Clinical Lymphoma, Myeloma & Leukemia最新文献

Background: Large B cell lymphoma (LBCL) is the most common form of lymphoma. Polatuzumab vedotin (polatuzumab) is an effective therapy for patients diagnosed with LBCL; however, only limited information regarding pathologic features detected by clinical laboratory assays is available to determine which patients are most likely to benefit from polatuzumab based therapies.

Patients and methods: We collected data from real world patients with relapsed or refractory LBCL whose tumors underwent next generation sequencing and were treated with polatuzumab based therapy at a single large academic cancer center. Tumor and patient characteristics were analyzed to look for factors that predict response to polatuzumab based therapies.

Results: We identified high grade B cell lymphoma (HGBL) -NOS or MYC/BCL2 histology and presence of MYC rearrangement as factors that predict inferior response to polatuzumab based therapy. Patients with germinal center B cell of origin (GCB COO) LBCL without these factors had a high response rate (73%) to polatuzumab based therapy.

Conclusion: In a single center real world retrospective analysis of R/R LBCL patients with available genomic data, polatuzumab based therapy may be less effective in patients with HGBL-NOS or MYC/BCL2 histology and MYC rearrangements, but not in patients with GCB COO LBCL without these features. Routine performance of more comprehensive pathologic analysis of tumors may inform the use of polatuzumab based therapy in patients with LBCL.

Background: Haploidentical donor transplantation (HIDT) or cord blood transplantation (CBT) are common alternatives for patients lacking human-leukocyte antigen (HLA)-matched donors. In addition to the donor source, NK cell alloreactivity due to HLA-mismatch setting may affect outcomes in alternative-donor hematopoietic cell transplantation (HCT). However, a limited number of studies have evaluated their impacts in adult acute lymphoblastic leukemia (ALL).

Objectives: We aimed to assess the effects of donor source and KIRL-MM on outcomes of alternative-donor HCT, with a special focus on adult ALL.

Study design: We retrospectively compared clinical outcomes between HIDT (n=47) and double unit CBT (DCBT) (n=134). Patients received fludarabine and busulfan-based reduced toxicity conditioning before HIDT, and TBI-based myeloablative conditioning before DCBT. KIR ligands were determined using a web-based calculator. For DCBT, donor KIR ligand groups were defined by the dominant CB unit after engraftment.

Results: After a median follow-up of 39.4 months, DCBT showed higher 3-year non-relapse mortality (NRM) (22.8% vs. 9.0%, p=0.038), whereas the cumulative incidence of relapse (CIR) was significantly higher in HIDT (47.9% vs. 18.9%, p<0.001). Estimated disease-free survival (DFS) was comparable (DCBT 58.5% vs. HIDT 44.3%, p=0.106). GVH direction KIRL-MM showed lower incidence of acute GVHD in both HIDT and DCBT. However, GVH direction KIRL-MM was associated with poorer DFS (37.2% vs. 66.0%, p=0.008) only in the DCBT subgroup, mostly due to specifically higher NRM rate (35.0% vs 18.4%, p=0.057).

Conclusion: Our study supports the usefulness of DCBT in the HIDT-dominant era and suggests potential ways to improve survival outcomes of DCBT.

Background: Dementia, a growing global health issue, affects older adults and specific groups like long-term cancer survivors. The link between cancer survival and dementia is debated. Multiple myeloma (MM), a common blood cancer in older adults, is often linked with cognitive issues. This study investigated dementia incidence in long-term MM survivors using Korean national data.

Methods: A retrospective case-control study used data from the Korea National Health Insurance Service (KNHIS), covering about 50 million Koreans. Patients diagnosed with MM between 2009 and 2020 formed the case cohort, while the control cohort included matched individuals without MM using propensity-score matching. Analyzing baseline characteristics, comorbidities, and socioeconomic status, the primary outcome was dementia incidence identified via ICD-10 codes. Statistical methods included Kaplan-Meier plots, cause-specific and Fine-Gray subdistribution hazard models, and a 3-year landmark analysis for immortal time bias.

Results: The study included 33,864 patients, with 16,932 in each cohort. The overall cumulative dementia incidence was lower in the MM cohort compared to controls. However, in the first 3 years, MM patients had a higher dementia risk (HR: 1.711, 95% CI, 1.562-1.874) than controls. After 3 years, the risk significantly decreased (HR: 0.625, 95% CI, 0.560-0.696). Age-specific analysis showed a consistent pattern, particularly among MM patients aged 70-79, where dementia risk increased post-3 years.

Conclusion: This study reveals a lower long-term dementia risk in MM survivors compared to non-MM individuals. Further prospective studies are needed to confirm these findings and explore the underlying mechanisms.

Introduction: Plasma cell leukemia (PCL) is a rare malignancy with poor overall survival (OS). Recently, its diagnostic criteria were revised by lowering the threshold of circulating plasma cells from ≥ 20% to ≥ 5%.

Methods: Between 2010 and 2024, patients with primary PCL (pPCL) and secondary PCL (sPCL) were identified at a tertiary center. We retrospectively analyzed baseline characteristics, treatment, and survival in months (m).

Results: We identified 30 patients with pPCL and 29 patients with sPCL. The median time to sPCL in patients who received Daratumumab (Dara)-containing regimens for multiple myeloma was 46.8m compared with 12.3m in patients who did not (P=0.007). Of the whole cohort, 51.9% received an induction regimen with novel agents without chemotherapy. Of the evaluable patients with pPCL and sPCL, 82.1% (23/28) and 64.7% (11/17) achieved partial response or better respectively. Median progression free survival was significantly worse in patients with sPCL than pPCL (2.2 vs. 38.3 months; HR 0.16; 95% CI (0.07-0.35), P < .001). Median OS was also worse in patients with sPCL compared with pPCL (3.1 months vs. NR [not reached]; HR 0.09; 95%CI 0.04-0.23, P < .001). The median post-SCT survival for patients with pPCL was NR compared with 6.7m for patients with sPCL (HR 0.17; 95% CI (0.03-0.83), P = .03). Dara-refractory status was associated with worse OS (HR 5.63; 95% CI (2.75-11.51), P < .0001).

Conclusion: Outcomes of pPCL are improving but remain dismal for sPCL. We explored the role of novel agents, especially Dara, in the treatment of PCL. More prospective trials are needed to improve its outcomes.

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: 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.

The survival outcomes of patients with chronic myeloid leukemia (CML) have significantly improved due to the introduction of adenosine triphosphate (ATP) -competitive ABL1 tyrosine kinase inhibitors (TKIs). However, several patients with CML eventually develop treatment resistance or intolerance during the course of ATP-competitive ABL1 TKI treatment. ABL1 TKIs inhibit other tyrosine kinases via their off-target effects. This mechanism leads to the development of adverse events, which may result in treatment discontinuation. Asciminib is a first-in-class STAMP (specifically targeting the ABL myristoyl pocket) inhibitor used in patients with chronic-phase CML who exhibit resistance or intolerance to two prior TKI therapies. Asciminib was found to have excellent efficacy and safety therapeutic profiles. The lack of comprehensive reviews about asciminib, thus, the current study aimed to evaluate the clinical and preclinical evidence of the efficacy and safety of asciminib.

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.

Background: The number of clinical studies in the Western world has been declining the last decade. Clinical studies offer valuable opportunities for cancer patients to access new treatments and serve as arenas for learning and competence development for health care workers. In addition to this, clinical studies can significantly contribute to financial savings for the health care system through the provision of drugs. The extent of these savings have not been evaluated before.

Materials and methods: We assessed the financial savings from drugs provided in clinical studies conducted at Oslo Myeloma Center between 2015 and 2021. Only drugs that had marketing license or another equivalent drug with marketing license were considered to estimate savings.

Results: A total of 314 patients across 24 different studies were given treatment with drugs possessing marketing license. Drugs approved for clinical use and reimbursed by the national health care system gave a financial saving of 20.3 million USD and was considered a direct saving. Drugs not approved for clinical use, but having equivalent approved alternatives yielded a financial saving of 4.7 million USD.

Conclusion: Clinical studies not only offer new opportunities for patients and advancements in medical treatment and knowledge but also contribute significantly to financial saving for the health care system through reduced drug expenses.

Background: Over the last 15 years, improvements in patient management and treatments have been associated with longer survival in patients with multiple myeloma (MM). The Connect MM Registry is a long-running, US, multicenter, prospective observational cohort study of patients with newly diagnosed MM (NDMM). We assessed the demographics, clinical characteristics, and treatment patterns of long-term survivors (LTS) enrolled in this registry.

Methods: Adults with NDMM (n = 3,011) were enrolled from 250 community, academic, and government sites across the US from 2009-2016. Baseline characteristics, treatment patterns, quality of life (QoL), and overall survival (OS) were examined among LTS, defined as patients with follow-up of ≥ 8 years after enrollment.

Results: As of February 7, 2023, 518 patients were LTS and 2,493 were non-LTS. LTS were generally younger and had better performance status at enrollment compared with non-LTS. Most (65%) LTS received stem cell transplants and few (2%) experienced disease progression within 6 months of starting first line of therapy. At data cutoff, 63% of LTS were still on treatment at their most recent visit. QoL scores and QoL questionnaire completion rates were consistently higher among LTS than non-LTS. The estimated 8-year OS rate of all patients enrolled in the registry was 40%, comparable to an observed 8-year survival of 39% from the Surveillance, Epidemiology, and End Results (SEER) database.

Conclusion: This analysis provides insights on long-surviving patients with MM using real-world data and therefore presents generalizability beyond data obtained in long-term follow-up of clinical trials, underscoring the need for longitudinal follow-up through registries.