Clinical Lymphoma, Myeloma & Leukemia最新文献

Background: Multiple myeloma (MM) is a hematologic malignancy defined by clonal proliferation of plasma cells in the bone marrow. The introduction of bortezomib, a proteasome inhibitor, has significantly improved outcomes in MM, becoming a cornerstone of therapy since its approvals for relapsed/refractory MM in 2003 and newly diagnosed MM (NDMM) in 2008. Bortezomib induces apoptosis in malignant plasma cells by disrupting protein degradation pathways.

Rationale: Triplet regimens combining bortezomib with immunomodulatory drugs, alkylating agents, and corticosteroids have shown high efficacy, especially in NDMM patients ineligible for autologous stem cell transplant (ASCT). However, clinical trials often underrepresent real-world populations, with 40% to 50% of MM patients not meeting eligibility criteria.

Methods: To address this evidence gap, we performed a retrospective analysis of national real-world data from the Czech Republic, assessing 17 years of experience with bortezomib-based triplet regimens in transplant-ineligible NDMM patients.

Conclusions: This study provides critical insights into the long-term effectiveness and applicability of bortezomib-based therapies outside of controlled trial settings, offering a more comprehensive understanding of treatment outcomes in routine clinical practice.

Background: In multiple myeloma, ¹⁸F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) positivity after first-line autologous stem cell transplantation (ASCT) is associated with reduced progression-free survival (PFS) and overall survival (OS). Intensified treatment may abrogate the adverse effects of a positive PET after ASCT, but this treatment strategy has not been evaluated in prospective clinical trials.

Patients and methods: In this phase II clinical study, patients who were in at least very good partial response (VGPR) after ASCT and had a positive PET received four cycles of KRd treatment. These patients were compared with patients in at least VGPR after ASCT that were PET negative and received standard post-ASCT treatment. Bone-marrow based minimal residual disease (MRD) assessment at a sensitivity of 10^-5 was performed before and after treatment in the PET positive patients.

Results: After a median follow-up of 53 months, PFS was similar between PET positive patients who received KRd and PET negative patients who received standard of care (median 65.3 months vs. median 51.3 months, P = .610). Median OS was not reached in either group. MRD status after KRd treatment was significantly associated with PFS and OS, and patients who were both MRD and PET positive after KRd treatment had poor prognosis.

Conclusion: Long-term outcomes were similar between PET positive patients who received KRd consolidation therapy and PET negative patients who received standard post-ASCT therapy. Newer treatment strategies are needed for patients who are both PET/CT and MRD positive after intensified consolidation therapy.

Background: ETV6:RUNX1 has a good prognosis in pediatric acute lymphoblastic leukemia (ALL). However, it shows a controversial prognostic pattern due to the increased risk of late relapses. We aimed to analyze the clinico-laboratory features and treatment outcomes of patients with ETV6::RUNX1.

Methods: This study involved newly diagnosed precursor B-ALL pediatric patients who had the ETV6::RUNX1 fusion gene between January-2016 and December-2022, in the National Cancer Institute (NCI), Cairo University.

Results: Out of 645, 111 (17.2%) tested positive for ETV6::RUNX1. The mean age was 5.2 years (SD ± 2.9). Conventional cytogenetic analysis revealed that 54.2% (39/71) had concurrent chromosomal aberrations. Younger age (< 10 years) and initial leukocyte count ≤ 50,000/µl were associated with better remission outcomes (P < .001 and P = .03, respectively). Overall survival (OS) was significantly affected by the remission status on day 15 (P = .001) and disease risk (P = .006). Additionally, disease-free survival (DFS) was negatively impacted by splenomegaly (P = .042), the immunophenotyping of c-ALL (P = .01), and the presence of aberrant myeloid markers (P = .001). Twelve patients (10.8%) experienced relapses. The 5-year estimated cumulative incidence of relapse (CIR) was significantly lower for hypodiploidy and high hyperdiploidy when compared to the modal chromosomal number (MCN) of 47 to 50 chromosomes (0%, 0% vs. 21%, P < .001). Multivariate analysis identified the initial platelet count < 40 × 10³/mL as an adverse independent prognostic factor impacting the OS.

Conclusions: The treatment protocols need to be tailored based on further refine the stratification of ETV6::RUNX1 patients. Platelet count is an adverse independent prognostic factor. Splenomegaly and aberrant CD33 expression are associated with shorter DFS.

Background: Salvage autologous stem cell transplantation (ASCT2) remains a treatment option for selected patients with relapsed multiple myeloma (MM). In this multicenter study, we conducted a retrospective analysis using the Canadian Myeloma Research Group (CMRG) database to evaluate real-world outcomes of ASCT2 in the maintenance era.

Patients and methods: Three hundred and fifty-two patients underwent ASCT2 following progression after ASCT1 between 2012 and 2021. Progression-free survival (PFS), overall survival (OS), depth of response, and the impact of maintenance therapy after ASCT2 were assessed, with further stratification based on maintenance use after ASCT1.

Results: Our analysis demonstrated that post-ASCT2 maintenance therapy was associated with improved outcomes, particularly in patients who had also received maintenance after ASCT1 (25.2 months (95% CI, 20.8-39.6) versus 11.6 months (95% CI, 8.51-18.8)). In patients receiving lenalidomide maintenance after ASCT1, a remission lasting less than 3 years represented a high risk group with poor outcomes with an ASCT2.

Conclusion: While novel agents continue to expand treatment options, ASCT2 remains a viable therapeutic strategy in appropriately selected patients, especially those with durable responses to prior therapy.

Background: Achievement of complete remission (CR) has long been one of the goals of acute myeloid leukemia (AML) treatment. Less stringent criteria for defining CR (sub-CR) have been developed to facilitate clinical trials and regulatory approvals. However, the clinical value of sub-CR in the context of advancements in sequencing and measurable residual disease, and non-intensive therapy is incompletely understood.

Methods: We performed a retrospective analysis of 363 patients with AML (2019-2023) with CR or sub-CR responses. The primary objective was to determine predictors of sub-CR response.

Results: CR was achieved in 227 and sub-CR in 136 patients. Receiving non-intensive chemotherapy (OR 8.80; 95% [4.25-18.20], P < .001) and having spliceosome pathway mutations (OR 3.53; [1.45-8.57], P = .005) were independent predictors for sub-CR response. Consistent with prior studies, patients achieving a sub-CR response following intensive chemotherapy had inferior survival compared to those achieving CR (median OS: not reached (CR) vs. 26 months [18-NA] (sub-CR); P = .002). On MVA, older age (HR 1.75; [1.04-2.95], P = .034) and adverse ELN risk (HR 2.55; [1.53-4.23], P = .001) was associated with inferior OS. But sub-CR response (HR 1.45; [0.91-2.33], P = .119) was not associated with inferior OS. In patients who received non-intensive treatment, there was no significant difference in EFS or OS between the CR and sub-CR populations.

Conclusions: In patients treated with intensive chemotherapy, achieving a sub-CR response appears to be reflective of poor disease biology. Whereas, in patients treated with non-intensive therapies, sub-CR responses may result from the continuous nature of the treatment and not necessarily portend an inferior outcome. The potential role of spliceosome pathway variants should be further evaluated.

Acute lymphoblastic leukemia (ALL) incidence in Mexico and Central America is among the highest worldwide, with a significant proportion of cases occurring in adolescents and young adults (AYA). Historically, outcomes for Mexican adults with ALL have been poor, driven by high treatment-related mortality, limited access to specialized care and diagnostics, and a higher prevalence of adverse-risk genetic subtypes, including Philadelphia-like ALL. During the last decade, pediatric-inspired regimens (PIR) have transformed the management of AYA ALL globally, but their implementation in low- and middle-income countries poses unique challenges. We describe the adaptation and stepwise implementation of a modified CALGB 10403 (mCALGB) regimen in Mexico, replacing pegaspargase with native E. coli asparaginase and standardizing supportive care. Across six centers in Mexico and Guatemala, 95 patients treated with mCALGB achieved a complete remission rate of 87.8%, 2-year overall survival (OS) of 72.1%, and relapse rate of 28.3%, markedly improved compared with historical Mexican cohorts and approaching outcomes of the original CALGB 10403 trial. Similar results have been reproduced by other Latin American groups using BFM- or CALGB-based regimens. Key challenges remain, including higher rates of induction infections, metabolic toxicities linked to obesity and Hispanic ancestry, and major disparities in access to diagnostics and novel agents such as blinatumomab and CAR-T cells. Future priorities include national strategies to expand precision diagnostics, collaborative clinical research, and equitable implementation of innovative therapies. Pediatric-inspired regimens adapted to local resources represent a critical step toward closing the survival gap for Hispanic AYA patients with ALL.

Background and aims: Nucleophosmin (NPM1) mutations are associated with favorable outcomes in adults; however, their prognostic relevance in pediatric acute myeloid leukemia (AML) remains unclear due to their rarity. This single center study from India, investigates the prevalence and prognostic impact of NPM1-mutated childhood AML.

Methods: Patients less than 15 years of age with newly diagnosed AML treated between January 2016 and December 2023 were included. NPM1 and FLT3 mutations were detected via multiplex PCR or next generation sequencing (NGS). Treatment consisted of standard 3 + 7 induction followed by 3 cycles of high-dose cytarabine and 1 year of oral maintenance. FLT3-ITD positive patients also received sorafenib or midostaurin.

Results: Of the 552 patients enrolled, 35 (6.3%) had NPM1 mutation. Patients with NPM1- mutations had higher median age (9 vs. 8 years; P = .05) and a greater frequency of FLT3/ITD co-mutations (40% vs. 11%; P < .001). Among the 32 NPM1-mutated patients who underwent NGS, type A (59%) was the most common. While complete remission rates and measurable residual disease negativity were comparable, NPM1-mutated patients demonstrated significantly better 3-year event-free survival (52.1% vs. 26%; P = .001) and overall survival (56.3% vs. 27.8%; P = .004). Although FLT3-ITD status was independently prognostic, it did not influence survival within the NPM1-mutated subgroup. Patients with a VAF < 39% had a better 3-year EFS (73.5% vs. 40.4%; P = .35).

Conclusions: Our study confirms NPM1 mutations independently predict improved survival in pediatric AML, though outcomes remain inferior to those reported from high income countries. Larger studies are needed in pediatric AML due to its rare occurrence.

Objectives: This study compared patient and disease-related demographics, access to treatment, and the OS of Australian and New Zealand (ANZ) patients with multiple myeloma.

Study design: A retrospective cohort study of ANZ patients with a new diagnosis of (MM) enrolled between 2012 and 2023 onto the bi-national Myeloma and Related Diseases Registry (MRDR). Baseline characteristics (age, gender, country), clinical data (ISS Stage, comorbidities, high-risk cytogenetics, performance status), and OS from date of diagnosis to all-cause mortality were used to compare the two cohorts. The Cox proportional hazard model was applied to covariates to analyse the association with survival. All data analysis was performed with R.

Results: A total of 5031 patients were included in this study (3871 from Australia and 1160 from New Zealand). Patients in New Zealand demonstrated an older median age, more cardiac disease and poorer performance status (ECOG 2-4) at diagnosis, but the two cohorts were otherwise similar. New Zealand patients had a significantly inferior median OS when compared to Australian patients, 65.3 vs. 79.8 months, respectively. Adjusted for demographic and clinical characteristics, utilization of autologous stem cell transplant (ASCT, HR 0.59, 95% CI, 0.51-0.68), frontline combination therapy with a proteasome inhibitor and an IMID combination (HR 0.63, 95% CI, 0.55-0.72), and receiving anti-CD38 monoclonal antibody therapy at first relapse compared with VTD regimen (HR 0.61, 95% CI, 0.44-0.83) were associated with improved survivals. New Zealand patients were less frequently transplanted across all age groups after adjusting for cofounders.

Conclusion: Despite both countries having access to publicly funded health care, the survival for patients with newly diagnosed MM in New Zealand is significantly inferior when compared to Australian counterparts.

Objective: The CARTITUDE-1 Trial (C-1) led to the approval of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR-T cell therapy, for patients with relapsed or refractory multiple myeloma (RRMM) after ≥ 3 lines of therapy. However, the inclusion criteria may not fully represent patients in the real-world (RW).

Methods: Leveraging a national multicenter cohort of patients with RRMM, we conducted a retrospective analysis comparing 73 patients who received cilta-cel in the RW to 97 patients treated in C-1 by evaluating clinical characteristics, depth of response, survival outcomes, and toxicity.

Results: Results showed that the RW baseline demographics such as age, proportion of racial minorities, gender, prior therapies, and disease characteristics, including high-risk cytogenetics, were broadly similar to the C-1 population. In the RW group, fewer patients had Eastern Cooperative Oncology Group 0 (16% vs. 40%, P < .001), more patients had extramedullary disease (29% vs. 13%, P = .02), and fewer were refractory to bortezomib (47% vs. 68%, P = .007) and anti-CD38 monoclonal antibody (88% vs. 97%, P = .03). Forty-five percent of RW patients did not meet the inclusion criteria for C-1. The overall response rate was lower in the RW group (88% vs. 97%, P = .015). The survival outcomes at 24-months including the progression-free survival (58% in RW vs. 62% in C1, P = .98) and overall survival (72% vs. 74%, P = .9) were similar. The safety profile of RW patients was better with fewer treatment-related adverse events.

Conclusion: Our study demonstrates the comparable efficacy of cilta-cel in patients with RRMM treated in a RW setting.