Blood and Lymphatic Cancer-Targets and Therapy最新文献

Despite recent advancements in treatments, including proteasome inhibitors, immunomodulators, and anti-CD38 monoclonal antibodies, multiple myeloma (MM) remains mostly incurable with patients frequently experiencing disease relapses due to therapy resistance. Hence there is an urgent need for innovative treatments for patients with relapsed and/or refractory MM (RRMM). This review examines Belantamab mafodotin, the first antibody-drug conjugate (ADC) targeting B-cell maturation antigen (BCMA), which has shown efficacy in pre-clinical and clinical settings for RRMM. BCMA, a type III transmembrane glycoprotein critical for B cell functions, is predominantly expressed in malignant plasma cells making it a promising therapeutic target. ADCs, comprising a monoclonal antibody, a cytotoxic payload, and a linker, offer a targeted and potent therapeutic approach to cancer treatment. Belantamab mafodotin integrates an afucosylated monoclonal antibody and monomethyl auristatin F (MMAF) as its cytotoxic agent. It induces apoptosis in MM cells by disrupting microtubule formation and interfering with important signaling pathways. The series of DREAMM (Driving Excellence in Approaches to MM) studies have extensively evaluated Belantamab mafodotin in various clinical settings. This review provides a comprehensive overview of pre-clinical and clinical data supporting Belantamab mafodotin as a future therapeutic option for RRMM.

Background: The aim of the study was to evaluate the efficacy and safety of induction and consolidation with all-trans retinoic acid (ATRA) +arsenic trioxide (ATO) +anthracyclines and maintenance with ATRA +Realgar-Indigo naturalis formula (RIF) for high-risk APL.

Methods: Twenty-one patients with high-risk APL treated with ATRA+ATO+ anthracyclines for induction and consolidation and ATRA+RIF for maintenance from 2012 to 2021 were analyzed. Endpoints include morphological complete remission (CR) and complete molecular remission (CMR), early death (ED) and relapse, survival and adverse events (AEs).

Results: After induction treatment, all 21 patients (100%) achieved morphological CR and 14 people (66.7%) achieved CMR. Five of the 21 patients did not undergo immunological minimal residual disease (MRD) examination after induction; however, 14 of the remaining 16 patients were MRD negative (87.5%). The median time to achieve CR and CMR was 26 days (range: 16-44) and 40 days (range: 22-75), respectively. The cumulative probability of achieving CR and CMR in 45 days was 100% and 76.2% (95% CI: 56.9-91.3%), respectively. All patients achieved CMR and MRD negativity after the three courses of consolidation treatment. The median follow-up was 66 months (25-142), with no central nervous system relapse and bone marrow morphological or molecular relapse until now, and all patients survived with 100% overall survival and 100% event-free survival. Grade 4 adverse events (AEs) were observed in 3 patients (14.3%) during the induction period including arrhythmia (n = 1), pulmonary infection (n = 1) and respiratory failure (n = 1); and the most frequent grade 3 AEs were pulmonary infection, accounting for 62.0% and 28.6%, respectively, during induction and consolidation treatment, followed by neutropenia, accounting for 42.9% and 38.1%, respectively.

Conclusion: For newly diagnosed high-risk APL patients, induction and consolidation with ATRA+ATO+anthracyclines and maintenance with ATRA+RIF is a highly curative treatment approach.

Background: The albumin-to-globulin ratio (AGR) and neutrophil-to-lymphocyte ratio (NLR) have been recently regarded as promising prognostic factors in various malignancies. The present study investigated the prognostic value of combining the AGR and NLR (ANS) for risk assessments in multiple myeloma (MM) with renal impairment (RI).

Methods: From 2011 to 2018, 79 patients with MM and RI were enrolled in this study. Receiver operating curves (ROCs) were constructed to determine optimal AGR and NLR thresholds for predicting overall survival (OS) and progression-free survival (PFS) during follow up. The prognostic values of AGR, NLR, and ANS were evaluated with Cox regression and Kaplan-Meier methods. We also created a predictive nomogram for prognostic evaluations of OS and PFS, and the predictive accuracy was assessed with a concordance index (c-index).

Results: The ROC curves analyses showed that the optimal cut-off levels were 2.27 for NLR and 1.57 for AGR. A high NLR and a high ANS were significantly associated with worse OS and PFS. However, a high NLR combined with a low AGR was associated with worse OS. Multivariate analyses demonstrated that both the NLR and ANS were independent predictors for both OS and PFS and that a low AGR was an independent predictor of a reduced OS. The nomogram accurately predicted OS (c-index: 0.785) and PFS (c-index: 0.786) in patients with MM and RI.

Conclusion: ANS may serve as a potential prognostic biomarker in patients with MM and RI. The proposed nomograms may facilitate prognostic predictions for patients with MM and RI.

Despite excellent results in frontline therapy, particularly in pediatric age, refractory Burkitt lymphoma still remains a therapeutic challenge, with dismal outcome. The prognosis is very poor, ranging from less than 10% to 30-40%, with longer survival only in transplanted patients. On account of the paucity of data, mostly reporting on small series of patients, with heterogeneous characteristics and salvage treatments, at present it is impossible to draw definitive conclusions on the treatment of choice for this difficult to treat subset of patients. New insights into Burkitt lymphoma/leukemia cell biology have led to the development of new drugs, currently being tested, directed at different specific targets. Herein, we describe the results so far reported in refractory Burkitt lymphoma/leukemia, with standard treatments and hematopoietic stem cell transplant, and we review the new targeted drugs currently under evaluation.

Polycythemia vera (PV) is a subtype of myeloproliferative neoplasms characterized by impaired quality of life and severe complications. Despite the increasingly in-depth knowledge of this condition, it necessitates a multifaceted management approach to mitigate symptoms and prevent thrombotic and hemorrhagic events, ensuring prolonged survival. The therapeutic landscape has been revolutionized in recent years, where venesection and hydroxycarbamide associated with antiplatelet therapy have a central role and are now accompanied by other drugs, such as interferon and Janus kinase inhibitors. Ongoing research and advancements in targeted therapies hold promise for further enhancing the therapeutic choice for PV management.

Purpose: The pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of zanbrutinib are described.

Summary: Mantle cell lymphoma (MCL) is a mature B-cell lymphoma that is typically associated with unfavorable outcomes, and virtually all patients with MCL have refractory or relapsed disease despite aggressive treatment. The treatment paradigm for MCL has transformed dramatically over the past decade owing to rapid advancements in immunotherapy and molecular-targeted therapies. Zanubrutinib, a second-generation Bruton's tyrosine kinase inhibitor (BTKI) designated for mature B-cell non-Hodgkin's lymphoma (NHL), has drastically improved the survival outcomes in relapsed/refractory (R/R) MCL patients. This selective BTKI is a small molecule that functions by forming a covalent bond in the active site of BTK. The inhibition of BTK activity is essential for the signaling of B-cell antigen receptor (BCR) and cytokine receptor pathways. In a preclinical study, zanubrutinib inhibited malignant B-cell proliferation and reduced tumor growth. Zanubrutinib was granted FDA-accelerated approval based on the results of Phase I and II trials. The investigator-assessed overall response rate was 83.7%, of which 78% of patients achieved complete response. The median duration of response was 19.5 months, and the median progression-free survival was 22.1 months. The most common (≥20%) all-grade adverse events were low neutrophil count (46.5%), upper respiratory tract infection (38.4%), rash (36.0%), low white blood cell count (33.7%), and low platelet count (32.6%).

Conclusion: Zanubrutinib is a selective, next-generation, orally active, irreversible BTK inhibitor. The selectivity of zanubrutinib and its superior efficacy, with a well-tolerated safety profile, have proven to be attractive options for other malignancies.

Radioimmunotherapy (RIT) with radio-labeled monoclonal antibodies to CD20 produces a high response rate in patients with low-grade B-cell lymphomas. The use of this modality in patients with chronic lymphocytic leukemia (CLL) has been sporadic in clinical trials and was hampered by the extensive marrow involvement seen commonly in patients with CLL, which would produce a high risk for marrow aplasia after treatment with RIT. Herein, we report our experience with RIT in 5 patients with CLL or SLL showing short-lived responses and significant myelosuppression. After 90Y-ibritumomab tiuxetan treatment, the median time to relapse was 65 days, and no cases of MDS or AML were observed during follow-up. All patients experienced grade ≥3 thrombocytopenia and neutropenia, with median durations of 39.5 days and 107 days, respectively.

Multiple myeloma (MM) is a hematologic malignancy characterized by the abnormal clonal proliferation of plasma cells that may result in focal bone lesions, renal failure, anemia, and/or hypercalcemia. Recently, the diagnosis and treatment of MM have evolved due to a better understanding of disease pathophysiology, improved risk stratification, and new treatments. The incorporation of new drugs, including proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies and high-dose chemotherapy followed by hematopoietic stem cell transplantation, has resulted in a significant improvement in patient outcomes and QoL. In this review, we summarize differential diagnoses and therapeutic advances in MM.

Human immunodeficiency virus infection is related with an increased risk of hematological malignancy principally, non-Hodgkin lymphoma. Most non-Hodgkin lymphomas are acquired immunodeficiency syndrome defining and constitute greater than 50% of all acquired immunodeficiency syndrome defining cancers. The main pathogenesis mechanisms are immunodeficiency, chronic antigenic stimulation, and the ability to infect cancer cells causing direct carcinogenesis. Human immunodeficiency virus related non-Hodgkin lymphomas are heterogeneous in immunophenotyping and molecular features; and choice of drug treatments is similar with sporadic types. The main objective is to assess the epidemiology, pathogenesis, and morphology of human immunodeficiency virus related non-Hodgkin lymphoma. The searching strategy was done by searching relevant original and review articles from www.biosemanticjane/org, Google scholar, Google, and PubMed sites using keywords like; Acquired immunodeficiency syndrome, Human immunodeficiency virus, and non-Hodgkin lymphoma. In conclusion, human immunodeficiency virus infected people continue to have elevated risk of non-Hodgkin lymphoma. Diffuse large B-cell lymphomas are the most common and severe subtype. The pathogenesis of this type of lymphoma is associated with chromosomal abnormalities that deregulate the expression of various oncogenes by different viral particles and cytokines. However, the role of these viral particles and cytokines on pathogenesis is not clearly stated, so further study could be required.

Primary pituitary diffuse large B-cell lymphoma (PPL) has been regarded as a subtype of primary central nervous system lymphoma (PCNSL); however, the pituitary gland is located outside the blood brain barrier (BBB) with neural and vascular connections to the brain. Given its unique anatomic location, a combination of non-central nervous system (CNS)-penetrating and CNS-penetrating therapeutic agents can be employed to treat PPL. We report a female patient with PPL who was successfully managed with anatomy-adapted therapy incorporating non-CNS penetrating chemoimmunotherapy [rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)] alternating with CNS-penetrating chemoimmunotherapy [rituximab, high-dose methotrexate, and high-dose cytarabine (RMA)]. She received a total of eight cycles of treatment with four cycles of each regimen following partial transsphenoidal resection. She achieved a complete response after two cycles and has remained in complete remission for the last eight years. To our knowledge, this is the longest documented survival in a patient with PPL. Targeted genomic profiling with Next-Generation Sequencing (NGS) was recently performed on the lymphoma tissue. The genomic profile of PPL in this patient is quite different from the findings typically associated with PCNSL. We suggest that PPL may be biologically distinct from PCNSL and should be treated with an anatomy adapted approach. Additional research is necessary to confirm our findings.