ALBERT

Description: There is a continued unmet medical need in pts with relapsed/refractory Hodgkin's lymphoma (RR HL). Curing HL pts who have refractory disease after salvage chemotherapy, who relapse after ASCT, or those who are not candidates for ASCT, remains a clinical challenge due to limited effective treatments. There are data available indicating that brentuximab vedotin (BV) brings considerable promise for the treatment of pts with RR HL. Information about BV treatment effectiveness and tolerability both from physician's and patient's perspective is worthwhile in this difficult patient population. We aimed to evaluate clinical and patient-reported outcomes in RR HL patients receiving BV as 〉2nd treatment line. Here we report the outcomes with respect to clinical response, tolerability, quality of life (QoL) and symptoms after 3 mos of BV treatment. The total number of pts to be included in the multicenter observational real-world study is 70 pts with RR HL who received BV 1.8 mg/kg q3w till disease progression, intolerance toxicity of BV or refusal. Treatment response was assessed using RECIST criteria v. 1.0. Adverse events (AEs) were assessed in accordance with NCI CTCAE v. 4.03. For QoL assessment pts filled out RAND SF-36, for symptom assessment - ESAS questionnaire; also pts filled out PGIC scale for self-assessment of changes in their health. For QoL analysis paired t-test, Mann-Whitney test, Wilcoxon test and χ2 were used. The analysis was performed in the group of 55 pts RR HL (median age - 28 years, range 18-67, 54.5% males) who were involved in the study: 63.6% pts had advanced stage (III-IV) at diagnosis; ≥50% pts had B-symptoms (58.2%); 82% pts - ECOG 0-1. All the pts received a median of 3 previous treatment lines; among them 14 pts (25.5%) failed to ASCT in the past; half of pts were primary chemotherapy resistant (49%). Before BV treatment start QoL was dramatically worsened for all SF-36 scales (p70% pts) symptoms were drowsiness, tiredness, anxiety, and worse wellbeing. More than half pts had moderate-to-severe drowsiness,tiredness, depression, lack of appetite and worsened wellbeing before BV treatment start. After 3 mos of BV treatment objective response was registered in 55% pts with 27.5% complete response. Adverse events of grade I-II were reported in 8 pts (20%) and were consistent with known toxicities. Most common adverse events (≥10%) were increasing ALT and AST (each 4/8), peripheral neuropathy, fatigue, skin itch (each 3/8). Severe adverse event (III grade) not related with BV occurred in one patient (2.5%) - sepsis, respiratory insufficiency due to agranulocytosis (BV was temporary stopped). During BV treatment meaningful QoL improvement was revealed for all SF-36 scales (p

Description: Abstract 4825 Wilms' tumor gene 1 (WT1) that encodes a transcription factor has elevated expression in 90% of AML. High level of WT1 gene expression in bone marrow and peripheral blood of patients with AML indicates the presence of leukemia tumor burden. Thus, quantifying assessment of the level of WT1 could predict relapse. It is important to monitor a universal marker in the absence of target molecular genetic abnormalities in the disease onset. There are few data related to extramedullary relapses. Here we describe the patient with extramedullary relapse without concomitant elevation of WT1 expression. The patient is 22 year old male with the first early bone marrow and CNS relapse of AML. Cytogenetics- (45XY, t (3, 5) (q29; q15), −7, der (7), add (11) (p15)). Blast cells immunophenotype was CD45 + CD34 + CD38 + CD117 +. There was high blast count with high expression of WT1 level (Tabl 1). And there was no expression of other molecular genetic prognostic markers. Therapy with high dose of cytarabine with intrathecal administration of cytotoxic drugs was conducted. The complete hematological and cytogenetic remission was achieved after the first induction. Also there was no any blast cell in the CSF, WT1 expression decreased by 1,87 log (WT1 level became normal). Consolidation of remission with three similar courses with high doses of cytarabine was conducted. Extramedullary relapse during bone marrow and CNS remission with unilateral lesion of the lacrimal gland and the periorbital area( 2.8 × 3.4×4.6 cm )was diagnosed in 6 month. Relapse was confirmed by histological and immunochemical study of the left lacrimal gland biopsy, blasts phenotype was similar to the phenotype of bone marrow blasts at AML onset. WT1 level in bone marrow and peripheral blood remained within normal limits: 15.5 WT1/104 ABL copies and 13.4 WT1/104 ABL copies respectively. Therapy with high dose cytarabine and mitoxantrone was used as an induction. After this therapy a local remission was diagnosed according to MRI. Consolidation courses were followed by a course of radiotherapy to the area of the left orbit. Bone marrow remission and low-level expression of WT1 remained to be normal. Thereafter the patient has undergone unrelated allogeneic bone marrow transplantation. Conclusion. We have described isolated AML relapse without elevation of WT1. A possible reason for normal level of expression of WT1 in patients with extramedullary relapse may be a small amount of the extramedullary formation, its location and features of blood supply of the body area. Disclosures: No relevant conflicts of interest to declare.

Description: Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. Adults age ≥18 years with newly diagnosed AML ineligible for intensive chemotherapy were enrolled in this international phase 3 randomized double-blind placebo-controlled trial. Patients (N = 211) were randomized 2:1 to venetoclax (n = 143) or placebo (n = 68) in 28-day cycles, plus low-dose cytarabine (LDAC) on days 1 to 10. Primary end point was overall survival (OS); secondary end points included response rate, transfusion independence, and event-free survival. Median age was 76 years (range, 36-93 years), 38% had secondary AML, and 20% had received prior hypomethylating agent treatment. Planned primary analysis showed a 25% reduction in risk of death with venetoclax plus LDAC vs LDAC alone (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.52-1.07; P = .11), although not statistically significant; median OS was 7.2 vs 4.1 months, respectively. Unplanned analysis with additional 6-month follow-up demonstrated median OS of 8.4 months for the venetoclax arm (HR, 0.70; 95% CI, 0.50-0.98; P = .04). Complete remission (CR) plus CR with incomplete blood count recovery rates were 48% and 13% for venetoclax plus LDAC and LDAC alone, respectively. Key grade ≥3 adverse events (venetoclax vs LDAC alone) were febrile neutropenia (32% vs 29%), neutropenia (47% vs 16%), and thrombocytopenia (45% vs 37%). Venetoclax plus LDAC demonstrates clinically meaningful improvement in remission rate and OS vs LDAC alone, with a manageable safety profile. Results confirm venetoclax plus LDAC as an important frontline treatment for AML patients unfit for intensive chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03069352.

Description: Background : For patients (pts) with acute myeloid leukemia (AML), preserving and measuring perceptions of health-related quality of life (HRQoL) is important, particularly for those ineligible for intensive chemotherapy and with a poor prognosis, especially when evaluating new treatment regimens. This analysis from 2 Phase 3 trials, Viale-A (NCT02993523) and Viale-C (NCT03069352), evaluated HRQoL, including key symptoms and aspects of functioning, in pts with AML receiving venetoclax (VEN) co-administered with azacitidine (AZA) (Viale-A) or low-dose cytarabine (LDAC) (Viale-C). Methods: Viale-A and Viale-C included treatment-naïve pts with AML, ≥18 years of age, and ineligible to receive intensive chemotherapy. Pts were randomized 2:1 to receive VEN +AZA or placebo (PBO)+AZA in Viale-A, and VEN+ LDAC or PBO+LDAC in Viale-C. Pt-reported outcome (PRO) measures included the PROMIS Cancer Fatigue Short Form 7a, the EORTC QLQ-C30 global health status (GHS)/QoL and physical functioning [PF] subscales, and the EQ-5D-5L health status visual analog scale (VAS). PRO data were collected on Day 1 of every 28-day cycle throughout both trials. Time to deterioration (TTD) was assessed to quantify differences between treatment groups. TTD was defined as worsening from baseline in PRO-specific meaningful change thresholds of ≥10, 7, or 5 points for the EORTC-QLQ-C30, EQ-5D-5L VAS, and PROMIS Fatigue, respectively. TTD differences between treatment arms were analyzed using Kaplan-Meier curves, unadjusted log-rank tests, and Cox PH models adjusted for key covariates (age, baseline ECOG and PRO scores, AML type, and cytogenetic risk category). TTD analyses were conducted for all pts in the full dataset who survived up to a given assessment with available data on ≥1 PRO measures from baseline. Results: Viale-A included 431 pts (VEN+AZA: 286, PBO+AZA: 145), of whom 60% were male; median age was 76 years. Compared with PBO+AZA pts, VEN+AZA pts had a non-statistically significant trend to longer TTD in GHS/QoL (median in months [95% CI]: 16.5 [95% CI: 9.8, NE] vs. 9.3 [95% CI: 4.7, 16.6], P=0.066) and fatigue (9.3 [7.2, 16.6] vs. 8.6 [4.2, 16.6], P=0.189) (Figure 1A, B). VEN+AZA pts had significantly longer TTD in PF (9.7 [6.7, 16.0] vs. 6.2 [4.7, 9.5], P=0.028) and health status VAS (10.7 [7.5, 18.6] vs. 3.9 [2.4, 7.4], P