Introduction: In this era of information explosion, how can one quickly access the latest developments in the field? Here, we select the latest literature in the field every month, focusing on hot topics, comprehensively interpreting new advances in hematologic diseases, and helping you stay at the forefront of the disease field. Let's track the latest trends together, gain insights into research trends, and explore the boundless possibilities in the world of hematology! Stay tuned every month for the latest updates!01
Significance of Measurable Residual Disease in Adult Philadelphia Chromosome-Positive ALL: A GRAAPH-2014 Study
- Journal: J Clin Oncol. 2024 Jul 19: JCO2400272.
- DOI: 10.1200/JCO.24.00272.
- Impact Factor: 42.1
- Authors: Rathana Kim, PharmD, PhD, et al.
Recent studies indicate that BCR::ABL1 may affect multiple hematopoietic lineages in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL), potentially influencing clinical treatment strategies. This study explores the prognostic significance of BCR::ABL1 and IG/TR as measurable residual disease (MRD). In the GRAAPH-2014 trial, 264 Ph+ALL patients underwent nilotinib therapy and hematopoietic stem cell transplantation (HSCT), with MRD monitoring.
The study found that 43% of patients exhibited characteristics of multi-lineage Ph+ALL, where BCR::ABL1 and IG/TR levels were inconsistent. Despite higher neutrophil counts in multi-lineage Ph+ALL patients, their disease-free survival (DFS) and overall survival (OS) were similar to those with primitive lymphoid Ph+ALL. IG/TR MRD levels were significantly associated with lower DFS after the second treatment cycle, and patients who did not achieve molecular remission of IG/TR before transplantation had a higher risk of DFS events. BCR::ABL1 MRD status did not significantly affect DFS before transplantation.
The conclusion indicates that IG/TR MRD is an important indicator for predicting survival and allo-HSCT benefit in Ph+ALL patients. White blood cell count (WBC) and IG/TR MRD levels independently predict DFS, aiding in identifying patients likely to benefit from intensified therapy. These findings support the use of IG/TR MRD as a key tool in Ph+ALL treatment decisions.
02
Efficacy of CAR T-cell Therapy is not Impaired by Previous Bispecific Antibody Treatment in Large B-cell Lymphoma
- Journal: Blood
- DOI: 10.1182/blood.2024024526.
- Impact Factor: 25.669
- Authors: Gilles Crochet et al.
This retrospective study evaluates the effectiveness and safety of chimeric antigen receptor T-cell therapy (CAR-T) in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL), particularly those previously treated with bispecific antibodies (BsAbs). The study included 47 patients who received CD19-targeted CAR-T therapy between 2018 and 2023, excluding those previously treated with CD19/CD3 BsAbs.
Baseline characteristics showed a median age of 65 years among patients, mostly in stage III or IV, predominantly with non-specified large B-cell lymphoma. Objective response rates (ORR) were 46% and complete response rates (CRR) were 19% with a progression-free survival (PFS) of 3.1 months following prior BsAbs treatment.
Results of CAR-T therapy showed an optimal ORR of 85% and CRR of 43%, unaffected by previous response status to BsAbs. Median follow-up was 10.5 months, with a median PFS of 6.6 months, 1-year PFS rate of 42%, and 1-year overall survival (OS) rate of 55%. Propensity score matching (PSM) analysis showed that patients previously treated with BsAbs demonstrated a higher ORR compared to those not receiving BsAbs, with no significant statistical differences in CRR, 1-year PFS, or 1-year OS.
Regarding safety, 57% of patients experienced cytokine release syndrome (CRS) during BsAbs treatment, while 79% experienced CRS post CAR-T therapy (6% grade 3 or higher), and 23% experienced immune effector cell-associated neurotoxicity syndrome (ICANS, 2% grade 3 or higher).
03
Low Dose Lenalidomide versus Placebo in Non-Transfusion Dependent Patients with Low Risk, del(5q) Myelodysplastic Syndromes (SintraREV): A Randomised, Double-Blind, Phase 3 Trial
- Journal: Lancet Haematol
- DOI: 10.1016/S2352-3026(24)00142-X
- Impact Factor: 15.4
- Authors: María Díez-Campelo et al.
This randomized, double-blind, multicenter phase 3 clinical trial aimed to evaluate the efficacy and safety of low-dose lenalidomide in non-transfusion-dependent patients with low or intermediate-1 risk del(5q) myelodysplastic syndromes (MDS). The study included 61 adult patients from 22 study centers, who were not transfusion-dependent and had an ECOG score of ≤2. Patients were randomized in a 2:1 ratio to receive either 5 mg of lenalidomide daily or placebo for 2 years.
The primary endpoint of the study was time to transfusion dependence from the start of treatment. Secondary endpoints included erythroid and cytogenetic responses, time to transfusion independence, changes in hemoglobin, platelets, and neutrophils, overall survival (OS), event-free survival (EFS), and safety assessment.
At baseline, the median age of patients was 72.2 years, predominantly female, and most patients belonged to the low-risk group according to IPSS. 89% of patients had isolated del(5q) abnormality, while 11% had del(5q) combined with other cytogenetic changes. After a median follow-up of 60.6 months, the median time to transfusion dependence was not reached in the lenalidomide group, compared to 11.6 months in the placebo group, indicating a significant reduction in the risk of transfusion dependence with lenalidomide.
Regarding secondary endpoints, 70% of patients in the lenalidomide group achieved erythroid response, and 80% achieved cytogenetic response, with 70% achieving complete response. Additionally, median hemoglobin levels increased by 2.7 g/dL at the end of lenalidomide treatment, and EFS was significantly superior to the placebo group. There were no significant differences between the two groups in terms of PFS and OS.
Safety data showed that neutropenia was more common in the lenalidomide group, but mostly mild. Non-hematologic toxicities mainly included skin disorders, constipation, and abdominal discomfort. Most severe adverse events occurred in the lenalidomide group, but no treatment-related deaths were reported. Despite a higher incidence of second cancers in the lenalidomide group, researchers concluded that it did not significantly increase patient risk.
In summary, low-dose lenalidomide demonstrated significant efficacy in prolonging time to transfusion dependence, improving erythroid and cytogenetic responses, enhancing hemoglobin levels, and extending EFS in specific del(5q) MDS patients, with manageable safety. This provides compelling evidence for early anemia treatment in these patients, potentially improving their disease outcomes and quality of life.
