The introduction of CD38-targeting monoclonal antibodies (CD38 MoABs), daratumumab and isatuximab, has significantly impacted the management of patients with multiple myeloma (MM). Outcomes of ...patients with MM refractory to CD38 MoABs have not been described. We analyzed outcomes of 275 MM patients at 14 academic centers with disease refractory to CD38 MoABs. Median interval between MM diagnosis and refractoriness to CD38 MoAB (T
) was 50.1 months. The median overall survival (OS) from T
for the entire cohort was 8.6 95% C.I. 7.5-9.9 months, ranging from 11.2 months for patients not simultaneously refractory to an immunomodulatory (IMiD) agent and a proteasome inhibitor (PI) to 5.6 months for "penta-refractory" patients (refractory to CD38 MoAB, 2 PIs and 2 IMiDs). At least one subsequent treatment regimen was employed after T
in 249 (90%) patients. Overall response rate to first regimen after T
was 31% with median progression-free survival (PFS) and OS of 3.4 and 9.3 months, respectively. PFS was best achieved with combinations of carfilzomib and alkylator (median 5.7 months), and daratumumab and IMiD (median 4.5 months). Patients with MM refractory to CD38 MoAB have poor prognosis and this study provides benchmark for new therapies to be tested in this population.
Objectives
Among advanced multiple myeloma (MM) patients, B-cell maturation antigen (BCMA) specific targets like Belantamab Mafodotin (belamaf) and CAR T-cell therapies have been shown to improve ...clinical outcomes, but at significant costs. To compare the expected costs per quality-adjusted life years (QALYs) gained among a hypothetical cohort of triple refractory MM patients treated with one of three BCMA-directed therapies: (1) idecabtagene vicleucel (ide-cel), (2) ciltacabtagene autoleucel (cilta-cel), and (3) belamaf for up to 20 months.
Methods
In this cost-effectiveness analysis, we built a Monte Carlo Markov Chain microsimulation model using estimates and parameters from the evidence on MM treatment for 10 000 hypothetical patients between the ages for 40 and 80. We assigned expected years of life remaining and made varying assumptions about survival beyond 5 years
Results
We predicted total cost of treatment for CAR-T therapy to be six times greater than for belamaf, but the QALYs gained from treatment are 6 to 8 times greater. Ide-cel was weakly dominated by cilta-cel and our base-case incremental cost effectiveness ratio (ICER) comparing cilta-cel with belamaf was $109,497 per QALY gained, averaging $123,618 in probabilistic sensitivity analyses.
Conclusions
These findings hinge on the assumption of longer-term survival but suggest that the use of CAR-T therapy is approaching standard ICER thresholds.
Chimeric Antigen Receptor T-cell (CAR-T) therapy has revolutionized the field of hematologic malignancies and are potentially curative in patients with previously limited options. This review ...highlights key abstracts focusing on clinical studies in CAR-T therapy in leukemia and lymphoma presented at the 61 st annual meeting of the American Society of Hematology (December 2019, Orlando, FL). Selected studies discuss data on novel CAR-T constructs aimed at enhancing efficacy and durability of responses, improving toxicity mitigation strategies, challenging clinical scenarios in routine clinical practice for standard of care CAR-T therapy (role of bridging therapy, CNS involvement, and quality of life studies), and new technologies aiming to decrease production time to minimize delay in definitive therapy, all within the rapidly-evolving cellular immunotherapy landscape.
Summary
In the relapsed/refractory setting for treatment of large B‐cell lymphoma (LBCL), chimeric antigen receptor T‐cell (CAR‐T) therapy has emerged as an effective treatment modality. Patients ...often have aggressive disease that requires prompt treatment in the form of bridging therapy (BT) for disease stabilisation while CAR‐T cells are manufactured. Patients (n = 75) undergoing CAR‐T therapy infusion for LBCL at our institution were identified. A total of 52 (69·3%) received BT and 23 (30·7%) received no BT (NBT). BT modalities included systemic BT (SBT) in 28 patients, radiation BT (RBT) in 14, and high‐dose steroid BT (HDS) in 10. There was no difference in incidence of cytokine release syndrome or immune effector cell‐associated neurotoxicity syndrome between BT and NBT (P = 0·18 and P = 0·53 respectively). Prolonged cytopenias at Day 180 were more common in BT than NBT (50% vs. 13·3%, P = 0·04). The SBT and RBT subgroups had more cytopenias at Day 180 compared to the HDS and NBT subgroups (58·3% and 57·1% vs. 20% and 13·3% respectively, P = 0·04). Disease response at last follow‐up, progression‐free survival and overall survival were similar between BT, NBT, and BT subgroups. In summary, BT can be safely considered in patients undergoing CAR‐T therapy. However, those undergoing BT with SBT or RBT are at higher risk of prolonged cytopenias after CAR‐T therapy.
Graphical schema of study: bridging therapy (BT), no BT (NBT), systemic BT (SBT), and high dose steroid BT (HDS) with reported 1‐year outcomes, cytokine release syndrome (CRS), immune effector cell‐associated neurotoxicity (ICANS), and day 180 cytopenias.
Previously undiagnosed anemia is often identified during routine assessment of surgical patients. Although studies suggest that perioperative anemia is associated with worse outcomes and a strong ...predictor for postoperative red cell transfusions, anemia is frequently ignored. Preoperative optimization of patients undergoing elective surgical procedures associated with significant blood loss, along with strategies to minimize intraoperative blood loss, shows promise for reducing postoperative transfusions and improving outcomes. In most situations, anemia can be corrected prior to elective surgeries and interventions. Future research should assess the timing and methods of optimization of preoperative anemia in surgery and which patients are best candidates for therapy.
Background
Persons newly diagnosed with pancreas cancer and who have survived a previous cancer are often excluded from clinical trials, despite limited evidence about their prognosis. We examined ...the association between previous cancer and overall survival.
Methods
This US population‐based cohort study included older adults (aged ≥66 years) diagnosed with pancreas cancer between 2005 and 2015 in the linked Surveillance, Epidemiology, and End Results‐Medicare data. We used Cox proportional hazards models to estimate stage‐specific effects of previous cancer on overall survival, adjusting for sociodemographic, treatment, and tumor characteristics.
Results
Of 32,783 patients, 18.7% were previously diagnosed with another cancer. The most common previous cancers included prostate (29.0%), breast (18.9%), or colorectal (9.7%) cancer. More than half of previous cancers (53.9%) were diagnosed 5 or more years prior to pancreas cancer diagnosis or at an in situ or localized stage (47.8%). The proportions of patients surviving 1, 3, and 5 years after pancreas cancer were nearly identical for those with and without previous cancer. Median survival in months was as follows for those with and without previous cancer respectively: 7 versus 8 (Stage 0/I), 10 versus 10 (Stage II), 7 versus 7 (Stage III), and 3 versus 2 (Stage IV). Cox models indicated that patients with previous cancer had very similar or statistically equivalent survival to those with no previous cancer.
Conclusions
Given nearly equivalent survival compared to those without previous cancer, cancer survivors newly diagnosed with pancreas cancer should be considered for inclusion in pancreas cancer clinical trials.
In this population‐based cohort of 32,783 patients diagnosed with pancreas cancer, nearly one in five were previously diagnosed with another cancer; commonly prostate, breast, or colorectal. Survival was nearly equivalent among those with and without previous cancer.
•LILRB4 is an immunoreceptor expressed on hematopoietic–lineage cells.•LILRB4 in animal models was demonstrated to orchestrate infiltration into the CNS.•LILRB4 was measured in human AML patients and ...they were followed for CNS disease.•LILRB4 was associated with the subsequent development of CNS involvement.•LILRB4 offers insight in the pathogenesis of AML seeding the CNS and novel therapies.
Central nervous system (CNS) involvement in patients with acute myeloid leukemia (AML) varies, ranging from 0.6%–46%. Leukocyte immunoglobulin-like receptor B4 (LILRB4) has been shown to be critical in orchestration of infiltration of AML cells into the CNS in animal models, however it is unknown if an association exists between LILRB4 and CNS involvement (CNS+) in human patients with AML. LILRB4 was measured by flow cytometry in a heterogeneous population of fifty-six AML patients. Patients were then followed clinically for the development of CNS + . LILRB4 was positive in 91 % of patients with CNS + compared to 38 % without CNS involvement (p < 0.002). In logistic analysis: age, BMI, serum albumin and positive LILRB4 were predictive for CNS+ OR, 95 % CI, p-value: 0.95, 0.92−0.99, p < 0.01; 0.85, 0.73−0.998, p < 0.05; 0.23, 0.066−0.78, p < 0.02; 16.46, 1.93–140.2, p < 0.02, respectively. This finding of the association of LILRB4 with CNS + in combination with earlier findings suggests that LILRB4 has a mechanistic role in infiltration of the CNS and may provide insight into the pathogenesis of AML seeding the CNS. Moreover, this proof of concept and the findings in the present study may lead to the development of innovative and novel therapies to improve the lives of patients with AML.
Chemotherapy-related hospitalizations in patients with advanced cancer are common, distressing, and costly. Methods to identify patients at high risk of chemotherapy toxic effects will permit ...development of targeted strategies to prevent chemotherapy-related hospitalizations.
To demonstrate the feasibility of using readily available clinical data to assess patient-specific risk of chemotherapy-related hospitalization.
Nested case-control study conducted from January 2003 through December 2011 at the Mass General/North Shore Cancer Center, a community-based cancer center in northeastern Massachusetts. The parent cohort included 1579 consecutive patients with advanced solid-tumor cancer receiving palliative-intent chemotherapy. Case patients (n = 146) included all patients from the parent cohort who experienced a chemotherapy-related hospitalization. Controls (n = 292) were randomly selected from 1433 patients who did not experience a chemotherapy-related hospitalization.
Putative risk factors for chemotherapy-related hospitalization-including patient characteristics, treatment characteristics, and pretreatment laboratory values-were abstracted from medical records. Multivariable logistic regression was used to model the patient-specific risk of chemotherapy-related hospitalization.
Chemotherapy-related hospitalization, as adjudicated by the oncology clinical care team within a systematic quality-assessment program.
A total of 146 (9.2%) of 1579 patients from the parent cohort experienced a chemotherapy-related hospitalization. In multivariate regression, 7 variables were significantly associated with chemotherapy-related hospitalization: age, Charlson comorbidity score, creatinine clearance, calcium level, below-normal white blood cell and/or platelet count, polychemotherapy (vs monotherapy), and receipt of camptothecin chemotherapy. The median predicted risk of chemotherapy-related hospitalization was 6.0% (interquartile range IQR, 3.6%-11.4%) in control patients and 14.7% (IQR, 6.8%-22.5%) in case patients. The bootstrap-adjusted C statistic was 0.71 (95% CI, 0.66-0.75). At a risk threshold of 15%, the model exhibited a sensitivity of 49% (95% CI, 41%-57%) and a specificity of 85% (95% CI, 81%-89%) for predicting chemotherapy-related hospitalization.
In patients initiating palliative chemotherapy for cancer, readily available clinical data were associated with the patient-specific risk of chemotherapy-related hospitalization. External validation and evaluation in the context of a clinical decision support tool are warranted.
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