replicative coronavirus (SARS-CoV-2) RNA; age 40 years and over) is a useful tool to identify patients at a high risk for cytokine storm, requiring an early onset of anti-inflammatory therapy.

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Assessment of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) cohort by agent in the phase 3 ASCENT study of patients (pts) with metastatic triple-negative breast cancer (mTNBC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.1077 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 1077-1077

Author(s):

Joyce O'Shaughnessy ◽

Kevin Punie ◽

Mafalda Oliveira ◽

Filipa Lynce ◽

Sara M. Tolaney ◽

...

Keyword(s):

Single Agent ◽

Objective Response ◽

Progression Free Survival ◽

Standard Of Care ◽

Antibody Drug Conjugate ◽

Phase 3 ◽

Chemotherapy Agent ◽

Recist 1.1 ◽

Duration Of Response ◽

Grade 3

1077 Background: In pts with pretreated mTNBC, standard-of-care chemotherapy is associated with low objective response rates (ORRs) and short median progression-free survival (PFS). SG is an antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. SG received accelerated FDA approval for treatment of pts with mTNBC who have received ≥2 prior therapies for metastatic disease. The confirmatory phase 3 ASCENT study (NCT02574455) in pts with relapsed/refractory mTNBC demonstrated a significant survival benefit of SG over TPC (median PFS: 5.6 vs 1.7 mo, HR 0.41, P< 0.0001; median overall survival [OS]: 12.1 vs 6.7 mo, HR 0.48, P< 0.0001) with a tolerable safety profile. Here we summarize efficacy results for SG vs each TPC agent in ASCENT to examine how each TPC agent performed individually. Methods: Pts had mTNBC refractory to or progressing after ≥2 prior standard chemotherapy regimens. Pts were randomized 1:1 to receive SG (10 mg/kg intravenously on days 1 and 8, every 21 days) or single-agent TPC (eribulin, vinorelbine, capecitabine, or gemcitabine). Primary endpoint was PFS per RECIST 1.1 by independent review in brain metastases-negative (BMNeg) pts. Secondary endpoints were ORR per RECIST 1.1, duration of response, OS, and safety. Outcomes for each of the agents in the TPC arm were analyzed and compared with SG. Results: Of 529 pts enrolled, 468 were BMNeg. Among pts in the TPC cohort (n = 233), eribulin was the most commonly chosen chemotherapy (n = 126), followed by vinorelbine (n = 47), capecitabine (n = 31), and gemcitabine (n = 29). Treatment with eribulin, vinorelbine, capecitabine, and gemcitabine resulted in shorter median PFS vs SG (2.1, 1.6, 1.6, and 2.7 vs 5.6 mo, respectively); similar results were observed for median OS (6.9, 5.9, 5.2, and 8.4 vs 12.1 mo), ORR (5%, 4%, 6%, and 3% vs 35%), and clinical benefit rate (CBR; 8%, 6%, 10%, and 14% vs 45%). Key grade ≥3 treatment-related adverse events (TRAEs) with TPC overall vs SG included neutropenia (33% vs 51%), leukopenia (5% vs 10%), fatigue (5% vs 3%), and anemia (5% vs 8%). Key grade ≥3 TRAEs with eribulin vs SG included neutropenia (30% vs 51%), leukopenia (5% vs 10%), fatigue (5% vs 3%), anemia (2% vs 8%), and peripheral neuropathy (2% vs none), respectively. The safety profiles of vinorelbine, capecitabine, and gemcitabine combined were consistent with that of TPC overall and with eribulin. One treatment-related death was reported for the TPC arm (eribulin) and none with SG. Conclusions: The efficacy benefit observed with SG vs TPC in pts with mTNBC was retained when evaluating each TPC chemotherapy agent individually. These results confirm that SG should be considered as a new standard of care in pts with pretreated mTNBC. Clinical trial information: NCT02574455 .

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Absolute Lymphocyte Count, Platelet-to-Lymphocyte Ratio, and Overall Survival in Eribulin-treated HER2-negative Metastatic Breast Cancer Patients

Cancer Diagnosis & Prognosis ◽

10.21873/cdp.10058 ◽

2021 ◽

Vol 1 (5) ◽

pp. 435-441

Author(s):

YOICHI KOYAMA ◽

SAORI KAWAI ◽

NATSUKI UENAKA ◽

MIKI OKAZAKI ◽

MARIKO ASAOKA ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Lymphocyte Count ◽

Univariate Analysis ◽

Metastatic Breast ◽

Absolute Lymphocyte Count ◽

Breast Cancer Patients ◽

Platelet To Lymphocyte Ratio ◽

Lymphocyte Ratio

Background/Aim: To investigate the utility of peripheral blood biomarkers – absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) – for predicting outcomes in eribulin-treated patients with metastatic human epidermal growth factor receptor type 2 (HER2)-negative breast cancer. Patients and Methods: ALC, NLR, and PLR were retrospectively obtained from pre-treatment blood sampling results of 120 patients and stratified according to means. Univariate and multivariate analyses were performed to investigate the association of clinicopathological factors, including these values, with overall survival (OS) and progression-free survival (PFS). Results: The ALC, NLR, and PLR cut-off points were 1,285/μl, 3.3, and 235, respectively. No biomarkers were associated with PFS. However, univariate analysis showed ALC (p=0.044) and PLR (p=0.044) to be significantly associated with OS. Conclusion: ALC and PLR can predict eribulin efficacy in terms of OS, reflecting the antitumour immune response in the microenvironment and indicating eribulin’s effectiveness.

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