Vaccination in Multiple Myeloma: Challenges and Strategies.

Background: Multiple myeloma (MM) is a hematological malignancy characterized by profound immunosuppression resulting from both disease-related mechanisms and treatment-induced immune dysfunction. This compromised immune status markedly increases susceptibility to infections, a leading cause of morbidity and mortality in MM patients. While vaccination represents a cornerstone of infection prevention, standard immunization strategies often yield suboptimal responses in this population.

Maintenance therapy after ASCT in newly diagnosed multiple myeloma patients: single agent combination drugs.

Introduction: Maintenance therapy plays a crucial role in prolonging progression-free survival and overall survival in multiple myeloma. Lenalidomide remains the gold standard, as demonstrated in phase 3 trials, consistently showing superior survival compared to observation or placebo. However, both established and novel agents - such as thalidomide and pomalidomide, proteasome inhibitors (PIs), monoclonal antibodies (moAbs), and bispecific antibodies - have been investigated as alternatives to assess their efficacy and safety.

Treatment-Free Remission in Chronic Myeloid Leukemia: Revisiting the "W" Questions.

Chronic myeloid leukemia (CML) has undergone a transformation from a fatal disease to a chronic, manageable condition with the advent of tyrosine kinase inhibitors (TKIs), particularly imatinib. This shift has significantly improved survival rates, and for some patients, achieving deep molecular response (DMR) has made treatment-free remission (TFR) a feasible goal. However, the ability to sustain TFR remains a challenge, primarily due to the persistence of leukemia stem cells (LSCs), which are inherently resistant to TKIs and contribute to relapse after treatment cessation.

TP53-Mutated Acute Myeloid Leukemia: Unanswered Questions.

TP53-mutated acute myeloid leukemia (AML) remains one of the most treatment-resistant hematologic malignancies, with poor overall survival despite advancements in therapeutic strategies. The loss of functional p53 compromises DNA repair, apoptosis, and genomic stability, rendering both conventional and novel therapies largely ineffective. This review evaluates the efficacy of various treatment approaches, including intensive chemotherapy (IC), hypomethylating agents (HMAs), venetoclax-based regimens, and immune checkpoint inhibitors.

Rilzabrutinib for the Treatment of Immune Thrombocytopenia.

Advancements in the understanding of ITP pathogenesis have led to significant improvements in disease management through the use of both traditional immunosuppressive strategies and novel targeted therapies. However, a subset of patients remains refractory to treatment or achieves only transient benefits, underscoring the need for alternative therapeutic approaches. Bruton's tyrosine kinase (BTK) inhibitors have emerged as a promising strategy for autoimmune cytopenias, including ITP, due to their ability to modulate key immune pathways.

Dosing and clinical outcomes of ruxolitinib in patients with myelofibrosis in a real-world setting: Interim results of the Italian observational study (ROMEI).

Background: Myelofibrosis (MF) significantly impacts patients' overall survival (OS) and quality of life (QOL). This prospective study analyzed ruxolitinib dosing patterns and associated clinical outcomes in patients with MF over 12 months.

Methods: ROMEI, a multicenter, observational, ongoing study, enrolled 508 adult patients with MF treated with ruxolitinib.

Frailty predicts treatment-related toxicity and discontinuation in older adults with chronic lymphocytic leukemia treated with BTK and BCL-2 inhibitors: Findings from a prospective single-center cohort study.

Introduction: Chronic lymphocytic leukemia (CLL) particularly impacts older adults with multiple comorbidities. The advent of targeted therapies has improved outcomes, but challenges related to treatment adherence and drug interactions persist. Assessment of frailty is recommended to tailor treatment, though its application in clinical settings is often limited due to its complexity.

Therapeutic Strategies for Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia in Adult Patients: Optimizing the Use of Monoclonal Antibodies.

The treatment landscape for relapsed or refractory acute lymphoblastic leukemia (RR ALL) has evolved significantly with the introduction of monoclonal antibodies such as blinatumomab and inotuzumab ozogamicin. These agents have demonstrated remarkable efficacy, achieving high response rates and minimal residual disease (MRD) negativity. However, the optimal selection, sequencing, and integration of monoclonal antibodies and other modalities like standard chemotherapy or chimeric antigen receptor T-cell therapy remain areas of active investigation.

Relapsed/Refractory Follicular Lymphoma: Current Advances and Emerging Perspectives.

Follicular lymphoma (FL) is a prevalent indolent non-Hodgkin lymphoma (NHL) characterized by a relapsing course and eventual refractoriness to therapy. Despite advancements in treatment, FL remains incurable, necessitating ongoing research into novel therapeutic strategies. This review provides a comprehensive overview of current standard treatments for relapsed or refractory (R/R) FL, including chemoimmunotherapy and stem cell transplantation, and delves into emerging therapies such as chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies.

Avatrombopag for the Treatment of Immune Thrombocytopenia.

Avatrombopag, a second-generation thrombopoietin receptor agonist (TPO-RA), represents a significant advancement in the treatment of chronic immune thrombocytopenic purpura (cITP) and a potential therapeutic option for other thrombocytopenic disorders. Approved in both the USA and Europe, avatrombopag offers a convenient oral dosing regimen, initiated at 20 mg daily with food, to achieve and maintain platelet counts ≥ 50 × 10/L. Its favorable safety profile, characterized by minimal hepatic toxicity and the absence of dietary restrictions, distinguishes it from older TPO-RAs such as eltrombopag and romiplostim.

Advances and Challenges in Quizartinib-Based FLT3 Inhibition for Acute Myeloid Leukemia: Mechanisms of Resistance and Prospective Combination Therapies.

FLT3 mutations are among the most common genetic alterations in acute myeloid leukemia (AML) and are associated with poor prognosis. Significant advancements have been made in developing FLT3 inhibitors (FLT3Is), such as quizartinib, which have improved treatment outcomes in both newly diagnosed and relapsed/refractory AML. Resistance to FLT3Is remains a major clinical challenge, driven by diverse mechanisms including FLT3 point mutations, cellular escape pathways, and the influence of the bone marrow microenvironment.

Talquetamab in Multiple Myeloma: Efficacy, Safety, and Future Directions.

Relapsed and refractory multiple myeloma (RRMM) remains a challenging condition despite advances in immunotherapies. Novel bispecific antibodies (BsAbs), including talquetamab, have shown promising efficacy in heavily pretreated patients, even those with triple- and penta-refractory disease. Talquetamab, recently approved by the FDA and EMA, is indicated for patients who have progressed after at least three or four prior lines of therapy (LOTs).

Mosunetuzumab for the treatment of follicular lymphoma.

Introduction: Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma that shows a progressive increase in relapses and refractory in its natural history and a median survival of approximately 18-20 years. The advent of anti-CD20 monoclonal antibodies has changed the FL therapeutic algorithm, with an increase in progression-free survival. T-cell-dependent bispecific antibodies (BsAbs) represent an emerging drug class against FL.

Investigational CXCR4 inhibitors in early phase development for the treatment of hematological malignancies.

Introduction: CXCR4/CXCL12 axis regulates cell proliferation, survival, and differentiation, as well as the homing and mobilization of hematopoietic stem cells (HSCs) from bone marrow niches to the peripheral blood. Furthermore, CXCR4 and CXCL12 are key mediators of cross-talk between hematological malignancies and their microenvironments. CXCR4 overexpression drives disease progression, boosts tumor cell survival, and promotes chemoresistance, leading to poor prognosis.

Selinexor in multiple myeloma.

Introduction: Selinexor, an XPO1 inhibitor, has emerged as a promising therapeutic option in the challenging landscape of relapsed/refractory multiple myeloma (RRMM).

Areas Covered: This article provides a review of selinexor, with a focus on available clinical studies involving MM patients and its safety profile. Clinical trials, such as STORM and BOSTON, have demonstrated its efficacy, particularly in combination regimens, showcasing notable overall response rates (ORR) and prolonged median progressionfree survival (mPFS).

Ivosidenib in acute myeloid leukemia.

Introduction: Traditional treatment strategies for acute myeloid leukemia (AML) have primarily relied on standard chemotherapy regimens for four decades. Indeed, the landscape of AML therapy has evolved substantially in recent years, mainly due to the introduction of hypomethylating agents and small molecules.Bcl2 inhibitor venetoclax, Fms-like tyrosine kinase 3 (FLT3) inhibitors such as midostaurin and gilteritinib, and isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) inhibitors ivosidenib and enasidenib, as well as hedgehog (HH) pathway inhibitor glasdegib represented a significant step forward in AML therapeutic armamentarium.

Teclistamab-cqyv in multiple myeloma.

Multiple myeloma (MM) is an incurable neoplasm characterized by significant morbidity and mortality. Despite advances in treatment, MM patients eventually experienced a relapse of the disease. Penta-drug refractory patients continue to be the hard core of relapsed/refractory (RR) settings.

Tagraxofusp in myeloid malignancies.

Tagraxofusp (or SL-401) is a recombinant molecule composed of human interleukin-3 that binds CD123 on neoplastic cells fused to a truncated diphtheria toxin (DT). Tagraxofusp's most significant success has come from studies involving patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive disease that is usually refractory to conventional chemotherapy. Tagraxofusp had an acceptable safety profile and high efficacy in early phase I/II studies on patients with BPDCN.