Impact of minimal residual disease response and of status of disease on survival after blinatumomab in B-cell acute lymphoblastic leukemia: results from a real-life study.

Blinatumomab is a bispecific T-cell engager approved for relapsed/refractory and minimal residual disease positive B-cell Acute Lymphoblastic Leukemia. We conducted a retrospective study evaluating the outcome of Blinatumomab. The impact of clinical and treatment-related variables on cumulative incidence of relapse/progression (CIRP), event-free (EFS) and overall survival (OS) was analyzed. From January 2016 to December 2022 50 Ph'- (37) and Ph+ (13) B-ALL patients received Blinatumomab. The median age was 37. Indications to blinatumomab were relapsed/refractory B-ALL in 29 and MRD-positive in 21 patients. Blinatumomab was the 2nd and 3rd line in 40 and in 10 patients, respectively. Twenty patients were treated pre-transplantation, ten were treated for relapse after transplant, twenty were not eligible for transplant. Out of 29 patients treated for relapsed/refractory disease, 16 (55%) achieved complete response and 12 achieved MRD-negativity. Out of 21 patients treated for MRD, 16 (76%) achieved MRD-negativity. At a median follow-up of 46 months the median EFS and OS were 11.5 and 16.2 months. The CIRP was 50%. In univariate analysis age, disease-status (overt vs. minimal disease) at blinatumomab, bridging to transplant after blinatumomab and MRD-response resulted significant for EFS and OS. In multivariate analysis only disease-status and MRD-response retained significance both for EFS and OS. Disease-status and MRD-response resulted significant for EFS and OS also after censoring at HSCT. This retrospective study on B-ALL patients treated with blinatumomab confirms a superior outcome for MRD-responsive over MRD non-responsive patients. Survival depends also on the disease-status prior treatment.

Gaucher disease prevalence in 600 patients affected by monoclonal gammopathy of undetermined significance.

BACKGROUND: Gaucher disease (GD) is a rare autosomal recessive inherited disorder caused by the lysosomal enzyme acid ß-glucosidase deficiency. Many patients experience a critical delay in the diagnosis of up to 8-10 years due to its rarity and variability in signs and symptoms, with the consultation of several specialists. PATIENTS AND METHODS: This prospective observational study analyzed the prevalence of GD in 600 patients with monoclonal gammopathy of uncertain significance (MGUS) from January 2018 until February 2022. RESULTS: The mean age of participants was 66 years, with a mean monoclonal component of 0.58 g/dL. In 433 MGUS patients with available data, anemia (hemoglobin level < 10 g/dL) was present in 31 patients (7%), and thrombocytopenia (platelet count <100.000/mm3 ) in 24 (5.5%). Of 600 MGUS patients tested for acid ß-glucosidase enzyme activity, 7 patients (1.2%) had activity below 2.5 nmol/h/mL. In comparison, GBA gene analysis was executed in 110 patients. It revealed 4 patients (0.7%) affected by GD (3 patients with compound heterozygous mutation and 1 with homozygous mutation), with a prevalence of 1 every 150 MGUS patients. Furthermore, 12 out of the remaining 106 evaluated patients (11%) were carriers of a single heterozygous mutation while having regular enzyme activity. CONCLUSIONS: The clinical heterogeneity of GD and frequent lack of awareness among physicians often lead to diagnostic delays and severe clinical manifestations. The role of MGUS in the presence of at least one clinical sign, such as low platelet count, organomegaly, bone pain, or bleeding tendency, could aid in initiating GD screening with DBS, thus reducing the period between symptom onset and the diagnosis of this rare disease.

GIMEMA AML1310 trial of risk-adapted, MRD-directed therapy for young adults with newly diagnosed acute myeloid leukemia.

We designed a trial in which postremission therapy of young patients with de novo acute myeloid leukemia (AML) was decided combining cytogenetics/genetics and postconsolidation levels of minimal residual disease (MRD). After induction and consolidation, favorable-risk patients (FR) were to receive autologous stem cell transplant (AuSCT) and poor-risk patients (PR) allogeneic stem cell transplant (AlloSCT). Intermediate-risk patients (IR) were to receive AuSCT or AlloSCT depending on the postconsolidation levels of MRD. Three hundred sixty-one of 500 patients (72%) achieved a complete remission, 342/361 completed the consolidation phase and were treatment allocated: 165 (48%) to AlloSCT (122 PR, 43 IR MRD-positive) plus 23 rescued after salvage therapy, for a total of 188 candidates; 150 (44%) to AuSCT (115 FR, 35 IR MRD-negative) plus 27 IR patients (8%) with no leukemia-associated phenotype, for a total of 177 candidates. Overall, 110/177 (62%) and 130/188 (71%) AuSCT or AlloSCT candidates received it, respectively. Two-year overall (OS) and disease-free survival (DFS) of the whole series was 56% and 54%, respectively. Two-year OS and DFS were 74% and 61% in the FR category, 42% and 45% in the PR category, 79% and 61% in the IR MRD-negative category, and 70% and 67% in the IR MRD-positive category. In conclusion, AuSCT may still have a role in FR and IR MRD-negative categories. In the IR MRD-positive category, AlloSCT prolongs OS and DFS to equal those of the FR category. Using all the available sources of stem cells, AlloSCT was delivered to 71% of the candidates.This trial was registered at www.clinicaltrials.gov as #NCT01452646 and EudraCT as #2010-023809-36.

Tailoring haemophilia A prophylaxis with BAY 81-8973: A case series.

BAY 81-8973 is an unmodified, full-length third generation recombinant factor VIII (rFVIII) which offers a more favorable pharmacokinetic (PK) profile, compared to its predecessor sucrose-formulated rFVIII (rFVIII-FS). We here report on a retrospective case series of nine patients affected by hemophilia A (HA), with variable disease severity, bleeding phenotype and comorbidities, to underline our clinical practice on prophylaxis with a recently introduced standard hall-life recombinant Factor VIII. The current case series highlights how the current clinical management of hemophilia is able to personalize treatment in several specific conditions like concomitant illnesses with thrombotic risk and allergic reactions.

Donor-Specific Anti-HLA Antibodies in Haploidentical Stem Cell Transplantation with Post-Transplantation Cyclophosphamide: Risk of Graft Failure, Poor Graft Function, and Impact on Outcomes.

The presence of donor-specific anti-HLA antibodies (DSA) is associated with a 10-fold increased risk of graft failure in haploidentical stem cell transplantation (haplo-SCT). Consensus guidelines from the European Society for Blood and Marrow Transplantation set a mean fluorescence intensity (MFI) >1000 as a cutoff for DSA positivity. In the absence of an alternative donor, it is recommended that patients undergo desensitization therapy, especially with high DSA levels (>5000 MFI). The aim of this study was to analyze the impact of DSA on risk of graft failure and poor graft function, as well as on major outcomes in a consecutive cohort of patients who were systematically screened for DSA before haplo-SCT. A total of 141 consecutive patients were candidates for unmanipulated haplo-SCT with post-transplantation cyclophosphamide (PT-Cy) at our center between January 2012 and January 2018, and 135 were analyzed for the presence of HLA antibodies. Of these 134 patients underwent haplo-SCT. HLA antibodies were detected in 40 patients, including 19 with DSA and 21 without DSA. Ten of the 19 patients with DSA underwent transplantation using that donor, whereas 2 underwent a desensitization program before transplantation. Only 2 patients experienced primary graft failure (1.4 %), both of whom were without DSA. Twenty patients developed a poor graft function (15%). The 3-year overall survival (OS), 3-year progression-free survival (PFS), and 1-year nonrelapse mortality (NRM) were analyzed according to the presence or absence of DSA. No statistically significant difference was found. No impact of the presence of DSA on the risk of developing graft failure and poor graft function was revealed. Major outcomes of transplantation were analyzed separately in patients with poor graft function and those with good graft function. The 3-year OS, 3-year PFS, and 1-year NRM in good graft function and poor graft function populations were 62% versus 20% (P < .0001), 53% versus 20% (P < .0001), and 12% versus 40% (P = .009), respectively. The presence of low-level DSA in the absence of desensitization did not correlate with the risk of developing graft failure and poor graft function. Patients who experienced poor graft function had worse outcomes than patients with good graft function.

Prognostic implications of additional genomic lesions in adult Philadelphia chromosome-positive acute lymphoblastic leukemia.

To shed light onto the molecular basis of Philadelphia chromosome-positive acute lymphoblastic leukemia and to investigate the prognostic role of additional genomic lesions, we analyzed copy number aberrations using the Cytoscan HD Array in 116 newly diagnosed adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia enrolled in four different GIMEMA protocols, all based on a chemotherapy-free induction strategy. This analysis showed that patients with Philadelphia chromosome-positive acute lymphoblastic leukemia carry an average of 7.8 lesions/case, with deletions outnumbering gains (88% versus 12%). The most common deletions were those targeting IKZF1, PAX5 and CDKN2A/B, which were detected in 84%, 36% and 32% of cases, respectively. Patients carrying simultaneous deletions of IKZF1 plus CDKN2A/B and/or PAX5 had a significantly lower disease-free survival rate (24.9% versus 43.3%; P=0.026). The only IKZF1 isoform affecting prognosis was the dominant negative one (P=0.003). Analysis of copy number aberrations showed that 18% of patients harbored MEF2C deletions, which were of two types, differing in size: the longer deletions were associated with the achievement of a complete molecular remission (P=0.05) and had a favorable impact on disease-free survival (64.3% versus 32.1% at 36 months; P=0.031). These findings retained statistical significance also in multivariate analysis (P=0.057). KRAS deletions, detected in 6% of cases, were associated with the achievement of a complete molecular remission (P=0.009). These results indicate that in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia a detailed evaluation of additional deletions - including CDKN2A/B, PAX5, IKZF1, MEF2C and KRAS - has prognostic implications and should be incorporated in the design of more personalized treatment strategies.

Long-Term Molecular Remission Achieved by Antibody Anti-CD22 and Ponatinib in a Patient Affected by Ph'+ Acute Lymphoblastic Leukemia Relapsed after Second Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report.

Ph'+ acute lymphoblastic leukemia (Ph'+-ALL) is an oncohematologic disorder for which allogeneic bone marrow transplantation still offers the only chance of cure. However, relapse is the main reason for treatment failure, also after hematopoietic stem cell transplantation (HSCT). New drugs, such as third generation tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, have expanded the therapeutic landscape, especially in patients who relapsed before HSCT. Very few reports, up to now, have described the use of both classes of these new agents in combination with donor lymphocyte infusions (DLI) in the setting of patients who relapsed after HSCT. We report on a young patient affected by Ph'+-ALL, who relapsed after the second HSCT and who reached molecular remission and long-term disease control by treatment with the anti-CD22 monoclonal antibody inotuzumab ozogamicin, DLI, and the 3rd generation TKI ponatinib.

Pomalidomide experience: an effective therapeutic approach with immunomodulatory drugs in a patient with relapsed-refractory multiple myeloma.

Here we discuss the case of a heavily pretreated male patient with relapsed-refractory multiple myeloma and previous monoclonal gammopathy of undetermined significance who initiated a fifth-line treatment with pomalidomide (4 mg orally, days 1-21 of a 28-day cycle) and low-dose dexamethasone (40 mg weekly orally). A total of 3 months later, very good partial response was achieved and complete response was maintained for 7 months. This case illustrates the field-practice experience on the benefits of pomalidomide in a relapsed-refractory multiple myeloma patient with a previous history of monoclonal gammopathy of undetermined significance. Indeed, the pomalidomide/dexamethasone regimen resulted in a longer progression-free survival compared with previous regimens and demonstrated a good long-term tolerability.

Allogeneic Stem Cell Transplantation in Refractory Acute Myeloid Leukaemia.

Refractory acute myeloid leukaemia is very difficult to treat and represents an unmet clinical need. In recent years, new drugs and combinations of drugs have been tested in this category, with encouraging results. However, all treated patients relapsed and died from the disease. The only curative option is allogeneic transplantation through a graft from a healthy donor immune system. Using myeloablative conditioning regimens, the median overall survival regimens is 19%. Several so-called sequential induction chemotherapies followed by allogeneic transplantation conditioned by reduced intensity regimens have been developed, improving the overall survival to 25-57%. In the allogeneic transplantation field, continuous improvements in practices, particularly regarding graft versus host disease prevention, infection prevention, and treatment, have allowed us to observe improvements in survival rates. This is true mainly for patients in complete remission before transplantation and less so for refractory patients. However, full myeloablative regimens are toxic and carry a high risk of treatment-related mortality. In this review, we describe the results obtained with the different modalities used in more recent retrospective and prospective studies. Based on these findings, we speculate how allogeneic stem cell transplantation could be modified to maximise its therapeutic effect on refractory acute myeloid leukaemia.

Sorafenib maintenance after allogeneic stem cell transplantation in patients with FLT3+ AML receiving midostaurin during induction and consolidation: a retrospective analysis.

Introduction: Acute myeloid leukemia (AML) relapse is the main cause of death after allogeneic stem cell transplant (allo-SCT). In AML FLT3+, it was shown that Sorafenib used as maintenance therapy after allo-SCT, significantly reduces the risk of relapse and death. Methods: We analyzed 29 adult patients with FLT3m AML and underwent allogeneic stem cell transplant from 2019 to 2023. All patients received midostaurin plus conventional CT during induction and consolidation. After transplantation, Sorafenib maintenance was administered in all patients independently from MRD status at transplantation. Results: Sorafenib maintenance was applied in 18 patients out 29 patients (62%). Median time to start sorafenib was 100 days (range 37-225) and median duration of treatment was 775 days (range 140-1064). For the whole population (n=29), 2-year OS, LFS, and CIR was 76%, 68% and 28%, respectively. The median time to relapse was 137 days (range 49-246). For patients treated with sorafenib (n=18), the 2-year OS, LFS, and CIR were 94%, 84% and 11%, respectively. For the whole population, the 100-day NRM was 0% and 1-year NRM was 3%. Death was caused by transplant-associated thrombotic microangiopathy in 1 patient. For patients who were administered with Sorafenib, the 1-y NRM was 5%. Death was caused by transplant associated transplant-associated thrombotic microangiopathy. Discussion: This retrospective study suggests that sorafenib maintenance seem to be effective even in patients pre-treated with midostaurin.

Glucosylsphingosine (Lyso-Gb1) as a reliable biomarker in Gaucher disease: a narrative review.

BACKGROUND: Gaucher disease (GD) is a rare, inherited, autosomal recessive disorder caused by a deficiency of the lysosomal enzyme, acid ß-glucosidase. Its diagnosis is achieved via measurements of acid ß-glucosidase activity in either fresh peripheral blood leukocytes or dried blood spots, and confirmed by identifying characteristic mutations in the GBA1 gene. Currently, several biomarkers are available for disease monitoring. Chitotriosidase has been used over the last 20 years to assess the severity of GD, but lacks specificity in GD patients. Conversely, the deacylated form of glucosylceramide, glucosylsphingosine (also known as lyso-Gb1), represents a more reliable biomarker characterized by its high sensitivity and specificity in GD. MAIN TEXT: Herein, we review the current literature on lyso-Gb1 and describe evidence supporting its usefulness as a biomarker for diagnosing and evaluating disease severity in GD and monitoring treatment efficacy. CONCLUSION: Lyso-Gb1 is the most promising biomarker of GD, as demonstrated by its reliability in reflecting disease burden and monitoring treatment response. Furthermore, lyso-Gb1 may play an important role in the onset of monoclonal gammopathy of uncertain significance, multiple myeloma, and Parkinson's disease in GD patients.

Effectiveness and Safety of Eliglustat Treatment in Gaucher Disease: Real-life Unicentric Experience.

PURPOSE: The therapy and management of Gaucher disease (GD) have radically changed with the use of substrate reduction therapy, of which eliglustat is the most widely known drug, allowing it to overcome the limits of enzyme replacement therapy (ERT). The rarity of GD and the limited use of eliglustat outside clinical trials require further study of its strengths and weaknesses. METHODS: In this study, we evaluated the effectiveness and safety of eliglustat in a cohort of 12 patients with GD followed up in our center, reporting a reduction in both chitotriosidase (394.3 vs 181.1 nmol/h/mL, P = 0.027) and glucosylsphingosine values (45.1 vs 18.9 ng/mL, P <0.001) after at least 12 months of therapy compared with baseline, regardless of patient demographic characteristics and GD characteristics. FINDINGS: There were no drug-related serious adverse effects and no drug-related cardiac events. Most adverse events were mild and transient, mainly dyspepsia and abdominal pain. Of interest, we reported an absence of statistical difference in terms of response regarding glucosylsphingosine reduction in relation to naive or prior exposure to ERT (P = 0.296), which was confirmed also when patients were placed in naive and treated groups for <5 vs >5 years (P = 0.667). IMPLICATIONS: The use of eliglustat immediately after diagnosis may guarantee the best treatment for patients with milder phenotypes or with aggressive disease after an initial stabilization with ERT compared with ERT, which cannot adequately remove the disease burden despite the apparent response, thus potentially reducing future complications caused by substrate deposits.

Therapeutic Management of Patients with FLT3 + Acute Myeloid Leukemia: Case Reports and Focus on Gilteritinib Monotherapy.

Acute myeloid leukemia is a malignant disorder of the bone marrow, characterized by differentiation, clonal expansion, and uncontrolled proliferation of malignant myeloid progenitor cells and by several molecular and genetic abnormalities. A mutation of FMS-like tyrosine kinase 3 gene can be observed in about one-third of cases of acute myeloid leukemia. Two FLT3 inhibitors are actually approved for FLT3 mutated acute myeloid leukemia: midostaurin, a multikinase first generation inhibitor with lower affinity for FLT3 binding, and gilteritinib fumarate, a potent second-generation inhibitor of both FLT3-ITD and TKD. Gilteritinib is a new effective and well-tolerated drug for patients with relapsing or refractory FLT3-positive acute myeloid leukemia. Thanks to its efficacy, low toxicity, its good manageability (oral formulation), this drug is suitable for all the patients, including elderly frail patient with concomitant therapies or pre-existing or underlying diseases, and can be used also in the outpatient setting, reducing risks and costs related to the hospitalization. We report and discuss seven cases of different patients with FLT3 positive acute myeloid leukemia successfully managed with gilteritinib in the real clinical practice.

ELN2017 risk stratification improves outcome prediction when applied to the prospective GIMEMA AML1310 protocol.

The 2017 version of the European LeukemiaNet (ELN) recommendations, by integrating cytogenetics and mutational status of specific genes, divides patients with acute myeloid leukemia into 3 prognostically distinct risk categories: favorable (ELN2017-FR), intermediate (ELN2017-IR), and adverse (ELN2017-AR). We performed a post hoc analysis of the GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) AML1310 trial to investigate the applicability of the ELN2017 risk stratification to our study population. In this trial, after induction and consolidation, patients in complete remission were to receive an autologous stem cell transplant (auto-SCT) if categorized as favorable risk or an allogeneic stem cell transplant (allo-SCT) if adverse risk. Intermediate-risk patients were to receive auto-SCT or allo-SCT based on the postconsolidation levels of measurable residual disease as measured by using flow cytometry. Risk categorization was originally conducted according to the 2009 National Comprehensive Cancer Network recommendations. Among 500 patients, 445 (89%) were reclassified according to the ELN2017 criteria: ELN2017-FR, 186 (41.8%) of 455; ELN2017-IR, 179 (40.2%) of 445; and ELN2017-AR, 80 (18%) of 455. In 55 patients (11%), ELN2017 was not applicable. Two-year overall survival (OS) was 68.8%, 51.3%, 45.8%, and 42.8% for the ELN2017-FR, ELN2017-IR, ELN2017-not classifiable, and ELN2017-AR groups, respectively (P < .001). When comparing the 2 different transplant strategies in each ELN2017 risk category, a significant benefit of auto-SCT over allo-SCT was observed among ELN2017-FR patients (2-year OS of 83.3% vs 66.7%; P = .0421). The 2 transplant procedures performed almost equally in the ELN2017-IR group (2-year OS of 73.9% vs 70.8%; P = .5552). This post hoc analysis of the GIMEMA AML1310 trial confirms that the ELN2017 classification is able to accurately discriminate patients with different outcomes and who may benefit from different transplant strategies. This trial was registered as EudraCT number 2010-023809-36 and at www.clinicaltrials.gov as #NCT01452646.

A rare case of acquired factor V inhibitor, during treatment with dabigatran for chronic atrial fibrillation, successfully treated with bypassing agents.

Acquired factor V inhibitor represents a rare condition, described only in case reports. The use of activated bypassing agents in bleeding control could be of aid and improve the survival in symptomatic patients with acquired factor V inhibitor.

Acquired hemophilia in a 7-year-old girl successfully treated with recombinant FVIIA and steroids: A case report.

Acquired hemophilia should be evaluated in pediatric patients with bleeding and isolated prolonged aPTT. Immunosuppressive treatment should be initiated even in minor bleedings. Bypassing agents like rFVIIa can be used in children with success.

A Real-Life Survey of Venous Thromboembolic Events Occurring in Myeloma Patients Treated in Third Line with Second-Generation Novel Agents.

Compared to the general population, patients with multiple myeloma (MM) have a nine-fold increased risk of developing venous thromboembolism (VTE). Little is known about VTE prophylaxis in relapsed/refractory (RR) MM patients treated with next generation anti-myeloma drugs, such as pomalidomide (Poma) and carfilzomib (K), and monoclonal antibodies daratumumab (Dara) and elotuzumab (Elo), alone or in combination with dexamethasone at high- (D, 40 mg/week) or low-dose (d, 20 mg/week). Here, we describe the incidence of VTE in a retrospective cohort of 112 consecutive relapsed and refractory myeloma (RRMM) patients who received a third line of treatment from April 2013 to February 2020. Anti-MM regimens included combinations of pomalidomide and dexamethasone (PomaD, N = 61), carfilzomib, lenalidomide and dexamethasone (KRd, N = 31), and elotuzumab, lenalidomide and dexamethasone (EloRd, N = 10), while the remaining 10 patients received daratumumab as a single agent. According to National Comprehnsive Cancer Network (NCCN), International Myeloma Working Group (IMWG) and 2015 European Myeloma Network (EMN) guidelines, 42 patients (38%) were classified as high-risk patients. According to the IMPEDE VTE score, 32 patients (28%) were classified as low-risk, with a score ≤ 3 (most of them in the PomaD and Dara group), 70 (63%) were classified as intermediate-risk, with a score of 4-7 (most of them in PomaD and KRd group), and 10 (9%) were classified as high-risk, with a score ≥8 (most of them in the PomaD group). All patients received a prophylaxis, consisting generally of low-doses of acetylsalicylic acid. VTE was recorded in 9% of our patients, all of them with an intermediate or high-risk IMPEDE score, treated with low doses aspirin (ASA). No VTE occurred in patients treated with daratumumab. Thus, our real-life experience documents that (1) in RRMM patients treated with continuative regimens of third line, the incidence of VTE is similar to the setting of newly-diagnosed patients; (2) many patients in real-life received prophylaxis with ASA, irrespective of the risk classification; (3) the IMPEDE VTE score seems to be more appropriate to define the risk categories. Randomized clinical trials are required to better define the VTE prophylaxis strategy in the RRMM setting.

Status of Recombinant Factor VIII Concentrate Treatment for Hemophilia a in Italy: Characteristics and Clinical Benefits.

The current interest in recombinant factor VIII (rFVIII) products stems from the fact that they offer a technological solution to prolonging the half-life of and reducing the risk of formation of alloantibodies (inhibitors) against FVIII in treated patients with hemophilia A (HA). The Italian health care system has authorized the use of a wide range of rFVIII concentrates of the first, second, and third generation, as well as new innovative rFVIII preparates with an extended half-life (EHL) (Kogenate FS®-Bayer, belonging to the second generation and replaced since 2017 by a product consisting of the same modified molecule; because it is only available until the end of the current year, it will not be considered in this review). Some of these products have unique pharmacodynamic and pharmacokinetic (PK) profiles, including an EHL. The first-generation full-length rFVIII (FL-rFVIII), octocog alfa (Recombinate® Baxter/BIOVIIIx), although the oldest rFVIII product, has several desirable features. Third-generation products include two modified octocog alfa molecules (Advate®, Shire; Kovaltry®, Bayer) as well as the B domain-deleted rFVIII (BDD-rFVIII) moroctocog alfa (ReFacto®-Pfizer). The B domain-truncated (BDT-rFVIII) turoctocog alfa (NovoEight®, Novo Nordisk), the BDD-rFVIII simoctocog alfa (Nuwiq®, Kedrion), the single-chain BDT-rVIII lonoctocog alfa (Afstyla®, CSL Behring), and the BDD-rFVIIIFc efmoroctocog alfa (Elocta®, Sobi-Biogen) are new, innovative products. Simoctocog alfa, because its peculiarities, is considered a fourth-generation rFVIII concentrate. Turoctocog alfa, simoctocog alfa, and lonoctocog alfa have a high affinity for von Willebrand factor (vWF) that reduces renal clearance and prolongs the half-life of rFVIII. Efmoroctocog alfa, a first-in-class rFVIII-Fc fusion protein (rFVIIIFc), has a half-life 1.5-1.8 times longer than that of conventional plasma-derived FVIII (pd-rFVIII) and other rFVIII products. Clinical studies have evaluated the efficacy, safety, and inhibitor development of all these innovative concentrates in both previously treated (PTPs) and untreated patients (PUPs). This review considers the rFVIII products that are indicated for the treatment of patients with severe HA, focusing on those that are commercially available in Italy. Their PK characteristics, immunogenicity, and clinical benefits are discussed and compared.

A rare case of multiple myeloma with intracranial extramedullary relapse: One or more myeloma clones?

In a minority of relapsed myeloma, patient's disease may spread into extramedullary sites, associated with high degrees of heterogeneity. The breadth of myeloma therapeutic armamentarium allows clinicians to manage its heterogeneous presentation, including intracranial relapses, with fair success resulting in a significant prolongation of survival.