Clinical Lymphoma, Myeloma & Leukemia最新文献

Immunotherapy has transformed the treatment of acute lymphoblastic leukemia (ALL) over the past 2 decades with excellent outcomes in both adults and children particularly in the relapsed/refractory (R/R) disease setting where in general the treatment outcomes are dismal. Several immune therapies including monoclonal antibodies, bispecific T cell engagers, antibody-drug conjugates, and chimeric antigen receptor T-cells have shown excellent outcomes and safety in this setting. Based on the observed high response rates and improved survival outcomes in patients with R/R ALL, immunotherapy is now being prospectively studied in the upfront setting with an aim to reduce treatment related toxicity and death with conventional chemotherapy. In this manuscript we discuss the various clinical trials that have shown excellent outcomes in the frontline setting and discuss how best to incorporate them in newly diagnosed, treatment naïve ALL patients either as monotherapy or in combination with cytotoxic agents.

Background: While the distribution of frailty status in patients with multiple myeloma (MM) has been documented at a single time point, there is limited data examining how frailty changes over time in this population.

Patients and methods: Patients aged > 18 years initiating treatment for newly diagnosed or relapsed MM between Aug 2021 and Jul 2023 across 3 sites in Ontario, Canada were enrolled. Frailty assessments were conducted at two time points (baseline and 12-months) using 4 frailty categorization tools: 1) the IMWG frailty index, 2) the Simplified frailty index, 3) the Mayo frailty index, and 4) the Fried frailty phenotype. At baseline and the 12-month follow-up, the frequency and proportion of patients were calculated for both frailty categorization (i.e., non-frail, frail) and continuous frailty scores (i.e., scores 0-5).

Results: A total of 116 patients with newly diagnosed or relapsed MM were evaluated for frailty assessments at baseline and after a 12-month follow-up, using 4 different frailty indices. Changes in frailty status across the cohort varied from 13.8% to 37.1%, due to differences in how frailty was defined between each frailty index. In comparison, changes in continuous frailty score across the cohort varied from 20.7% to 51.7%. A total of 17.2% of patients experienced a reduction in gait speed of at least 0.1 m/s.

Conclusion: This study demonstrates the dynamic nature of frailty highlighting that a one-time baseline frailty measurement may not be adequate. Additionally, continuous frailty scores may be more sensitive to early improvements/deteriorations in frailty that may go undetected using categorical frailty assessments.

Background: Waldenström macroglobulinemia (WM) is a rare, indolent lymphoma, and death from non-WM causes has become increasingly important in treatment decisions. This study explored the causes of death in WM patients.

Methods: The data from 8894 patients diagnosed with WM in the Surveillance, Epidemiology, and End Results (SEER) database from 1980 to 2016 were included. Standardized mortality ratios (SMRs) were used to assess the relative risk of death compared with that of the general US population.

Results: Considering other competing events, the 5-year cumulative incidences of death from the index cancer, SMNs and noncancer causes were 8.6% (SD: 1.00e-05), 10.02% (SD: 1.17e-05) and 16.14% (SD: 1.79e-05), respectively, among WM patients. WM patients had the highest SMR for index cancer-related death, at 121.84 (95% CI, 103.8-142.11) in the first year after diagnosis, which declined thereafter. Among nonindex cancer-related deaths, hematological malignancy-related deaths were notably increased, whereas solid neoplasm deaths were elevated only 10 years after diagnosis (SMR, 1.43; 95% CI, 1.06-1.9). Among noncancer causes of death, infection, particularly among patients <50 years old, had the highest SMR (SMR, 19.01; 95% CI, 10.12-32.5). There were decreasing trends in the SMRs of index cancer-related deaths, all nonindex cancer-related deaths and many noncancer disease-related deaths from 1980 to 2001 and 2002 to 2016.

Conclusions: Currently, the risk of noncancer-related deaths (mainly cardiovascular disease-related deaths) exceeds that of cancer-related deaths among WM patients. These findings may provide improved guidance regarding future health risks for WM patients.

T-cell non-Hodgkin lymphomas (NHL) are a heterogenous group of malignancies that represent a minority of all NHL cases world-wide. Outcomes with traditional chemotherapy-based regimens remain poor with notably dismal outcomes in the relapsed/refractory setting. The power of immunotherapy has revolutionized treatments and outcomes for hematologic malignancies and has already made significant strides in addressing the treatment needs in T-cell NHLs. Given the heterogeneity of T-cell lymphoma subtypes and biology, a wide variety of innovative immunotherapies have been evolving to treat these various malignancies. Here, we review the promising advancement of various immunotherapies in T-cell NHLs including antibody-based therapies targeting T-cell surface antigens and checkpoint signaling, as well as the expanding strategies for chimeric antigen receptor T-cell (CAR-T) therapy in this difficult to treat disease space.

We retrospectively analysed cytogenetics by fluorescence in situ hybridization (FISH) in 1.026 patients with multiple myeloma treated in real-world with the aim to establish its role in daily clinical practice. Thirty-seven percent of patients had no FISH data available. Based on median PFS of each cytogenetic abnormality found, we identified 3 group of patients with a significantly different PFS and determined which patients can best benefit from anti-CD38 regimens and double transplant. These findings support cytogenetic testing in all patients at diagnosis.

Background: Cytogenetics by fluorescence in situ hybridization (FISH) plays an increasing prognostic role in multiple myeloma (MM).

Methods: we analysed cytogenetics and its implications in 1.026 patients treated in real-world from 2019 to 2023. Low-risk (LR) patients had normal cytogenetic or del(13q); intermediate-risk (IR) had t(11;14), hyperdiploidy, gain(1q) or del(1p); high-risk (HR) group had del(17p)/TP53, amp1q21, t(4;14), t(14:16) or t(14;20). Co-existence of 2 high risk abnormalities was named double hit.

Results: FISH data were not evaluable in 383 patients (37%). Out of 643 evaluable patients, chromosome 1 alterations were observed in 119 (18.5%), high risk chromosome 14 translocations in 65 (10%), del(17p)/TP53 in 37 (6%) and double-hit in 7 patients (1%). Cytogenetic was normal or hyperdiploid in 252 (39%) and 59 (13%) patients, respectively. Median PFS of LR, IR and HR group were 57.5, 43.2 and 30.5 months, respectively (P < .001). Although anti-CD38 regimens resulted in significantly longer PFS in both TE and NTE pts, in the former significant benefit was documented in the LR and IR group but not in HR group while in the latter only in the LR group. Tandem transplantation did not improve PFS both overall and in the 3 risk groups. Multivariate Cox regression analysis selected ECOG-PS ≥2, R-ISS II-III and our cytogenetic score HR as factors affecting PFS.

Conclusions: in real world, more than one third of MM patients do not have baseline FISH data. Nevertheless, cytogenetics and ECOG PS can be used for prognostic staging and for tailoring therapy.

Background: The International prognostic index (IPI) is a widely used model for identifying trial-eligible patients with diffuse large B-cell lymphoma (DLBCL). However, the applicability of prognostic models in identifying trial-eligible high-intermediate (HI) and high-risk (H), particularly younger patients, has not been extensively studied.

Methods: Patients with newly diagnosed DLBCL were identified in the Danish Lymphoma Registry (LYFO). To evaluate the impact of IPI and age-adjusted IPI (aaIPI) on identifying higher-risk (HI and H-risk) trial-eligible patients, we retrieved the eligibility criteria for the frontMIND trial (NCT04824092).

Results: Of 6252 patients with DLBCL registered in the LYFO, 3725 (59.6%) were trial-eligible. The dataset included all IPI/aaIPI groups. However, 46% of 3725 patients would meet trial eligibility if IPI and aaIPI higher-risk patients were selected. The 5-year progression-free (PFS) and overall survival (OS) were 61.7% and 70.5%, respectively. Among patients aged ≤ 60 years (35.5%; 1321/3725), 29.5% were frontMIND-eligible based on aaIPI, with 5-year PFS and OS of 72.3% and 82.8%, respectively. Combining IPI and aaIPI did not improve the identification of patients who did not respond to standard treatment, and utilizing this strategy for trial selection was not superior to using IPI or NCCN-IPI alone.

Conclusions: Prognostic models can help in selecting trial-eligible HI and H-risk patients, thereby increasing the chances of identifying those who do not respond to standard treatment. However, the currently used prognostic indices fail to accurately recognize some high-risk patients, particularly young patients. Therefore, additional risk factors beyond prognostic models are needed to improve patient selection for trial participation.

Purpose: Guidelines from the American Society for Transplantation and Cellular Therapy (ASTCT) propose use of the Immune Effector Cell-Associated Encephalopathy (ICE) score as a means by which to grade Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). However, ICE scoring may not appropriately capture ICANS among patients with limited English proficiency or diverse educational or cultural backgrounds. With the development of protocols for early ICANS treatment and the advent of CAR-T repurposing for solid tumors, creation of an accessible neurotoxicity grading framework (and an accurate clinical correlate) for all patients is paramount.

Methods: Using a quantitative and qualitative descriptive study design, we surveyed staff members at a United States safety-net hospital experienced in grading the ICE score. We then performed an iterative thematic analysis of data embedded within free-text responses and used a modified version of the theoretical framework of acceptability (TFA) to guide evaluation of the anticipated intervention.

Results: Of the 36 survey respondents, most (27/36, 75%) agreed that lack of language concordance could lead to inaccurate ICE scores. While translation services were thought to be used appropriately (33/36, 92%), logistical barriers including availability of interpreter services (in-person, phone, tablet) were thought to impact quality of care for non-native English-speaking patients. Additional barriers to accurate ICE scoring included patient literacy, numeracy (eg, cultural differences in measuring time), education level, or disability status (eg, hearing or vision loss, memory or cognitive impairment).

Conclusion: This needs assessment demonstrated stakeholder perspectives on the standard ICE score; associated challenges among patients with limited English proficiency and illiteracy; and the utility of an alternative language-concordant and culturally humble grading system for neurotoxicity among non-native English speakers.

Background: Ponatinib, a third-generation tyrosine kinase inhibitor, has demonstrated its activity against chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). However, real-world data, particularly in Asian populations, remain limited.

Methods: Patients with CML or Ph+ ALL treated with ponatinib in Taiwan between March 2013 and November 2024 were retrospectively collected. Molecular and cytogenetic data, efficacy outcomes (complete hematologic response [CHR], molecular response [MR], progression-free survival [PFS], overall survival [OS]), and adverse events were analyzed.

Results: Among 52 patients (27 CML and 25 Ph+ ALL; median follow-up: 50.7 months), 94% received ponatinib due to relapsed or refractory disease. Among patients without prior CHR, 89% reached CHR at 12 months. Among patients without prior MR, 57% had MR2.0, 53% MR3.0, and 26% MR5.0 at 12 months. MR2.0 at 6 months and MR3.0 at 12 months correlated with improved outcome in patients with CML. Additional chromosomal abnormalities (ACAs) were identified in 36% of patients and were associated with inferior survival, whereas kinase domain mutations in 78% of studied patients, including T315I (57%), did not affect the outcome. MR3.0 at any time predicted superior OS and PFS in patients with CML, and MR5.0 with superior PFS in patients with Ph+ ALL. One patient (1.9%) had an arterial occlusive event.

Conclusion: Ponatinib demonstrated substantial real-world efficacy in pretreated patients with CML and Ph+ ALL, with MR3.0 in CML and MR5.0 in Ph+ ALL emerging as favorable prognostic markers. In contrast, the presence of ACAs was associated with shorter survival.