Clinical Lymphoma, Myeloma & Leukemia最新文献

Introduction: Follicular lymphoma typically affects patients in their fifth, sixth, and seventh decades of life and carries a median survival of 10 years. Rituximab induction followed by maintenance has been increasingly used in follicular lymphoma for patients with low tumor burden progression who wish to receive treatment but want to avoid the side effect profile of chemotherapy. Data on the efficacy of this course is limited for patients previously treated with rituximab as well as those with intermediate risk disease. Here we present data from a single center on the efficacy of induction and maintenance rituximab in a cohort with a mix of intermediate and low risk patients.

Patients and methods: 26 patients with FL underwent a course of induction rituximab followed by maintenance from 2007 to 2024. 15% were bulky by GELF, 27% were high risk by FLIPI, and 35% had received prior treatment with all but one of the previously treated patients having received rituximab.

Results: Estimated median 2 year PFS was 71%, TTNT was 68%, and OS was 88%. Median follow up time was 1.72 years. Eight patients deepened their response during maintenance to a CR.

Conclusion: In this study, intermediate and low risk FL patients responded well to induction rituximab followed by maintenance with survival comparable to past studies of higher risk patients. This study provides evidence that even those patients previously treated with rituximab can benefit from retreatment rituximab with maintenance.

Background: This indirect treatment comparison evaluated epcoritamab plus gemcitabine and oxaliplatin (Epcor+GemOx) versus rituximab (R)-GemOx in patients with transplant-ineligible relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Methods: Individual patient data (IPD) for Epcor+GemOx from EPCORE NHL-2 Arm 5 (NCT04663347) were compared with clinical practice data for patients treated with R-GemOx using 2 methodologies: a matching-adjusted indirect comparison (MAIC) using published aggregate data from clinical sites in France (Cazelles et al. Lymphoma. 2021;62:2161) and inverse probability of treatment weighting (IPTW) using IPD from the US-based COTA database (COTA Healthcare). Outcomes included objective response rate (ORR), complete response (CR) rate, progression-free survival (PFS), and overall survival (OS).

Results: In the MAIC, after adjustment, Epcor+GemOx versus R-GemOx had significantly higher ORR (86.8% vs 38.3%; relative risk [RR], 2.27 [95% confidence interval (CI), 1.76-2.93]; P < .0001) and CR rate (71.2% vs 32.7%; RR, 2.18 [95% CI, 1.61-2.96]; P < .0001). Median PFS was 26.7 versus 4.8 months (hazard ratio [HR], 0.38 [95% CI, 0.22-0.67]; P < .001); median OS was not reached with Epcor+GemOx versus 10.0 months with R-GemOx (HR, 0.54 [95% CI, 0.29-1.00]; P = .05). In the IPTW, Epcor+GemOx versus R-GemOx had significantly higher ORR (88.5% vs 35.6%; RR, 2.48 [95% CI, 1.80-3.43]; P < .0001), CR rate (63.9% vs 10.2%; RR, 6.25 [95% CI, 3.08-12.68]; P < .0001), median PFS (11.2 vs 2.4 months; HR, 0.23 [95% CI, 0.15-0.36]; P < .001), and median OS (21.6 vs 8.3 months; HR, 0.47 [95% CI, 0.30-0.74]; P = .002).

Conclusion: Epcor+GemOx provides significantly greater response rates and survival outcomes compared with R-GemOx in patients with transplant-ineligible R/R DLBCL.

Secondary breast cancer (SBC) is emerging as the most frequent solid tumour in female survivors of Hodgkin lymphoma (HL) treated with chest radiotherapy (RT). Women irradiated with ≥10 Gy before the age of 30 accumulate risks that rival those carried by BRCA1/2 mutation carriers, with excess cases appearing ∼8 years after RT and persisting lifelong. This review weaves together epidemiological data, mechanistic evidence and clinical studies to elucidate how radiation dose and field, age at exposure, systemic regimens, host genomics and micro-environmental factors interact to drive SBC. Radiation-associated tumours display a distinctive profile-earlier onset, frequent bilaterality-posing unique therapeutic and prognostic challenges. We discuss current surveillance recommendations of annual mammography plus breast MRI from age 25 (or 8 years post-RT) and examine preventive strategies ranging from RT de-escalation and cardioprotective chemotherapy to lifestyle modification and selective chemoprevention. Finally, we highlight emerging imaging and molecular biomarkers-most notably MRI background parenchymal enhancement and polygenic risk scores-that may enable a shift from 1-size-fits-all follow-up to precision survivorship care.

Introduction: The coexistence of solid tumors and multiple myeloma (MM) presents diagnostic and therapeutic challenges; however, data on clinical outcomes in this population remain limited. This study aimed to evaluate the clinical characteristics and survival outcomes of patients with newly diagnosed multiple myeloma (NDMM) who had synchronous or prior solid tumor malignancies.

Methods: A retrospective analysis was conducted on 41 NDMM patients with a documented history of solid tumor, classified as either concurrent (diagnosed within 6 months) or prior. Clinical characteristics, treatment patterns, and outcomes were evaluated. Patients were stratified according to the timing of solid tumor diagnosis.

Results: The median age was 66 years, with a male predominance (58.5%). Breast (24.4%), lung (17.1%), colon, and prostate cancers (9.8% each) were the most common solid tumors. Extramedullary disease was observed only in the synchronous group (100% vs. 0%). Autologous transplantation was performed significantly less frequently in the synchronous group (26.3% vs. 73.7%, P = 0.041). Lenalidomide maintenance therapy was underutilized in patients with synchronous malignancies, reflecting possible clinical hesitation. Myeloma-related mortality occurred in 17.1% of patients, with a median overall survival of 48 months (range: 16-80), and no significant survival difference between synchronous and patient with prior solid tumor history group.

Conclusion: The presence of synchronous solid tumors in NDMM patients is associated with a higher rate of extramedullary disease and may influence clinical decision-making, highlighting the need for multidisciplinary management and individualized treatment strategies. Furthermore, extramedullary involvement in MM should prompt evaluation for a potential coexisting solid malignancy.

Background: The management of relapsed / refractory myeloma particularly those who are heavily pretreated and penta-refractory has experienced a paradigm change with the advent of bispecific antibodies targeting B-cell maturation antigen (BCMA), offering new hope for these patients. The diverse experiences in the use of bispecific antibodies across Asian countries/regions underscore the complexities of integrating these therapies into clinical practice. With limited availability and varying access through clinical trials, compassionate access programmes and early commercial use, these agents are demonstrating impressive efficacy, yet present unique challenges in widespread adoption of these agents.

Methods: A roundtable discussion among myeloma experts from Asia has highlighted consistent efficacy but also raised concerns about the durability of response and the management of associated toxicities and infections.

Results: These discussions emphasize the need for ongoing research to better understand the nuances of treatment sequencing and patient selection.

Conclusions: The insights gained will contribute to developing strategic frameworks and consensus guidelines that can effectively guide clinicians in optimizing outcomes for myeloma patients in diverse healthcare settings.

Background: Tyrosine kinase inhibitors (TKIs) are essential therapies for chronic myeloid leukemia (CML), yet their safety during pregnancy remains poorly characterized. We aimed to address this gap by providing pharmacovigilance data using the FDA Adverse Event Reporting System (FAERS).

Methods: We conducted a comprehensive pharmacovigilance analysis of pregnancy-related adverse events (AEs) reported to FAERS between January 2001 and December 2024. Reports involving female patients exposed to imatinib, dasatinib, nilotinib, ponatinib, bosutinib, or asciminib were extracted. Pregnancy-related AEs were categorized into maternal and fetal outcomes and presented descriptively. Disproportionality analyses were also performed for 2022-2024 to determine only the more relevant AEs in contemporary clinical practice. Reporting odds ratios (RORs) with 95% confidence intervals (CI) were used to quantify associations.

Results: A total of 651 relevant pregnancy-related AEs were identified between 2001 and 2024, with imatinib accounting for the majority (n = 450), followed by nilotinib (n = 118), dasatinib (n = 64), ponatinib (n = 13), bosutinib (n = 4), and asciminib (n = 2). The most frequently reported maternal AEs were abortion (40.6%) and polyhydramnios (4.3%), while the most frequent perinatal complications included premature delivery (33.6%) and low birth weight (4.4%). In the disproportionality analysis (2022-2024), imatinib was significantly associated with pregnancy-related AEs (ROR 3.47; 95% CI: 1.49-8.05).

Conclusion: This pharmacovigilance analysis suggests a signal of pregnancy-related adverse events with imatinib, while evidence for other TKIs remains limited. Given the paucity of data, results should be interpreted with caution. Larger studies are needed to confirm these findings.

Background: Venous thromboembolism (VTE) is an important complication in newly diagnosed multiple myeloma (NDMM), particularly during the first year after diagnosis. Existing risk assessment models show limited predictive accuracy. This study developed a novel risk scoring system using complementary approaches to improve VTE risk prediction in NDMM.

Methods: We retrospectively analyzed 225 NDMM patients from 4 hospitals (2014-2019) to develop a prediction score for first-year VTE. The model was built using Least Absolute Shrinkage and Selection Operator (LASSO) regularization with variables showing P < .25 in univariate analysis. Performance was assessed using area under the curve (AUC) and Hosmer-Lemeshow test. IMPEDE-VTE and SAVED scores were calculated for comparison.

Results: Among 225 patients (median age 68 years), 32 (14%) developed VTE, predominantly pulmonary embolism (71%) within the first year after diagnosis. The LASSO model had a c-statistic of 0.86 and identified ECOG ≥ 1, high R-ISS stage, high-dose dexamethasone (> 160 mg per cycle), Lactate dehydrogenase (LDH) > 370 IU/L, immunoparesis, spinal cord compression, and paralysis as independent predictors (AUC: 0.86). LASSO-derived PREVEMM score significantly outperformed existing tools (AUC: 0.88 vs 0.61 for both IMPEDE-VTE and SAVED).

Conclusion: PREVEMM score demonstrates superior VTE risk stratification capabilities, supporting its potential clinical utility for individualized thromboprophylaxis in NDMM.

Background: This study explored financial toxicity and its association with treatment satisfaction among a longitudinal cohort of patients with multiple myeloma (MM).

Patients and methods: The multiple myeloma research foundation (MMRF) CureCloud initiative (NCT03657251) is an observational study which collects biospecimens, clinical data, and patient reported outcomes (PROs). Participants completed the Comprehensive Score for Financial Toxicity (COST) and the Cancer Therapy Satisfaction Questionnaire (CTSQ).

Results: At the initial time point, 214 participants completed the PROs. The mean age was 68, 60% were male, and 94% were white. The median time from MM diagnosis to the baseline survey completion was 6 years. The mean COST score was 29 (SD=10) and 37% of the patients were considered to be experiencing financial toxicity. Younger patients (P < .01) and those residing in areas with lower median household incomes (P = .01) were more likely to be experiencing financial toxicity. Participants experiencing financial toxicity reported lower satisfaction with their therapy, with a mean CTSQ score 6.7 points lower than those without (P < .01). A subset of patients (n = 75) completed a second COST survey approximately 1 year later. Financial toxicity status was relatively stable; 67% (18/27) of patients experiencing it at baseline were still at the later time point and only 10% (5/48) of patients previously not experiencing financial toxicity were at the later time point.

Conclusion: Over one-third of patients with MM were considered to be experiencing financial toxicity and financial toxicity was associated with reduced satisfaction with MM treatment.

Introduction: Uptake of BCMA-directed antibody drug conjugates (ADCs) in multiple myeloma has been hindered by ocular side-effects. Belantamab mafodotin (BelMaf) and MEDI2228 are BCMA-directed monoclonal-antibodies conjugated to the microtubule inhibitor, monomethyl auristatin F and the alkylator, pyrrolobenzodiazepine, respectively. Differences in ADC payload, antibody specificity and linker stability influence ocular toxicity.

Aim/methods: We investigated the tolerability and ocular toxicity profiles of BCMA-directed ADC therapy. Retrospective study of 111 patients treated with BCMA-directed ADCs between 2019 and 2022.

Results: Eighty-seven percent of patients were triple-class refractory, 50% penta-class refractory, 14% had prior BCMA-directed therapy and 24% extraosseous disease. Treatments included BelMaf monotherapy (n = 56), BelMaf combination therapy (n = 12) and MEDI2228 monotherapy (n = 43). The overall response rate was 30% for BelMaf and 44% for MEDI2228. Photophobia was more common with MEDI2228 (any-grade: 12% vs. 49%, P < .001), whereas keratopathy was more common with BelMaf (any-grade: 59% vs. 9%, P = .002). Four MEDI2228 recipients developed keratopathy, all grade 1 and associated with dry eyes and/or photophobia. Dose delay for ocular toxicity was comparable for BelMaf and MEDI2228 (28% vs. 19%, P = 0.2), as was the rate of dose reduction (18% vs. 12%, P = .4). The most common reasons for treatment discontinuation were progression/death (BelMaf = 71%, MEDI2228 = 44%) and ocular toxicity (BelMaf = 18%, MEDI2228 = 30%).

Conclusions: Treatment interruptions, dose reductions and drug discontinuation are common with BCMA-directed ADC therapy. Research to optimize the administration schedule of these agents is warranted. BelMaf and MEDI2228 produce distinct patterns of ocular side-effects, namely keratopathy and reduced visual-acuity with the former, and photophobia and dry eyes with the latter.