Emechebe, Nnadozie

Abstract Background: Venetoclax (VEN)+obinutuzumab (VO) is an effective therapy for CLL/SLL requiring regular monitoring for tumor lysis syndrome (TLS) during VEN ramp-up. The CLL14 trial of VO reported no TLS during VEN ramp-up; however, there are limited real-world data on monitoring practices and TLS outcomes for different dose levels and monitoring timepoints. This study assessed VEN initiation prophylaxis and monitoring outcomes for patients (pts) with CLL/SLL starting VO in first line (1L) in an outpatient, real-world setting. Methods This interim analysis relied onretrospective observational data from 4 US sites of the CLL Collaborative Study of Real-World Evidence (CORE). Adult pts with CLL/SLL were eligible if they: (1) started VO per-label outside of a clinical trial in 1L, or immediately after exposure in 1L to agents with different mechanisms of action (i.e., BTKi, anti-CD20 only) of <30 days; (2) prior to VEN start, had either (i) low physician-determined tumor burden (TB) (i.e., all lymph nodes [LN] <5 cm and ALC <25 x 109/L), or (ii) medium physician-determined TB (i.e., any LN ≥5-<10 cm or ALC ≥25 x 109/L) with creatinine clearance ≥80 mL/min; (3) had no strong CYP3A inhibitors or prophylactic rasburicase from 3 days prior to VEN start until end of VEN ramp-up; and (4) had VEN ramp-up in an outpatient setting. TB-related labs/imaging was assessed from 2 months prior to obinutuzumab initiation (i.e., index date) until VEN start. VEN characteristics (i.e., dosing, duration), prophylaxis measures (i.e., antihyperuricemics and IV hydration), and TLS-related monitoring and management (i.e., lab results and interventions received) were collected per ramp-up week and TLS monitoring timepoint. Results Of 128 pts in CORE who initiated VO in any line, 72 pts met inclusion criteria (low TB: 57 [79.2%]; medium TB: 15 [20.8%]). Median (IQR) age was 62 (56.0, 68.5) years, 58.3% were male, and 81.9% had ECOG grade ≤1. Among pts tested, 7/68 (10.3%) had del(17p)/TP53 mutation and 43/66 (65.2%) had unmutated IGHV. Median (IQR) time from index to VEN start was 23.0 (22.0, 30.0) days. Most pts completed ramp-up (98.6% [71/72]) and followed a per-label regular dosing schedule (93.1% [67/72]). Prior to VEN ramp-up, all pts received prophylactic antihyperuricemics (allopurinol: 71 [98.6%]; febuxostat: 2 [2.8%]) and prophylactic hydration. In the 2 days prior to a dose escalation for at least 1 week of ramp-up, prophylactic IV hydration was reported for 27 (37.5%) pts based on physician determination. One pt stopped VEN after week 2 due to neutropenia (grade 3+). During ramp-up (median [IQR] of 9 [8, 12] blood tests per pt), no lab or clinical TLS was reported. Of 21 (29.2%) pts who received an intervention following a lab assessment, most had low TB at VEN start (16 [76.2%]). All interventions were either prophylactic or non-TLS-related. Following a lab assessment for at least 1 week of ramp-up, prophylactic IV or escalated oral hydration intervention was reported in 17/21 pts (81.0%) based on physician determination (e.g., to manage impaired baseline renal function in those with low TB, patient request, or institutional practice) (IV hydration: 15 pts; escalated oral hydration: 2 pts). By per-label monitoring timepoints, hydration intervention was given prophylactically following pre-dose lab tests for 7 pts (across weeks 1-5), 6-8 hours post-dose for 5 pts (weeks 1-2), and 24 hours post-dose for 10 pts (weeks 1-2). By per-label monitoring timepoints, other non-TLS-related interventions (i.e., blood transfusion for anemia, insulin for hyperglycemia, and potassium for non-TLS-related hypokalemia) were given following pre-dose lab tests for 2 pts (weeks 1-5) and 24 hours post-dose for 4 pts (weeks 1-2). Conclusion Consistent with the CLL14 trial, no TLS was reported in this real-world, interim analysis of pts with mostly low TB and good renal function at 1L VO initation. All interventions during VEN ramp-up were prophylactic or non-TLS-related, with prophylactic hydration commonly given based on physician preference. These results suggest that VO initiation is manageable in an outpatient setting. Consideration should be given for simplified monitoring requirements including potential removal of 6-8 hour post-dose lab in this population and be further explored in prospective studies. Data collection for this study is ongoing to further contextualize real-world VEN initiation prophylaxis and monitoring outcomes in a larger cohort.

Abstract Background: Initial studies with venetoclax, a BCL-2 inhibitor, alone or in combination with either dexamethasone or bortezomib and dexamethasone has shown considerable anti-tumor activity in t(11;14) MM with relapsed disease. Based on preclinical studies suggesting synergy when combined with bortezomib and phase 1 data showing efficacy for venetoclax, this combination was compared with bortezomib and dexamethasone (BortDex) in relapsed MM. While the BELLINI (NCT02755597) trial did demonstrate improved PFS with the combination, there were limited number of patients with t(11;14) treated with BortDex. The objective of this study was to assess real-world effectiveness of BortDex in patients with t(11;14) positive relapsed/refractory MM. Patients and methods: This non-interventional, retrospective observational cohort study included patients with t(11;14) MM from the International Myeloma Working Group (IMWG) retrospective study of t(11;14) MM. From the overall cohort, patients with t(11;14) MM receiving BortDex in ≥2 nd and ≤4 th line were initially selected. The cohort was further limited to patients with no evidence of allogeneic SCT within 16 weeks or autologous SCT within 12 weeks prior to BortDex initiation. Finally, patients non-refractory to prior PI regimen and not receiving BortDex regimen as part of a clinical trial were included in the study. Patient demographic and clinical characteristics along with real-world effectiveness outcomes including best response, overall survival (OS), and time to next therapy (TTNT) as a surrogate measure for progression-free survival (PFS) were assessed. All analyses were descriptive in nature and were conducted using the SAS 9.4 (SAS Institute Inc., Cary, NC, USA). Results: Overall, 144 patients who met the inclusion criteria were analyzed. Median age was 62.5 years, 62% were male. Patients had a median of 1 prior line (range 1-3) at start of BortDex, at a median of 18.4 months (range, 1-100) from diagnosis; 29% had a prior transplant. A PR or better was observed in 53% of patients with BortDex. The median TTNT for this cohort was 8.4 months and median OS was 46.1 months. Conclusions: This retrospective study of non-trial patients with t(11;14) MM provides a benchmark for newer therapies in this patient population for comparison with both venetoclax dexamethasone as well as combinations using the -BortDex backbone. Disclosures Emechebe: AbbVie: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; Pharmaceutical/Biotech Companies: Current holder of stock options in a privately-held company. Kumar: Tenebio: Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Carsgen: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche-Genentech: Consultancy, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Beigene: Consultancy; Antengene: Consultancy, Honoraria; Bluebird Bio: Consultancy; Merck: Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; BMS: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Goldschmidt: Takeda: Consultancy, Research Funding; Novartis: Honoraria, Research Funding; Mundipharma: Research Funding; MSD: Research Funding; Molecular Partners: Research Funding; Dietmar-Hopp-Foundation: Other: Grant; Sanofi: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Janssen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Incyte: Research Funding; GSK: Honoraria; Chugai: Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; BMS: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Celgene: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Adaptive Biotechnology: Consultancy; Amgen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Johns Hopkins University: Other: Grant. Mateos: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria; Sea-Gen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene - Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bluebird bio: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; Oncopeptides: Honoraria. Kim: Janssen, BMS: Research Funding. Dimopoulos: Janssen: Honoraria; Takeda: Honoraria; Beigene: Honoraria; BMS: Honoraria; Amgen: Honoraria. Ludwig: Janssen, Celgene-BMS, Sanofi, Seattle Genetics: Consultancy, Speakers Bureau; Amgen, Takeda: Consultancy, Research Funding, Speakers Bureau. Handa: Kyowa Kirin: Research Funding; Chugai: Research Funding; Celgene: Honoraria, Research Funding; Daiichi Sankyo: Research Funding; Janssen: Honoraria; BMS: Honoraria; Ono: Honoraria; Sanofi: Honoraria, Research Funding; Abbvie: Honoraria; MSD: Research Funding; Shionogi: Research Funding; Takeda: Honoraria, Research Funding. Fernandez de Larrea: Janssen: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Honoraria, Research Funding; GSK: Honoraria; Sanofi: Consultancy. Reece: Amgen: Consultancy, Honoraria; GSK: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Honoraria; Millennium: Research Funding; Karyopharm: Consultancy, Research Funding; BMS: Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding. Raje: Celgene, Amgen, Bluebird Bio, Janssen, Caribou, and BMS: Other. Karve: AbbVie: Current Employment, Current equity holder in publicly-traded company. Arriola: AbbVie: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Ross: AbbVie: Current Employment, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company. Durie: Amgen: Other: fees from non-CME/CE services ; Amgen, Celgene/Bristol-Myers Squibb, Janssen, and Takeda: Consultancy.

Abstract Complicated grief (CG), severe, prolonged (>12 months) grieving, disproportionately affects older adults. A prospective two-group, waitlisted RCT examined whether four sessions of Accelerated Resolution Therapy (ART) was effective in informal caregivers by comparing pre-to-post ART changes and investigating variation in treatment response by baseline CG levels. Inclusion: ≥60 years, Inventory of Complicated Grief >25. Paired t-tests of mean (SD) differences compared pre- to post-ART; pre-ART to 8-week follow-up, and post-ART to 8-week follow-up; then stratified by median baseline level of CG. Mean (SD) age of 54 participants was 68.7 (7.2) years, 85% female, and 93% white. Significantly greater CG reduction (-22.8 (10.3)) vs. waitlist (-4.3 (6.0)) was found. Within-participant effect sizes from baseline to 8-weeks post treatment were 1.96 (95% CI: 1.45, 2.47; p<0.0001). Treatment effects did not substantially differ by baseline levels. Lesson learned was that it was possible to successfully recruit and treat CG in the community.

Background and Objectives: Complicated grief (CG) is severe, prolonged (>12 months) grieving. Complicated grief disproportionately affects older adults and is associated with negative physical/psychological effects. Although treatment options exist, those which do are time-intensive. We report on a randomized clinical trial (RCT) which examined whether accelerated resolution therapy (ART), a novel mind-body therapy, is effective in treating CG, post-traumatic stress disorder (PTSD), and depression among hospice informal caregivers. Research Design and Methods: Prospective 2 group, wait-listed RCT. All participants were scheduled to receive 4 ART sessions. Inclusion: ≥60 years, inventory of CG >25, and PTSD checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition >33 or Psychiatric Diagnostic Screen Questionnaire PTSD subscale >5. Exclusion: Major psychiatric disorder, other current psychotherapy treatment. Depression was measured by the Center for Epidemiologic Studies Depression. Results: Mean (standard deviation [SD]) age of 54 participants was 68.7 (7.2) years, 85% female, and 93% white. Participants assigned to ART reported significantly greater mean (SD) CG reduction (−22.8 [10.3]) versus Wait-list participants (−4.3 [6.0]). Within-participant effect sizes (ESs) for change from baseline to 8-week post-treatment were CG (ES = 1.96 (95% confidence interval [CI]: 1.45-2.47; P < .0001), PTSD (ES = 2.40 [95% CI: 1.79-3.00]; P < .0001), depression (ES = 1.63 [95% CI: 1.18-2.08; P < .0001). Treatment effects did not substantially differ by baseline symptom levels. Discussion and Implications: Results suggests that ART presents an effective and less time-intensive intervention for CG in older adults. However, it should undergo further effectiveness testing in a larger, more diverse clinical trial with a focus on determining physiological or behavioral mechanisms of action.