Earlier use of ciltacabtagene autoleucel (cilta-cel) is associated with better immune fitness and stronger immune effects as shown by correlative analysis of peripheral blood and the bone marrow tumor microenvironment (TME) from the CARTITUDE-4 study. Utilizing data from the CARTITUDE-1 and -4 studies, researchers assessed the association between peripheral blood and bone marrow tumor microenvironment (TME) biomarkers and progression-free survival (PFS) and number of prior lines of therapy (pLOT) in patients with relapsed/refractory multiple myeloma (RRMM) treated with ciltacabtagene-autoleucel (cilta-cel). A total of 273 patients (CARTITUIDE-1, n=97; CARTITUDE-4, n=176) received cilta-cel as study treatment, and 248 (1 pLOT, n=56; 2 pLOT, n=61; ≥3 pLOT, n=131) had immunophenotyping data available. At apheresis, patients with 1 or 2 pLOT had a greater percentage of CD4+ naïve T cells compared to patients with ≥3 pLOT, and greater baseline levels of these cells were associated with longer PFS. Gene expression analysis was performed on 148 BMA samples (screening, n=50; Day 28, n=50; 6 months, n=48) from CARTITUDE-4, and results indicated the B cells and antibodies were depleted at Day 28 but partially recovered at 6 months. At Day 28, myeloid cell– and cytotoxic T cell–related gene expression was elevated. Genes associated with B-cell receptors, T-cell differentiation, and cytokine signaling pathways were found to be elevated at Day 28 and 6 months. In patients with PFS >18 months, levels of M1 tumor-associated macrophages were increased at Day 28; similarly, patients with 1 pLOT had greater elevation of M1 expression from screening to Day 28 compared to patients with 3 pLOT. At 6 months, patients with shorter PFS showed greater expression of regulatory T cells and more suppressed interferon pathway genes. Gene expression data indicated that patients with fewer pLOT had greater depletion of B cells at Day 28, improved recovery at 6 months, and increased B-cell receptor signaling. These data indicate that better baseline immune fitness, observed with 1 or 2 pLOT, and stronger immune fitness postinfusion were associated with longer PFS in patients treated with cilta-cel; however, the impact of immune fitness on response might be limited beyond 3 pLOT.
Access abstract here: https://ashpublications.org/blood/article/146/Supplement%201/92/549696/Earlier-use-of-ciltacabtagene-autoleucel-cilta-cel
Outcomes of urgent inpatient chemotherapy for relapsed/refractory multiple myeloma in the modern era. In this retrospective study, researchers evaluated outcomes of urgent, unplanned inpatient chemotherapy in patients with RRMM. Eighty-two patients who received unplanned inpatient chemotherapy from January 2021 to October 2023 were included for analysis. Median age at admission was 61.5 years; 56% of patients were female and 72% were White. Fifty-two percent of patients had an Eastern Cooperative Oncology performance status (ECOG PS) ≥2. Median number of pLOT was 4. Two-thirds of patients experienced disease refractoriness to last LOT, and 44% had relapsed following autologous stem cell transplant (ASCT). Over half of patients had hypoalbuminemia (87%), thrombocytopenia (57%), and elevated lactate dehydrogenase (LDH; 52%). Additionally, 48% of patients had renal dysfunction (glomerular filtration rate [GFR] <45 mL/min/1.73m2). Median (range) hospital stay was 10 (2–89) days. Twenty-nine percent of patients required intensive care unit (ICU) stay for a median (range) length of 6 (2–83) days. Dialysis, use of vasopressors, and mechanical ventilation were required in 21%, 20%, and 13% of patients, respectively. Most patients (68%) were discharged home. Progressive disease (PD) occurred in 24 patients; 21 achieved partial response, 8 achieved very good partial response, and 2 achieved complete response. After admission, 21% of patients received chimeric antigen receptor T-cell (CAR T) therapy, and 22% received bispecific antibody treatment. At the time of analysis, 88% of patients had died, and 10% were alive without PD. Median PFS and overall survival (OS) were 1.5 and 4.9 months, respectively. The 3-month PFS rate was 38% (95% confidence interval [CI]: 28–50%), and 3-month OS rate was 68% (95% CI: 59–79%). Univariate analysis showed that being refractory to last LOT and ICU admission were associated with worse OS (P=0.0035 and 0.0012, respectively) and PFS (P=0.0363 and 0.0156, respectively), while discharge home was associated with improved OS (P=0.0021) and PFS (P=0.0344). Furthermore, elevated LDH and low GFR (≤40-60 mL/min/1.73m2) were associated with inferior OS (P=0.0384 and 0.0234, respectively). Treatment with CAR T therapy or bispecific antibodies was associated with improved OS.
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Racial disparities in clinical outcomes among patients with newly diagnosed and relapsed multiple myeloma in the United States: a 21-year comparative analysis. Researchers assessed racial disparities in adverse clinical outcomes and survival among patients with MM. Data spanning 2000 to 2020 from the TriNetX United States Collaborative Network were analyzed. Compared to White patients with newly diagnosed MM (NDMM), Black patients had significantly increased risk of stroke, chronic kidney disease (CKD), seizures, and heart failure, with relative risks (RRs) (95% CIs) of 1.45 (1.24–1.61), 1.41 (1.30–1.50), 1.34 (1.18–1.53), and 1.25 (1.17–1.34), respectively, as well as a lower risk of osteoporosis (RR: 0.64; 95% CI: 0.59–0.71). The risk of all-cause mortality was decreased in Black vs White patients with NDMM (RR: 0.94; 95% CI: 0.90–0.98). Findings were similar in the RRMM group; risk of CKD (RR: 1.45; 95% CI: 1.27–1.65), stroke (RR: 1.41; 95% CI: 1.05–1.90), seizures (RR: 1.39; 95% CI: 1.07–1.83), and heart failure (RR: 1.34; 95% CI: 1.17–1.53) were increased and all-cause mortality (RR: 0.91; 95% CI: 0.85–0.98) was lower in Black patients compared to White patients. In the NDMM group, rates of hospitalization (RR: 0.90; 95% CI: 0.81–0.99), osteoporosis (RR: 0.72; 95% CI: 0.59–0.89), and seizure (RR: 0.64; 95% CI: 0.44–0.94) were significantly lower in Asian patients compared to White patients. Mortality did not significantly differ between Asian and White patients with NDMM. Adverse clinical outcomes were not significantly different between Asian and White patients in the RRMM group, but Asian patients showed significantly lower morality, with a RR (95% CI) of 0.81 (0.67–0.99).
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Factors associated with remote healthcare utilization in MM patients undergoing autologous stem cell transplantation. In this retrospective analysis, researchers evaluated the frequency of remote unscheduled healthcare interactions (rUHIs) and aimed to identify predictive factors of remote healthcare utilization among patients with MM undergoing high-dose melphalan followed by ASCT (HDM/ASCT). Data from April 1, 2022, to July 2, 2024, were included for analysis. RUHIs encompassed any unscheduled contact between the patient and physician’s office that did not involve an in-person visit or scheduled telehealth appointment (eg, electronic messages via patient portals, telephone calls). Among 100 patients with a median age of 63 years, 88% received HDM/ASCT as first-line treatment and 28% received ASCT in an outpatient setting. Patients had a median of 4 rUHIs (range: 0–20), with the most frequent topics being patient education (19%), care logistics (17%), symptoms of infection (12%), dermatologic symptoms (9%), and gastrointestinal symptoms (7%). Less than 9% of rUHIs led to in-person assessments. Pre-admission ECOG PS of 1 was associated with a 2.1-fold increase in rUHI compared to ECOG PS of 0 (P= 0.0001). Higher Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) score was linked to greater rUHI, with each 1-point increase associated with a 9.9% increase in rUHI (P=0.016). There was a 1.8-fold increase in rUHI among patients referred from outside the transplant center vs patients referred by in-center specialists (P=0.006). Inpatient receipt of HDM/ASCT was associated with a 2.1-fold increase in the number of rUHIs compared to outpatient receipt (P=5×10–5). Aside from HCT-CI, these factors maintained significance on multivariate analysis.
Access abstract here: https://ashpublications.org/blood/article/146/Supplement%201/2632/555998/Factors-associated-with-remote-healthcare