Clinical Lymphoma, Myeloma & Leukemia最新文献

Background: This study aimed at describing the demographic and clinical characteristics, treatment patterns and overall survival of patients with MM in Brazil to identify gaps in the disease diagnosis and treatment.

Methods: MMyBRAve (NCT03506386) was a multicenter, observational study of patients diagnosed with MM in Brazil between January 2008 and December 2016, with data collection between August 2018 and September 2019 at 17 participating centers.

Results: Of 943 patients included, 914 had complete data for overall survival (OS) analysis. The most used frontline regimens were cyclophosphamide, thalidomide and dexamethasone; bortezomib, cyclophosphamide and dexamethasone; and thalidomide and dexamethasone. After a median follow-up of 63 months, the median OS from diagnosis was 70 months. These results indicate continuous improvements in comparison with previous observational studies from Brazil. The median OS in transplantation-ineligible (N = 491) and eligible (N = 452) patients were 49 and 93 months, respectively (hazard ratio [HR] = 0.52; 95% confidence interval [CI], 0.43 to 0.63; P < .001). The median OS also differed between patients with and without known prognostic factors.

Conclusion: Despite the improvements, our results suggest that access to novel agents and transplantation continue to hinder further progress in patient outcomes in Brazil and countries with similar health-care constraints.

Background: Disparities in access to triplet and quadruplet therapy for multiple myeloma (MM) patients remain a challenge in the United States. We aimed to investigate demographic and socioeconomic factors influencing treatment access using NCDB data.

Patients and methods: We analyzed 101,867 MM patients diagnosed between 2004 and 2020. Multinomial logistic regression and multivariable cox regression were employed to assess factors influencing treatment access and survival, respectively.

Results: Black patients exhibited significantly lower odds of receiving triplet and quadruplet therapy compared to White patients. Socioeconomic factors such as insurance status and household income also influenced treatment access. However, Black and Hispanic patients demonstrated better survival outcomes despite disparities in access.

Conclusion: Racial, socioeconomic, and insurance-related disparities persist in access to optimal MM therapy in the USA. Addressing these barriers is essential for ensuring equitable healthcare delivery and improving patient outcomes.

Introduction: Obinutuzumab is hypothesized to improve progression-free survival (PFS) combined with bendamustine induction in mantle cell lymphoma (MCL). Measurable-residual disease (MRD) testing may predict benefit from maintenance therapy.

Methods: Adults (≥ 18 years) with untreated MCL ineligible for intensive therapies received 4 to 6 cycles of bendamustine + obinutuzumab (BO) followed by consolidation obinutuzumab (CO). Restaging after CO included MRD assessment by next-generation sequencing of bone marrow aspirate (BMA) and peripheral blood (PB). Maintenance obinutuzumab (MO) was omitted for patients with imaging complete response (CR) and MRD-negativity in PB/BMA. All other patients received 8 cycles MO. Primary endpoint is PFS; secondary endpoints are response rates, overall survival, and estimation of MRD status.

Results: Twenty-one patients enrolled, with median age 70 years and stage IV disease in 95%. Twenty patients completed BO; 10 patients received MO per protocol. Six patients did not complete MO due to progression (n = 4), infection (n = 1) and carcinoma (n = 1). Overall response is 95% (75% CR, 20% partial response). Concordance rate between post-consolidation MRD testing in PB and BMA was 70%. After a median follow-up of 43.9 months, median PFS is 46.5 months. The observed difference between 2-year PFS in groups receiving MO versus observation was not statistically significant (HR 0.45, 95% CI, 0.10-1.91). Most common grade 3/4 toxicities were neutropenia, leukopenia, and infections.

Conclusions: BO is a tolerable induction regimen with higher rates of CR compared with historical rates with bendamustine + rituximab. Omission of MO did not worsen outcomes in patients achieving MRD-negative status after nonintensive induction/consolidation therapy.

Introduction: We performed a retrospective analysis of patients with multiple myeloma (MM) receiving palliative radiotherapy (RT) and assessed factors associated with local control, with a focus on dose/fractionation and cytogenetics.

Materials and methods: We included patients who received palliative RT for MM at our institution. Cytogenetics were collected via fluorescence in situ hybridization. Follow-up imaging was used to assess local control.

Results: A total of 239 patients with 362 treated lesions were included. Eighty-six (36.0%) patients had high-risk cytogenetics. Most lesions received 20 Gray (Gy) in 5 fractions (131, 36.2%), 8 Gy in 1 fraction (93, 25.7%), or 30 Gy in 10 fractions (48, 13.3%). At a median follow-up of 4.3 years, 4-year local progression was 13.4% (95% confidence interval [CI]: 10.3-17.5). No cytogenetic abnormalities were correlated with local progression, nor were double- and triple-hit status. There was a nonsignificant trend toward association between number of treated lesions and local progression (HR for >3 vs. 1: 2.43 [95% CI: 0.88-6.74], P = .059). Among patients with >3 treated lesions, equivalent dose in 2 Gy fractions ≥20 Gy reduced progression (HR: 0.05 [95% CI: 0.01-0.23], P = .0001).

Conclusion: In this large study of patients with MM, modern palliative RT achieved excellent rates of long-term local control. Although there was no dose-response observed in the overall cohort, patients with high volume symptomatic disease may benefit from EQD2 ≥20 Gy. High-risk cytogenetics did not appear to influence radioresponsiveness, and standard radiation doses appear to be effective for all MM patients regardless of cytogenetics.

Background: Prognostic models in peripheral T cell lymphoma (PTCL) have identified biological factors including age, performance status, LDH, and BM involvement as prognostic for survival. The association of social determinants of health (SDH), on PTCL outcomes remains unexplored.

Methods: To evaluate the impact of actionable SDH on PTCL mortality across race groups, we conducted a retrospective cohort study that included all White, Hispanic, Asian/Pacific Islander (PI) and Black adult patients with nodal PTCLs , diagnosed 2000-2020, in California. We utilized Chi² and Wilcoxon rank-sum tests for descriptive metrics and Kaplan-Meier statistics for mortality estimation. Regression models included patient- (age, sex, race, stage, Charlson Comorbidity Index, histology, treatment, academic center treatment, payer), and neighborhood-level factors (socioeconomic (SES) quintile, proportion without a high school diploma, and rural/urban). Risk factors significant in univariate regression of P < .10 were incorporated into the multivariable model.

Findings: Our analysis included 6158 patients: 51.8% White, 25.8% Hispanic, 14.7% Asians/PI, and 7.6% Black. Hispanics exhibited the longest median survival (33 months) followed by Whites, Blacks, and Asian/PI (25, 20, and 14 months, respectively; P = .011). Risk factors independently associated with inferior lymphoma-specific survival (LSS) included Asian/PI compared with NH Whites (HR, 1.23; 95% CI, 1.10-1.34; P = .0002), AITL/ALCL compared with PTCL, NOS (AITL HR, 1.14; 95% CI, 1.02-1.25; P = .011; ALCL HR, 1.15; 95% CI, 1.04-1.26; P = .004), academic compared to nonacademic facility-type (HR 0.71; 95% CI, 0.64-0.77; P < .01), Medicare compared with uninsured (HR 1.48, 95% CI, 1.25-1.73; P < .01), and the lowest 3 compared to the highest education quartiles (Q2 HR 1.13; 95% CI, 1.01-1.25; P = .021; Q3 HR 1.14; 95% CI, 1.02-1.26; P = .018; Q4 HR 1.22; 95% CI, 1.08-1.36; P < .001). In the least resourced patients, histology, treatment, treatment facility-type, payer and education were independently prognostic for LSS. Academic center treatment was associated with a striking improvement in LSS (academic institution: yes = 101 months, no = 17 months; P < .01).

Interpretation: Treatment facility-type, payer and education, areindependent actionable SDH for PTCL mortality. Treatment center-type had the strongest prognostic association with LSS, conferring a risk reduction of PTCL mortality by nearly 30%.

Introduction: Multiple myeloma patients aged 80 years and older are a population more prone to comorbidities and frailty. We aim to describe the real-life management and outcomes of this population. EMMY is a descriptive large-scale study.

Patients: Between 2017 and 2021 we included 4383 patients of which 894 (20.3%) were aged ≥ 80 years. Four cohorts of patients aged ≥ 80 years were analysed: line 1 (L1), line 2 (L2), line 3 (L3) or line 4+ (L4+).

Results: The proportion of patients ≥ 80 years old was 20.8% in L1, 21.3% in L2, 20.9% in L3 and 17.8% in L4+. L1 patients received more treatment including a proteasome inhibitor (PI) (42.9%), L2 patients received mainly an immunomodulator (IMID) (65.9%) or an anti-CD38 (31.5%). For L3, IMID was used in 71.4% than an anti-CD38 (33.5%). L4+ patients received a PI (40.6%), IMID (33.2%) or an anti-CD38 (29.1%). Regarding efficacy, the median progression-free survival was 18.4 months in L1, 15.1 months in L2, 10.4 months in L3 and 6.5 months in L4+. The median overall survival was 49 months in L1, 31.3 months in L2, 21.4 months in L3 and 13.6 months in L4+.

Conclusion: EMMY cohort confirmed that patients ≥ 80 years of age represent an important proportion of MM patients, in the de novo or relapse setting. This study is an important step in improving our comprehension and management of treatment in elderly patients.

Background: Chimeric antigen receptor T-cell (CAR-T) therapies are available for patients with Non-Hodgkin Lymphoma (NHL); however, their use has been limited in accessibility due to nondisease factors.

Patients & methods: We conducted a retrospective study evaluating the influence of sociodemographic factors on access and outcomes after CAR-T therapy for adult patients with B-cell NHL in our institution treated between 2016 and 2023.

Results: Among 154 patients treated with CAR-T, 43% were older than 65 years, 68% male, and 14% non-White (including Hispanic). Of those under 65, 66% had private insurance, while 82% over 65 had Medicare. Most patients (85%) were from in-state, 29% from areas below the national poverty level and 18% from nonmetropolitan areas. Distance to the treatment center was greater than 30, 60 or 120 miles for 52%, 40% and 29% of patients, respectively. No significant differences were found in the use of commercial versus investigational products among racial/ethnic minorities or those living >60 miles from the center. However, patients from nonmetropolitan areas and those below the national poverty level were less likely to receive commercial products. With a median follow-up of 11 months, the 1-year overall survival (OS) was 63.2% (95^th CI 59.9%-66.8%). Poverty was associated with lower 1-year OS (HR 0.4, 95^th CI 0.17-0.90, P = .031).

Conclusion: Our study shows that CAR-T therapy can be delivered across sociodemographic barriers and underscores the importance of considering social determinants of health to optimize access for all patients.

Background: Short diagnosis-to-treatment interval (DTI) is associated with high-risk disease and poor survival in diffuse large B-cell lymphoma (DLBCL). There is a paucity of literature on DTI and survival in DLBCL treated with first-line DA-R-EPOCH. We hypothesized that rapid initiation of DA-R-EPOCH in aggressive and high-risk DLBCL mitigates the adverse prognostic implication of short DTI.

Patients and methods: We retrospectively examined the association of DTI, categorically (short DTI ≤ 14 and long > 14 days) and continuously, with clinical features and survival outcomes in DLBCL treated with first-line DA-R-EPOCH at our institution.

Results: A total 190 patients were analyzed, 21% with high-grade DLBCL subtypes, 56% IPI ≥ 3, and median DTI of 13 days. The short DTI cohort contained more patients with IPI ≥ 3, bulky disease, and elevated LDH. When analyzed categorically and continuously, DTI was not associated with significant differences in PFS or OS. There was significant multivariable interaction between bulky disease, DTI, and PFS (P = .033), with improved PFS in patients with bulky disease in the short DTI cohort.

Conclusion: We found that negative prognostic implications of DTI are mitigated in DLBCL patients treated with first-line DA-R-EPOCH, suggesting that urgent initiation of DA-R-EPOCH in high-risk DLBCL, including bulky disease, may improve survival. Our study's shorter DTI compared with DTIs reported in prospective DLBCL trials highlights DTI as a marker of external validity in clinical trial results. Future trials should implement protocols encouraging shorter, realistic DTIs to avoid selection bias against high-risk patients who are unable to delay treatment.

Background: Tyrosine kinase inhibitors (TKIs) are the mainstay treatment for chronic myeloid leukemia in chronic phase (CML-CP). Asciminib, an ABL/BCR::ABL1 inhibitor which binds to the myristoyl pocket, was recently approved in the US for patients with CML-CP previously treated with ≥2 TKIs or with the T315I mutation. This study described treatment patterns and real-world clinical outcomes among patients with CML-CP treated with asciminib in US clinical practice.

Methods: Electronic health record data from adult patients with CML-CP who initiated asciminib after ≥2 prior TKIs, without the T315I mutation, were obtained from the Flatiron Health database. Time-to-treatment discontinuation and molecular response (MR; time-to-BCR::ABL ≤0.1% and time-to-BCR::ABL1 ≤1%, separately) were evaluated from asciminib initiation (index date) using Kaplan-Meier analyses.

Results: Overall, 97 patients initiated asciminib (median age: 63 years, 50.5% female, 64.9% White) after either 2 (47.4%) or 3 (24.7%), or ≥4 (27.8%) prior TKIs. In total, 85.7% and 78.1% of patients remained on asciminib by 12- and 24-weeks postindex, respectively. Among patients with ≥1 MR assessment postindex, 31.3% (95% confidence interval [CI]: 21.6%, 43.9%) and 49.7% (95% CI: 38.1%, 62.6%) achieved or maintained BCR::ABL1 ≤0.1%, while 51.3% (95% CI: 40.1%, 63.6%) and 64.2% (95% CI: 52.6%, 75.6%) achieved or maintained BCR::ABL1 ≤1%, by 12- and 24-weeks, respectively.

Conclusions: Results of this real-world study describing clinical outcomes among patients with CML-CP treated with asciminib after ≥2 prior TKIs in the US demonstrated that asciminib was well-tolerated and effective. These findings were consistent with results from the ASCEMBL trial.

Multiple myeloma is a challenging hematological malignancy, with ongoing efforts toward finding a cure. Dr. Raymond Alexanian has been instrumental in advancing the understanding and treatment of multiple myeloma through his pioneering research. Trained at Dartmouth College and Harvard Medical School, Dr. Alexanian MD Anderson Cancer Center career spanned nearly 5 decades. He developed the highly effective MP (melphalan-prednisone) regimen, which became a standard treatment for years. Dr. Alexanian's exploration of steroids, particularly high-dose dexamethasone, and the collaboration with Dr. Bart Barlogie led to the development of the VAD (vincristine, doxorubicin, and dexamethasone) regimen, significantly improving outcomes for refractory cases. He also contributed to the establishment of high-dose melphalan with autologous stem cell transplantation. Dr. Alexanian's work identified critical prognostic factors and contributed understanding indolent and localized myeloma. His efforts in evaluating new agents, including thalidomide and bortezomib, further enhanced treatment options. Beyond research, his compassionate patient care and advocacy have had a profound impact. Dr. Alexanian's legacy continues to inspire advancements in multiple myeloma treatment, with his innovative approaches reshaping the field and fostering the pursuit of a cure.