Kumar, Shaji

Abstract The approach to patients with high-risk smoldering multiple myeloma (SMM) varies among clinicians; while some advocate early intervention, others reserve treatment at progression to multiple myeloma (MM). We aimed to describe the myeloma-defining events (MDEs) and clinical presentations leading to MM diagnosis among SMM patients seen at our institution. We included 406 patients diagnosed with SMM between 2013-2022, seen at Mayo Clinic, Rochester, MN. The 2018 Mayo 20/2/20 criteria were used for risk stratification. Median follow-up was 3.9 years. Among high-risk patients who did not receive treatment in the SMM phase (n=71), 51 progressed by last follow-up; the MDEs included: bone lesions(37%), anemia(35%), hypercalcemia(8%), and renal failure(6%); 24% met MM criteria based on marrow plasmacytosis (≥60%) and/or free light chain ratio (>100); 45% had clinically significant MDEs (hypercalcemia, renal insufficiency, and/or bone lesions). MM diagnosis was made based on surveillance labs/imaging(45%), testing obtained due to provider suspicion for progression(14%), bone pain(20%), and hospitalization/ED presentations due to MM complications/symptoms(4%). The presentation was undocumented in 14%. A high proportion (45%) of patients with high-risk SMM on active surveillance develop end-organ damage at progression. About a quarter of patients who progress to MM are not diagnosed based on routine interval surveillance testing.

AbstractBackgroundTobacco use is associated with adverse outcomes among patients diagnosed with cancer. Socioeconomic determinants influence access and utilization of tobacco treatment; little is known about the relationship between neighborhood socioeconomic disadvantage (NSD) and tobacco assessment, assistance, and cessation among patients diagnosed with cancer.MethodsA modified Cancer Patient Tobacco Use Questionnaire (C‐TUQ) was administered to patients enrolled in nine ECOG‐ACRIN clinical trials. We examined associations of NSD with (1) smoking status, (2) receiving tobacco cessation assessment and support, and (3) cessation behaviors. NSD was classified by tertiles of the Area Deprivation Index. Associations between NSD and tobacco variables were evaluated using logistic regression.ResultsA total of 740 patients completing the C‐TUQ were 70% male, 94% White, 3% Hispanic, mean age 58.8 years. Cancer diagnoses included leukemia 263 (36%), lymphoma 141 (19%), prostate 131 (18%), breast 79 (11%), melanoma 69 (9%), myeloma 53 (7%), and head and neck 4 (0.5%). A total of 402 (54%) never smoked, 257 (35%) had formerly smoked, and 81 (11%) were currently smoking. Patients in high disadvantaged neighborhoods were approximately four times more likely to report current smoking (odds ratio [OR], 3.57; 95% CI, 1.69–7.54; p = .0009), and more likely to report being asked about smoking (OR, 4.24; 95% CI, 1.64–10.98; p = .0029), but less likely to report receiving counseling (OR, 0.11; 95% CI, 0.02–0.58; p = .0086) versus those in the least disadvantaged neighborhoods.ConclusionsGreater neighborhood socioeconomic disadvantage was associated with smoking but less cessation support. Increased cessation support in cancer care is needed, particularly for patients from disadvantaged neighborhoods.

Abstract Venetoclax, a potent BCL‐2 inhibitor, is currently under development for treatment of t(11;14) Multiple myeloma (MM). The objective of this research was to investigate the exposure–response relationships of venetoclax for a phase 1/2 study evaluating venetoclax monotherapy or in combination with dexamethasone in relapsed or refractory MM. A total of 117 patients receiving venetoclax at 300, 600, 800, 900, or 1200 mg were included in the analysis. The impact of venetoclax exposures on efficacy (objective response rate [ORR], progression‐free survival [PFS] and overall survival [OS]) as well as safety (treatment‐emergent adverse effects (grade ≥3) of neutropenia, infection, and any grade of serious treatment‐emergent adverse effects) was evaluated. In the t(11;14)‐positive subpopulation, venetoclax exposure relationships to PFS and OS indicated a trend of longer PFS and OS with higher exposures. Moreover, logistic regression analyses for clinical response (ORR and ≥VGPR rate) demonstrated a statistically significant ( p < 0.05) relationship with exposure. Evaluation of the exposure‐safety relationships demonstrated a lack of a relationship between venetoclax exposures (AUC avg ) and grade ≥3 infections, grade ≥3 neutropenia, grade ≥3 treatment‐emergent adverse events or any grade serious treatment‐emergent adverse events. These findings support further study of venetoclax at 800 mg QD dose in combination with dexamethasone in the t(11;14)‐positive patient population where increased efficacy was observed without an increase in safety events.Clinical Trial: NCT01794520 registered 20 February 2013.

Abstract Objectives Fluorescence in situ hybridization (FISH) for plasma cell neoplasms (PCNs) requires plasma cell (PC) identification or purification strategies to optimize results. We compared the efficacy of cytoplasmic immunoglobulin FISH (cIg-FISH) and fluorescence-activated cell sorting FISH (FACS-FISH) in a clinical laboratory setting. Methods The FISH analysis results of 14,855 samples from individuals with a suspected PCN subjected to cytogenetic evaluation between 2019 and 2022 with cIg-FISH (n = 6917) or FACS-FISH (n = 7938) testing were analyzed. Results Fluorescence-activated cell sorting–FISH increased the detection rate of abnormalities in comparison with cIg-FISH, with abnormal results documented in 54% vs 50% of cases, respectively (P &lt; .001). It improved the detection of IGH::CCND1 (P &lt; .001), IGH::MAF (P &lt; .001), IGH::MAFB (P &lt; .001), other IGH rearrangements (P &lt; .001), and gains/amplifications of 1q (P &lt; .001), whereas the detection rates of IGH::FGFR3 fusions (P = .3), loss of 17p (P = .3), and other abnormalities, including hyperdiploidy (P = .5), were similar. Insufficient PC yield for FISH analysis was decreased between cIg-FISH and FACS-FISH (22% and 3% respectively, P &lt; .001). Flow cytometry allowed establishment of ploidy status in 91% of cases. In addition, FACS-FISH decreased analysis times, workload efforts, and operating costs. Conclusions Fluorescence-activated cell sorting–FISH is an efficient PC purification strategy that affords significant improvement in diagnostic yield and decreases workflow requirements in comparison with cIg-FISH.