Citations

8012 Background: Cilta-cel was FDA approved in 2022 for the treatment of RRMM. We evaluated the outcomes of patients treated with intended SOC cilta-cel. Methods: 12 US academic medical centers contributed data to this retrospective study. As of 12/31/2022, 177 patients were leukapheresed and 139 received cilta-cel. Results: The table describes the study population compared to the CARTITUDE-1 trial. More patients in our study had extramedullary disease (EMD, 35%) and high-risk cytogenetics (41%). 55% of the patients would not have met eligibility criteria for CARTITUDE-1. Common reasons for ineligibility were cytopenias (19%), prior BCMA therapy (14%), organ dysfunction (12%), oligosecretory disease (13%), and plasma cell leukemia (8%). 83% of the patients received bridging chemotherapy (overall response rate, ORR: 28%). Lymphodepletion included fludarabine (Flu) + cyclophosphamide (Cy): 81%, bendamustine: 11%, Cy: 4%, and cladribine + Cy: 4%. Median CAR-T cells infused were 0.6 million/kg (range: 0.1-0.9), and 19% of patients were treated on an expanded access protocol (EAP). Median follow-up was 2.3 months (range: 0-8). Cytokine release syndrome (CRS) was seen in 81% (≥ grade 3: 7%) and immune effector cell-associated neurotoxicity syndrome (ICANS) in 22% (≥ grade 3: 8%) of patients. Tocilizumab, steroids, and anakinra were used in 61%, 44%, and 10% of patients, respectively. Delayed neurotoxicity (NT) was seen in 9% (cranial nerve palsy: 8, Parkinsonism: 2, others: 3). Grade ≥ 3 cytopenias at day ≥ 30 were seen in 75% of patients. Infections were seen in 32% of patients. Day 30 (N=115) and best response rates (N=118) were: ≥ partial response (PR), 75/80%; ≥ very good PR, 44/62%; and ≥ complete response (CR), 26/40%, respectively. In the non-EAP FluCy population (N=88), best ORR/≥CR were 89/49%. 17 patients died by data cut-off, 4 due to disease progression and 13 (9%) due to non-relapse mortality (NRM) (grade 5 CRS: 3, infection: 6, CRS/infection: 1, grade 5 ICANS: 1, delayed NT: 2). Conclusions: Patients treated with intended SOC cilta-cel had a favorable ORR (80%) despite a larger proportion of patients having high-risk features relative to trial patients and limited follow-up. Response rates were higher in patients receiving conforming products with FluCy conditioning (89%). Delayed NT and NRM were seen in 9% of patients. Results will be updated with continued follow-up. D.K.H., K.K.P, M.J., Y.L. & S.S. contributed equally. [Table: see text]

LBA7564 Background: Patients with r/r B-NHL have a dismal prognosis. DIAL (Dual Immunomodulation in Aggressive Lymphoma) was a multi-center randomized phase II study testing the efficacy of nivolumab (PD-1 inhibitor) plus varlilumab (CD27 agonist) in this population. Methods: Patients were randomized (1:1) to nivolumab (240 mg IV every 2 weeks for 4 months, 480 mg IV monthly thereafter; group 1) alone or combined with varlilumab (3 mg/kg IV monthly; group 2). Cross-over (group 1 to 2) was allowed for progression. Primary endpoint was overall response (ORR) per LYRIC criteria. A sample size of 48 patients per arm would provide 80% power to detect increase in ORR from 25% to 45% using a one-sided test (p = 0.15). Pre-specified interim analysis occurred after half of the patients completed first radiologic assessment. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Exploratory endpoints included tumor genomic assessment and immune profiling of blood and tumor. Results: 53 patients were enrolled (27 in group 1; 26 in group 2). Interim analysis included 24 patients from each arm. Mean age was 65.2 years, 34 (70.8%) were male, and 36 (75%) received prior CAR-T cell therapy. Baseline characteristics were balanced between arms. Grade ≥ 3 AEs were observed in 8 (33.3%) and 7 (30.4%) of patients in groups 1 and 2, respectively. Common AEs (> 5%) of any grade included fatigue, lymphopenia, diarrhea, rash. There were no treatment-associated deaths. Toxicity profile was similar between arms. Table summarizes efficacy outcomes. ORR was achieved in 6 patients (12.5%), not statistically different between arms; 4 responses were complete. Seven patients crossed over (1 responded after crossing). Median OS (8.6 vs 7.3 months; p = 0.39) and PFS (2.7 vs 1.4 months; p = 0.06) were similar between arms. Subgroup analysis of patients with prior CAR-T cell therapy showed similar ORR (5/36; 14%), not statistically different between arms. Correlative analysis results will be presented at conference. The trial met futility criterion on interim analysis and enrollment ceased based on pre-specified stopping rule. Conclusions: Dual immunomodulatory therapy did not enhance anti-tumor activity in patients with aggressive B-NHL compared to nivolumab alone. Response rates were low and consistent with previous data using PD-1 inhibitors in this population. Prior therapy with CAR-T cell does not seem to sensitize patients to PD-1 blockade. Toxicity profile was acceptable and dual therapy did not increase the rate of AEs. Clinical trial information: NCT03038672. [Table: see text]

PURPOSE Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested that CNI-free approaches using donor T-cell depletion, either by ex vivo CD34 selection or in vivo post-transplant cyclophosphamide (PTCy) as a single agent, are associated with lower rates of chronic GVHD (cGVHD). METHODS This multicenter phase III trial randomly assigned patients with acute leukemia or myelodysplasia and an HLA-matched donor to receive CD34-selected peripheral blood stem cell, PTCy after a bone marrow (BM) graft, or tacrolimus and methotrexate after BM graft (control). The primary end point was cGVHD (moderate or severe) or relapse-free survival (CRFS). RESULTS Among 346 patients enrolled, 327 received HCT, 300 per protocol. Intent-to-treat rates of 2-year CRFS were 50.6% for CD34 selection (hazard ratio [HR] compared with control, 0.80; 95% CI, 0.56 to 1.15; P = .24), 48.1% for PTCy (HR, 0.86; 0.61 to 1.23; P = .41), and 41.0% for control. Corresponding rates of overall survival were 60.1% (HR, 1.74; 1.09 to 2.80; P = .02), 76.2% (HR, 1.02; 0.60 to 1.72; P = .95), and 76.1%. CD34 selection was associated with lower moderate to severe cGVHD (HR, 0.25; 0.12 to 0.52; P = .02) but higher transplant-related mortality (HR, 2.76; 1.26 to 6.06; P = .01). PTCy was associated with comparable cGVHD and survival outcomes to control, and a trend toward lower disease relapse (HR, 0.52; 0.28 to 0.96; P = .037). CONCLUSION CNI-free interventions as performed herein did not result in superior CRFS compared with tacrolimus and methotrexate with BM. Lower rates of moderate and severe cGVHD did not translate into improved survival.