Incidence, mortality, and survival of hematological malignancies in Northern Italian patients: an update to 2020

BackgroundHematological malignancies (HMs) represent a heterogeneous group of diseases with diverse etiology, pathogenesis, and prognosis. HMs' accurate registration by Cancer Registries (CRs) is hampered by the progressive de-hospitalization of patients and the transition to molecular rather than microscopic diagnosis. Material and methodsA dedicated software capable of automatically identifying suspected HMs cases by combining several databases was adopted by Reggio Emilia Province CR (RE-CR). Besides pathological reports, hospital discharge archives, and mortality records, RE-CR retrieved information from general and biomolecular laboratories. Incidence, mortality, and 5-year relative survival (RS) reported according to age, sex, and 4 HMs' main categories, were noted. ResultsOverall, 7,578 HM cases were diagnosed from 1996 to 2020 by RE-CR. HMs were more common in males and older patients, except for Hodgkin Lymphoma and Follicular Lymphoma (FL). Incidence showed a significant increase for FL (annual percent change (APC)=3.0), Myeloproliferative Neoplasms (MPN) in the first period (APC=6.0) followed by a significant decrease (APC=-7.4), and Myelodysplastic Syndromes (APC=16.4) only in the first period. Over the years, a significant increase was observed in 5-year RS for Hodgkin -, Marginal Zone -, Follicular - and Diffuse Large B-cell-Lymphomas, MPN, and Acute Myeloid Leukemia. The availability of dedicated software made it possible to recover 80% of cases automatically: the remaining 20% required direct consultation of medical records. ConclusionsThe study emphasizes that HM registration needs to collect information from multiple sources. The digitalization of CRs is necessary to increase their efficiency

Fatigue in newly diagnosed acute myeloid leukaemia: General population comparison and predictive factors

Objectives: This study compared the burden of fatigue between treatment-naïve patients with newly diagnosed acute myeloid leukaemia (AML) and the general population and investigated patient factors associated with fatigue severity. Methods: Pretreatment patient-reported fatigue was assessed with the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire in a sample of 463 newly diagnosed patients with AML who were enrolled in a clinical trial. Multivariable linear regression models were used to estimate the adjusted mean differences in fatigue between patients with AML and adults from the general population (n=847) by AML disease risk categories. A clinically meaningful difference in fatigue was defined as ≥3 points. Univariable and multivariable linear regression models were used to identify sociodemographic, clinical and molecular correlates of worse fatigue in patients with AML. Results: Patients with AML reported adjusted mean fatigue scores that were 7.5 points worse than the general population (95% CI -8.6 to -6.4, p<0.001). Across AML disease risk categories, adjusted mean differences in fatigue compared with the general population ranged from 6.7 points worse (patients with favourable risk: 95% CI -8.6 to -4.8, p<0.001) to 8.9 points worse (patients with poor risk, 95% CI -10.5 to -7.2, p<0.001). Overall, 91% of patients with AML reported fatigue that was equal to or worse than the general population's median fatigue score. Higher pretreatment fatigue was independently associated with female sex, WHO performance status ≥1 and lower platelet levels. Conclusions: Patients with newly diagnosed AML reported worse fatigue than the general population, and mean differences exceeded twice the threshold for clinical significance. Our findings may help to identify patients with AML most likely to benefit from supportive care interventions to reduce fatigue

Fatigue in newly diagnosed acute myeloid leukaemia: General population comparison and predictive factors

Objectives: This study compared the burden of fatigue between treatment-naïve patients with newly diagnosed acute myeloid leukaemia (AML) and the general population and investigated patient factors associated with fatigue severity. Methods: Pretreatment patient-reported fatigue was assessed with the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire in a sample of 463 newly diagnosed patients with AML who were enrolled in a clinical trial. Multivariable linear regression models were used to estimate the adjusted mean differences in fatigue between patients with AML and adults from the general population (n=847) by AML disease risk categories. A clinically meaningful difference in fatigue was defined as ≥3 points. Univariable and multivariable linear regression models were used to identify sociodemographic, clinical and molecular correlates of worse fatigue in patients with AML. Results: Patients with AML reported adjusted mean fatigue scores that were 7.5 points worse than the general population (95% CI -8.6 to -6.4, p<0.001). Across AML disease risk categories, adjusted mean differences in fatigue compared with the general population ranged from 6.7 points worse (patients with favourable risk: 95% CI -8.6 to -4.8, p<0.001) to 8.9 points worse (patients with poor risk, 95% CI -10.5 to -7.2, p<0.001). Overall, 91% of patients with AML reported fatigue that was equal to or worse than the general population's median fatigue score. Higher pretreatment fatigue was independently associated with female sex, WHO performance status ≥1 and lower platelet levels. Conclusions: Patients with newly diagnosed AML reported worse fatigue than the general population, and mean differences exceeded twice the threshold for clinical significance. Our findings may help to identify patients with AML most likely to benefit from supportive care interventions to reduce fatigue

Predictors of Response to Hydroxyurea and Switch to Ruxolitinib in HU-Resistant Polycythaemia VERA Patients: A Real-World PV-NET Study

: In polycythemia vera (PV), the prognostic relevance of an ELN-defined complete response (CR) to hydroxyurea (HU), the predictors of response, and patients' triggers for switching to ruxolitinib are uncertain. In a real-world analysis, we evaluated the predictors of response, their impact on the clinical outcomes of CR to HU, and the correlations between partial or no response (PR/NR) and a patient switching to ruxolitinib. Among 563 PV patients receiving HU for ≥12 months, 166 (29.5%) achieved CR, 264 achieved PR, and 133 achieved NR. In a multivariate analysis, the absence of splenomegaly (p = 0.03), pruritus (p = 0.002), and a median HU dose of ≥1 g/day (p < 0.001) remained associated with CR. Adverse events were more frequent with a median HU dose of ≥1 g/day. Overall, 283 PR/NR patients (71.3%) continued HU, and 114 switched to ruxolitinib. In the 449 patients receiving only HU, rates of thrombosis, hemorrhages, progression, and overall survival were comparable among the CR, PR, and NR groups. Many PV patients received underdosed HU, leading to lower CR and toxicity rates. In addition, many patients continued HU despite a PR/NR; however, splenomegaly and other symptoms were the main drivers of an early switch. Better HU management, standardization of the criteria for and timing of responses to HU, and adequate intervention in poor responders should be advised

Ruxolitinib discontinuation syndrome: incidence, risk factors, and management in 251 patients with myelofibrosis

none36Ruxolitinib discontinuation syndrome: incidence, risk factors, and management in 251 patients with myelofibrosisopenPalandri F.; Palumbo G.A.; Elli E.M.; Polverelli N.; Benevolo G.; Martino B.; Abruzzese E.; Tiribelli M.; Tieghi A.; Latagliata R.; Cavazzini F.; Bergamaschi M.; Binotto G.; Crugnola M.; Isidori A.; Caocci G.; Heidel F.; Pugliese N.; Bosi C.; Bartoletti D.; Auteri G.; Cattaneo D.; Scaffidi L.; Trawinska M.M.; Stella R.; Ciantia F.; Pane F.; Cuneo A.; Krampera M.; Semenzato G.; Lemoli R.M.; Iurlo A.; Vianelli N.; Cavo M.; Breccia M.; Bonifacio M.Palandri, F.; Palumbo, G. A.; Elli, E. M.; Polverelli, N.; Benevolo, G.; Martino, B.; Abruzzese, E.; Tiribelli, M.; Tieghi, A.; Latagliata, R.; Cavazzini, F.; Bergamaschi, M.; Binotto, G.; Crugnola, M.; Isidori, A.; Caocci, G.; Heidel, F.; Pugliese, N.; Bosi, C.; Bartoletti, D.; Auteri, G.; Cattaneo, D.; Scaffidi, L.; Trawinska, M. M.; Stella, R.; Ciantia, F.; Pane, F.; Cuneo, A.; Krampera, M.; Semenzato, G.; Lemoli, R. M.; Iurlo, A.; Vianelli, N.; Cavo, M.; Breccia, M.; Bonifacio, M

Life after ruxolitinib: Reasons for discontinuation, impact of disease phase, and outcomes in 218 patients with myelofibrosis

Background: After discontinuing ruxolitinib, the outcome of patients with myelofibrosis reportedly has been poor. The authors investigated whether disease characteristics before the receipt of ruxolitinib may predict drug discontinuation in patients with myelofibrosis and whether reasons for drug discontinuation, disease phase at discontinuation, and salvage therapies may influence the outcome. Methods: A centralized electronic clinical database was created in 20 European hematology centers, including clinical and laboratory data for 524 patients who received ruxolitinib for myelofibrosis. Results: At 3\ua0years, 40.8% of patients had stopped ruxolitinib. Baseline predictors of drug discontinuation were: intermediate-2\u2013risk/high-risk category (Dynamic International Prognostic Score System), a platelet count <100 7109 per liter, transfusion dependency, and unfavorable karyotype. At last contact, 268 patients (51.1%) had discontinued therapy, and the median drug exposure was 17.5\ua0months. Fifty patients (18.7%) died while taking ruxolitinib. The reasons for discontinuation in the remaining 218 patients were the lack (22.9%) or loss (11.9%) of a spleen response, ruxolitinib-related adverse events (27.5%), progression to blast phase (23.4%), ruxolitinib-unrelated adverse events (9.2%), and allogeneic transplantation during response (5.1%). The median survival after ruxolitinib was 13.2\ua0months and was significantly better in the 167 patients who discontinued ruxolitinib in chronic phase (27.5 vs 3.9\ua0months for those who discontinued in blast phase; P\ua0<.001). No survival differences were observed among patients who discontinued ruxolitinib in chronic phase because of lack of response, loss of response, or ruxolitinib-related adverse events. The use of investigational agents and/or ruxolitinib rechallenge were associated with improved outcome. Conclusions: The survival of patients with myelofibrosis after discontinuation of ruxolitinib is poor, particularly for those who discontinue in blast phase. Salvage therapies can improve outcome, emphasizing the need for novel therapies

Ruxolitinib in cytopenic myelofibrosis: Response, toxicity, drug discontinuation, and outcome

BackgroundPatients with cytopenic myelofibrosis (MF) have more limited therapeutic options and poorer prognoses compared with patients with the myeloproliferative phenotype. Aims and MethodsPrognostic correlates of cytopenic phenotype were explored in 886 ruxolitinib-treated patients with primary/secondary MF (PMF/SMF) included in the RUX-MF retrospective study. Cytopenia was defined as: leukocyte count &lt;4 x 10(9)/L and/or hemoglobin &lt;11/&lt;10 g/dL (males/females) and/or platelets Overall, 407 (45.9%) patients had a cytopenic MF, including 249 (52.4%) with PMF. In multivariable analysis, high molecular risk mutations (p = .04), intermediate 2/high Dynamic International Prognostic Score System (p &lt; .001) and intermediate 2/high Myelofibrosis Secondary to Polycythemia Vera and Essential Thrombocythemia Prognostic Model (p &lt; .001) remained associated with cytopenic MF in the overall cohort, PMF, and SMF, respectively. Patients with cytopenia received lower average ruxolitinib at the starting (25.2 mg/day vs. 30.2 mg/day, p &lt; .001) and overall doses (23.6 mg/day vs. 26.8 mg/day, p &lt; .001) and achieved lower rates of spleen (26.5% vs. 34.1%, p = .04) and symptom (59.8% vs. 68.8%, p = .008) responses at 6 months compared with patients with the proliferative phenotype. Patients with cytopenia also had higher rates of thrombocytopenia at 3 months (31.1% vs. 18.8%, p &lt; .001) but lower rates of anemia (65.6% vs. 57.7%, p = .02 at 3 months and 56.6% vs. 23.9% at 6 months, p &lt; .001). After competing risk analysis, the cumulative incidence of ruxolitinib discontinuation at 5 years was 57% and 38% in patients with cytopenia and the proliferative phenotype (p &lt; .001), whereas cumulative incidence of leukemic transformation was similar (p = .06). In Cox regression analysis adjusted for Dynamic International Prognostic Score System score, survival was significantly shorter in patients with cytopenia (p &lt; .001). ConclusionsCytopenic MF has a lower probability of therapeutic success with ruxolitinib as monotherapy and worse outcome. These patients should be considered for alternative therapeutic strategies