Tario, Joseph D.

7528 Background: Lenalidomide (Len) maintenance after ASCT has been a standard of care for patients (pts) with MM. Historically, ~30% of pts discontinue Len within 1 year (yr) due to toxicity and there is a need for more effective and better tolerated maintenance strategies. Iber is a potent, oral cereblon E3 ligase modulator under evaluation in the relapsed/refractory and newly diagnosed settings. We report the results of the primary analysis of a Phase II trial of Iber maintenance following upfront ASCT. Methods: Pts ≥ 19 yrs of age with MM, within 1-yr of initiation of induction therapy and in a ≥ partial response (PR) at day 80-110 post-ASCT, were accrued. Iber was administered 1.0 mg orally days 1-21 of a 28-day cycle, continued until progressive disease (PD) or toxicity. Up to 2 dose reductions (0.75 mg/day then 0.6 mg/day) were allowed. Growth factor support was not permitted. Minimal residual disease (MRD) assessment by flow cytometry (10 -5 ) was performed at registration, post-cycle 12 and post-cycle 24. An optimal Simon two-stage design with type I and II errors of 0.1 was chosen to test whether the proportion of pts who are progression-free and on treatment at 1 yr is <60% against the alternative of ≥ 80%. If ≥ 27 out of 38 pts were progression-free (by 2016 IMWG criteria) and on treatment at 1 yr, Iber would be considered to have promising activity. Results: 38 pts (55% males, median age 61 yrs (range: 41-77)) received Iber. R-ISS at diagnosis was stage I (34%), II (39%), III (8%) and unknown (18%), with 34% having high-risk disease per 2025 IMS/IMWG criteria. All pts received triplet or quadruplet induction therapy, with 97% receiving Len and 84% receiving daratumumab. At day 80-110 post-ASCT, all pts had ≥ very good PR, with 22 (58%) ≥ complete response (CR) and 33 (87%) MRD-negative (neg). The median number of administered treatment cycles is 18 (range: 1-45), with 18 (47%) pts having ≥ 1 dose reduction, most commonly due to neutropenia (n=12). The most common grade (gr) 3/4 adverse event was neutropenia (gr 3 (n=19), gr 4 (n=5)). Within yr 1, 29% (11/38) discontinued Iber due to neutropenia (n=5), rash (n=1), infection (n=1), pt choice (n=1), or PD (n=3). After 1 yr, 6 pts discontinued due to neutropenia (n=4) and PD (n=2). While on Iber, 19 pts had deepening of response to stringent CR and 3 pts converted from MRD-positive to MRD-neg. The post-cycle 12 and 24 MRD-neg rates are 85% (23/27) and 100% (14/14), respectively. Conclusions: Iber demonstrated promising activity with dose reductions/discontinuations mainly due to neutropenia. Strategies including lower starting dose, growth factor support and more flexible management of neutropenia may enable more pts to remain on treatment. Longer follow-up will permit evaluation of sustained MRD-negativity and PFS, but overall, these results provide rationale for further exploration of Iber-based post-ASCT maintenance strategies. Clinical trial information: NCT05177536 .

AbstractProblemPrevious studies identified circulating CD14+HLA‐DRlo/− monocytic cells as an immune suppressive subset in solid malignancies, such as prostate, renal cell carcinoma, and pancreatic cancer. Such monocytic cells have been implicated not only in tumour progression but also as a potential barrier for immunotherapy. This study examined the relationship between the frequency of circulating monocytic cells and epithelial ovarian cancer (EOC) progression pre‐ and post‐frontline chemotherapy, defined by disease stage, which is a leading prognostic factor for this malignancy.Method of studyIncident cases of 236 women with EOC were recruited and comprehensive flow cytometry was utilized to assess the frequency of peripheral blood CD33+CD11b+HLA‐DR−/lowCD14+CD15− monocytic cells, henceforth termed CD14+HLA‐DRlo/− monocytic cells, prior to and after completion of frontline chemotherapy. Multivariable odds ratios (OR) were used to estimate the association between CD14+HLA‐DRlo/− monocytic cell percentages and disease stage. Wilcoxon signed‐rank tests evaluated changes in these monocytic cell levels pre‐ and post‐chemotherapy in a patient subset (n = 70).ResultsPatients with elevated frequencies of circulating CD14+HLA‐DRlo/− monocytic cells at diagnosis were at 3.33‐fold greater odds of having advanced stage (III/IV) EOC (CI: 1.04‐10.64), with a significant trend in increasing CD14+HLA‐DRlo/−monocytic cell levels (P = .04). There was a 2.02% median decrease of these monocytic cells post‐chemotherapy among a subset of patients with advanced stage disease (P < .0001).ConclusionThese findings support the potential clinical relevance of CD14+HLA‐DRlo/−monocytic cells in EOC for prognosis and may indicate a non‐invasive biomarker to measure disease progression.