Clinical Lymphoma, Myeloma & Leukemia最新文献

Background: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) relapse is the most frequent cause of allogeneic stem cell transplantation (allo-SCT) failure. The utility of post-relapse therapy is controversial due to the high incidence of toxicity and the low efficacy.

Methods: This sub-analysis of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) AML/MDS relapse study focuses on 647 AML/MDS relapsing after allo-SCT performed between 2015 and 2021. Following the relapse, these patients were treated with either hypomethylating agents (HMAs)-based therapy (n = 308) or other treatments (n = 339), including intensive chemotherapy, FLT3-inhibitors, and second allo-SCT.

Results: HMAs-based therapies were more frequently used in older patients, transplanted not in CR following a reduced-intensity conditioning regimen. The overall response rate (ORR) with or without HMA-based salvage treatment was 33% and 40%, respectively (P = .006). The complete remission (CR) rate was 23% and 33% in the two groups, respectively (P < .001). The long-term OS and TRM of the two groups were superimposable. Independently from the type of salvage, an advantage in OS was observed when donor lymphocytes infusion (DLI) was included (P < .001). Relapse within 12 months after SCT, low disease burden at relapse, and the CR status at transplant confirmed their independent strong prognostic impact on both HMA and non-HMA-based group (HR 0.05, 0.44, and 0.49 and HR 0.19, 0.32, and 0.53, respectively).

Conclusions: Despite the lower ORR observed with HMA-based therapy, the long-term OS was comparable to that observed with other therapies. The immune control of the disease relapse with DLI is of benefit, independently from the salvage therapy. .

Background: Despite the introduction of novel antimyeloma therapies, Black and Hispanic individuals with multiple myeloma (MM) often experience worse survival outcomes than White counterparts, influenced not only by disease-related factors but by nonbiological factors such as social drivers of health (SDOH). We evaluated the impact of the Area Deprivation Index (ADI), a neighborhood-level SDOH measure, on survival in patients with MM receiving standardized, high-quality care.

Methods: We conducted a retrospective cohort study of 476 patients with newly diagnosed MM treated at The University of Texas MD Anderson Cancer Center from January 2010 to December 2017. Progression-free survival (PFS) and overall survival (OS) were the primary outcomes.

Results: Of the cohort, 27% self-identified as Black, 18% as Hispanic, and 55% as White; 54% were male. Black and Hispanic patients were younger at diagnosis (median age 58.3 years) compared to White patients (63.1 years). White patients resided in neighborhoods with lower mean ADI values (51.7 ± 23.3) than Black (61.2 ± 21.5) and Hispanic (63.7 ± 19.3) patients, indicating lower deprivation. Higher ADI correlated with more advanced disease stage but no other clinical features. PFS and OS did not differ significantly by ADI quartile or race/ethnicity groups. Survival outcomes remained consistent in both race/ethnicity- and ADI-stratified analyses.

Conclusions: Although Black and Hispanic patients lived in areas of greater deprivation, survival outcomes were comparable across ADI and racial/ethnic groups. These findings suggest that access to standardized, high-quality care may mitigate disparities in outcomes driven by SDOH. Replication in other care settings is warranted.

The therapeutic landscape of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) has rapidly evolved over the past decade with the introduction of multiple novel agents and the emergence of immunotherapies such as bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapies. As these therapies become integrated into routine clinical practice, current treatment approaches now increasingly rely on timing of relapse and patient-specific factors such as eligibility and access to CAR T-cell therapy. Consequently, treatment sequencing has become increasingly complex and now represents a major challenge in the management of R/R DLBCL. In this review, we summarize the pivotal clinical trials that have informed current treatment strategies and discuss evolving approaches to sequencing therapies in R/R DLBCL, with an aim of optimizing curative potential.

Objectives: To explore the efficacy and safety olverembatinib-based therapy in patients with transformed chronic myeloid leukemia in lymphoid blast phase (CML-LBP) or relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (R/R Ph+ ALL).

Methods: Data of patients with transformed CML-LBP or R/R Ph+ ALL receiving olverembatinib-based therapy from 24 academic centers in China were retrospectively interrogated. Cox regression model was utilized to identify covariates associated with survival.

Results: 75 patients with transformed CML-LBP (n = 26, 35%) and R/R Ph+ ALL (n = 49, 65%) were enrolled in this study. Median age was 51 years old (interquartile range [IQR], 40-57 years). With a median follow-up of 18 months (IQR, 11-27 months), excluding 1 patient with early death, 58 patients (78%) achieved complete remission/complete remission with incomplete hematologic recovery by 28 days. The 2-year probability of overall survival was 43% (95% Confidence Interval [CI], 29-56%) with median overall survival of 18 months (95% CI, 7-29 months). The therapy was well-tolerated. In multivariate analyses, higher hemoglobin concentration (Hazard ratio [HR] = 0.9 [0.7, 1.0], P = .049) and receiving a transplant (HR = 0.2 [0.1, 0.5], P = .001) were significantly-associated with better survival.

Conclusions: Olverembatinib-based therapy is effective and tolerable in patients with transformed CML-LBP and R/R Ph+ ALL.

Introduction: Improvements in splenomegaly, anemia, and overall survival (OS) are key considerations in the management of patients with myelofibrosis. In the phase III SIMPLIFY-1 trial (NCT01969838), momelotinib was noninferior to ruxolitinib for spleen volume reduction ≥ 35% (SVR35) and nominally superior for transfusion independence (TI) at week 24 in Janus kinase (JAK) inhibitor-naive patients. However, the relative impact of these endpoints on OS in anemic patients has not been described.

Materials and methods: The present post hoc analysis evaluated week 24 SVR35, TI, and dual responses (SVR35 + TI) in patients with baseline hemoglobin < 10 g/dL.

Results: SVR35 rates were similar overall with momelotinib versus ruxolitinib (27/86 [31%] vs. 31/94 [33%]), but higher with momelotinib in the baseline platelets < 200 × 10⁹/L subgroup (19/49 [39%] vs. 8/47 [17%]) and with ruxolitinib in the baseline platelets ≥ 200 × 10⁹/L subgroup (8/37 [22%] vs. 23/47 [49%]). Week 24 SVR35 + TI was also more common with momelotinib (23/86 [27%]) than with ruxolitinib (7/94 [7%]). Subsequent OS analysis focused on the momelotinib arm only, as the crossover trial design precluded analysis of long-term OS with ruxolitinib. OS was longer in patients who were transfusion independent and/or achieved SVR35 at week 24 versus those who met neither endpoint (TI alone: n = 17, hazard ratio [HR], 0.25 [95% CI, 0.09-0.70]; SVR35 + TI: n = 23, HR, 0.40 [95% CI, 0.18-0.87]).

Conclusion: These results highlight that both spleen- and anemia-related benefits of momelotinib correlate with improved OS, supporting prioritization of TI in anemic patients for optimal long-term outcomes, and suggest that momelotinib may be the preferred JAK inhibitor in anemic patients with platelets < 200 × 10⁹/L.

Background: The European LeukemiaNet (ELN) guidelines are widely used for risk stratification in acutemyeloid leukemia (AML), but validation in non Western patients remains limited.

Materials and method: This retrospective study of 227 newly diagnosed AML patients from the Kuwait Cancer Control Center assessed the 2022 and 2017 ELN risk classification systems and their impact on event-free survival (EFS) and overall survival (OS), add ressing the need for diverse population data in AML prognostication.

Results: Compared to ELN2017, ELN2022 reclassified 14% of patients. Outcomes were effectively discriminated by both ELN2017 (EFS C index 0.607, log rank P < .001; OS C index 0.591, P < 001) and ELN2022 (EFS C index 0.607, P < .001; OS C index 0.590, P < .001). Among 171 patients receiving intensive chemotherapy (IC), ELN2022 was even more discriminative (EFS C index 0.650; OS C index 0.637). Multivariable analyses confirm ELN2022 as an independent predictor of outcomes for the full cohort (EFS 2df Wald P < .001; OS P = .004) and IC subset (EFS P < .001; OS P = .001). Consistent with Western findings, neither ELN system was validated in our subgroup of 28 nonintensively treated patients (for ELN2022, adverse risk had the longest median EFS and OS).

Conclusion: ELN2022 was an independent predictor of survival in a Middle Eastern AML cohort, particularly for patients receiving IC, validating this prognostic tool in an understudied population.

Nodal PTCLs are a rare subset of non-Hodgkin lymphomas that are clinically and biologically heterogenous and have poor outcomes. There have been several attempts to improve upon existing frontline therapies, many of which have shown improvement or signals of improvement in outcomes, such as adding etoposide and brentuximab vedotin to CHOP-based chemotherapy, and consolidative autologous stem-cell transplant in first remission. Though there has some been some success, many studied regimens have either failed to improve outcomes and/or have increased toxicity. However, many of these studies have unveiled important findings regarding the underlying biology of PTCLs, thereby leading to the design of more precise and biology-driven clinical trials. Additionally, attempts are being made to better risk stratify patients and identify strategies to best monitor patients following frontline treatment. Though many studies are ongoing, at this time better treatment strategies for frontline PTCL are needed.