Expert Review of Hematology最新文献

Introduction: Acute myeloid leukemia (AML) is a complex and heterogeneous disease characterized by an aggressive clinical course and limited efficacious treatment options in the relapsed/refractory (R/R) setting. Chimeric antigen receptor (CAR)-modified T (CAR-T) cell immunotherapy is an investigational treatment strategy for R/R AML that has shown some promise. However, obstacles to successful CAR-T cell immunotherapy for AML remain.

Areas covered: In analyses of clinical trials of CAR-T cell therapy for R/R AML, complete responses without measurable residual disease have been reported, but the durability of those responses remains unclear. Significant barriers to successful CAR-T cell therapy in AML include the scarcity of suitable tumor-target antigens (TTA), inherent T cell functional deficits, and the immunoinhibitory and hostile tumor microenvironment (TME). This review will focus on these barriers to successful CAR-T cell therapy in AML, and discuss scientific advancements and evolving strategies to overcome them.

Expert opinion: Achieving durable remissions in R/R AML will likely require a multifaceted approach that integrates advancements in TTA selection, enhancement of the intrinsic quality of CAR-T cells, and development of strategies to overcome inhibitory mechanisms in the AML TME.

Introduction: In the last decade, BTK inhibitors and the BCL-2 inhibitor venetoclax have replaced immunochemotherapy in the treatment of CLL.

Areas covered: This review describes the use of BTK inhibitors and BCL2 inhibitors in the treatment of naive and relapsed or refractory CLL, with particular attention to the mechanisms of resistance. It also addresses the management of double-refractory patients, and the discovery of novel drugs. The corpus of papers was obtained by a search of the PubMed and Google Scholar databases for articles in English.

Expert opinion: Covalent BTK inhibitors and venetoclax are commonly recommended for previously-untreated and relapsed/refractory CLL. However, resistance to both drug classes can develop over time. As such, double-refractory patients are difficult to manage and novel approaches are urgently needed.

Background: To assess the effectiveness of the combination of dexamethasone, rituximab, and cyclosporine in treating adults with primary immune thrombocytopenia (ITP).

Research design and methods: This prospective study enrolled consecutive adult patients diagnosed with ITP at the 967th Hospital of the Chinese People's Liberation Army Joint Service Support Force Hospital between November 2019 and February 2023.

Results: Twenty-eight patients (13 males, median age 43.5 years) were included. All patients previously experienced ineffective or relapsed ITP, with a median disease duration of 26.5 (range, 7-72) months. At baseline, the median platelet (PLT) count was 13.5 × 10⁹/L (8.25-20 × 10⁹/L). Following treatment, the PLT counts were significantly increased at weeks 1, 3, and 4. The early response rates at weeks 1 and 4 were 82.1% (23/28 patients) and 71.4% (20/28 patients), respectively. The 1-, 3-, and 6-month response rates were 71.4% (20/28), 67.9% (19/28), and 75% (21/28). The treatment-free survival rates at 12 and 24 months were 82.35% (14/17) and 71.43% (10/14), respectively. Six patients experienced transient adverse reactions.

Conclusions: The combination of dexamethasone, rituximab, and cyclosporine may present a promising therapeutic option for patients with refractory ITP, with good tolerability and mild adverse reactions.

Introduction: JAK inhibitors (JAKi) have changed the treatment paradigm of myelofibrosis (MF). Currently, 4 JAKis are approved in the US as monotherapy (mono) to treat patients with MF. JAKis are also being studied in combination (combo) with novel agents. Herein, we review some of the key studies that evaluated JAKi as mono and combo in MF.

Areas covered: We performed a Pubmed search for 'JAK inhibitors' and 'myelofibrosis' from 1/2010 to 12/2023. For mono, we included only the unique phase II/III studies of the approved JAKi. Selective studies that evaluated JAKi in combo with the novel agents were also included.

Expert opinion: JAKis aim to provide clinical benefit to patients via spleen size reduction and MPN symptom improvement. In order to potentially increase clinical benefit for patients with MF, several novel agents are being partnered with ruxolitinib (RUX) with the ongoing hypothesis to augment greater measures of MF disease modification. The novel agents are either 'added-on' to RUX or as a combo in JAKi naïve patients. Also, the mutant-targeting era of therapies is now beginning with novel CALR-mutated, novel JAK2 V617F mutation-specific and type II JAK2i in the initial stages of drug development, representing a new approach to treatment.

Background: To explore the genetic causal association between lymphoma and the circulating levels of vitamins through Mendelian randomization (MR).

Research design and methods: We performed MR analysis using publicly available genome-wide association study (GWAS) summary data. Seven indicators related to the circulating levels of vitamins (vitamin D, vitamin C, vitamin B6, vitamin B12, folic acid, vitamin E, and carotene) served as exposures, while lymphoma was the outcome. The genetic causal association between these circulating levels of vitamin indicators and lymphoma was assessed using the inverse variance weighted (IVW) method.

Results: Based on IVW method, vitamin B12 (OR = 0.48; 95% CI: 0.28-5.19; p = 0.018) and folic acid (OR = 0.62; 95% CI: 0.40-0.96; p = 0.032) both showed substantial evidence of a relationship with lymphoma. Moreover, the Weighted median method similarly indicated potential evidence of an association between vitamin B12 (OR = 0.40; 95% CI: 0.18-0.90; p = 0.027) and lymphoma. The Simple mode, and Weighted mode methods showed no potential genetic causal association (p > 0.05 in the two analyses).

Conclusions: This study suggests a potential association between folic acid and vitamin B12 and lymphoma. Further research is required to assess the reproducibility of this finding in different contexts and to gain deeper insights into the potential underlying mechanisms.

Background: Preterm infants are a group cohort of transfusion recipients due to their low blood volume and underdeveloped hematopoietic system. The objective of this study was to probe the effect of days of age at first blood transfusion on intraventricular hemorrhage (IVH) in very low and extremely low birth weight VLBW and ELBW infants.

Research design and methods: Data of 150 VLBW and ELBW infants receiving blood transfusions were reviewed. IVH and non-IVH groups were established. General data on infants and their mothers and data related to blood transfusion, IVH risk factors, and the predictive value of the relevant factors for IVH were analyzed.

Results: The IVH group had lower birth weight, hemoglobin levels on admission, and days of age at first blood transfusion and higher 5-min Apgar score ≤7 points and early transfusion rate. Spontaneous delivery and 5-min Apgar score ≤7 points were risk factors for IVH. Birth weight and days of age at first blood transfusion had predictive value for IVH in VLBW and ELBW infants.

Conclusions: The younger the days of age at first blood transfusion, the higher the IVH risk. It is necessary to delay the days of age at first blood transfusion and reduce early blood transfusion.

Background: Multiple myeloma (MM) is a plasma cell neoplasm, which accounts for 1-2% of cancers and approximately 17% of hematological malignancies in the United States each year. Fifty percent of patients with symptomatic MM have three or more primary care visits before being referred to a specialist, which is greater than any other cancer. A delay in the diagnosis of multiple myeloma has been shown to negatively impact the clinical course of the disease; patients with longer diagnostic intervals have been shown to experience shorter disease-free survival and higher rates of treatment-related complications.

Research design and methods: We performed a retrospective analysis of patients diagnosed with MM in our institution, to determine the time from the first detectable lab abnormality to the diagnosis of MM.

Results: We included 92 patients in this study. Fifty-two percent of patients had isolated anemia at the time of diagnosis. Twenty-nine percent of patients had a delay in diagnosis of ≥1 year, while 18% had a delay of ≥3 years. Nine patients in our cohort had anemia and an elevated serum total protein (31%). This group had the longest time to diagnosis with a median of 38 months.

Conclusions: Our results did not show any difference in time to diagnosis by race, ethnicity, gender, or socioeconomic status.

Introduction: Acute promyelocytic leukemia (APL) is a distinct form of acute myeloid leukemia characterized by the presence of t(15;17)(q24;21) and the PML:RARA gene fusion. Frontline use of intravenous arsenic trioxide (i.v.-ATO) and all-trans retinoic acid (ATRA) has vastly improved cure rates in APL. Researchers in Hong Kong invented the oral formulation of ATO (oral-ATO) and have confirmed a bioavailability comparable to i.v.-ATO. A plethora of studies have confirmed the safety and efficacy of oral-ATO-based regimens in the frontline and relapsed setting.

Areas covered: Aspects on the development of oral-ATO-based regimens for APL in the frontline and relapsed setting are discussed. The short-term and long-term safety and efficacy of oral-ATO-based regimens are discussed. The frontline use of oral-ATO in combination with ATRA and ascorbic acid (AAA) induction in a 'chemotherapy-free' is highlighted.

Expert opinion: Current and ongoing data on the use of oral-ATO-based regimens in APL support the use of oral-ATO as an alternative to i.v.-ATO allowing a more convenient and economical approach to the management of APL.

Introduction: The improved quality of care and increased drug availability have shifted the goal of treating people with hemophilia from life-threatening bleeding prevention to joint health preservation and quality of life amelioration. Many tools are now available to the clinician in order to optimize the management of hemophilic arthropathy.

Areas covered: This paper reviews the pivotal role of ultrasound evaluation in early detection of joint bleeding and differential diagnosis of joint pain, with a focus on the feasibility of a long-term monitoring of joint health through the use of artificial intelligence and telemedicine. The literature search methodology included using keywords to search in PubMed and Google Scholar, and articles used were screened by the coauthors of this review.

Expert opinion: Joint ultrasound is a practical point-of-care tool with many advantages, including immediate correlation between imaging and clinical presentation, and dynamic evaluation of multiple joints. The potential of telemedicine care, coupled with a point-of-care detection device assisted by artificial intelligence, holds promises for even earlier diagnosis and treatment of joint bleeding. A multidisciplinary approach including early intervention by physical medicine and rehabilitation (PMR) physicians and physiotherapists is crucial to ensure the best possible quality of life for the patient.

Introduction: Mantle cell lymphoma (MCL) is an uncommon non-Hodgkin lymphoma that is generally considered incurable. Covalent BTK inhibitors (cBTKi) are the cornerstone of treatment for relapsed or refractory (R/R) MCL, but treatment options are limited and prognosis is poor after cBTKi failure. Pirtobrutinib is a non-covalent BTK inhibitor that has demonstrated excellent efficacy and safety and represents an important new treatment in the evolving treatment landscape of R/R MCL.

Areas covered: This review will provide an overview of the therapeutic landscape of R/R MCL, characteristics of pirtobrutinib, and efficacy and safety data of pirtobrutinib in R/R MCL from pivotal clinical trials. PubMed and major hematology conference proceedings were searched to identify relevant studies involving pirtobrutinib.

Expert opinion: For patients with R/R MCL that has progressed after treatment with cBTKi, pirtobrutinib is an important and efficacious treatment that confers favorable outcomes. In the post-cBTKi setting, when chimeric antigen receptor (CAR) T-cell therapy is not available or feasible, pirtobrutinib is the preferred treatment for R/R MCL. How to sequence or combine pirtobrutinib with CAR T-cell therapy and other available or emerging therapies requires further investigation. Future studies should also explore the role of pirtobrutinib in earlier lines of therapy for MCL.