Implications of interleukin-6 (Il-6)-blockade for severe covid-19 infection in patients with multiple myeloma

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"Hemolysis, or not hemolysis, that is the question". Use of hydroxychloroquine in a patient with COVID-19 infection and G6PD deficiency

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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

A Comparison of the Conditioning Regimens BEAM and FEAM for Autologous Hematopoietic Stem Cell Transplantation in Lymphoma: An Observational Study on 1038 Patients From Fondazione Italiana Linfomi

Abstract Background Carmustine (BCNU)-Etoposide-Citarabine-Melphalan (BEAM) chemotherapy is the standard conditioning regimen for autologous stem cell transplantation (ASCT) in lymphomas. Owing to BCNU shortages, many centers switched to Fotemustine-substituted BEAM (FEAM), lacking proof of equivalence. Methods We conducted a retrospective cohort study in 18 Italian centers to compare safety and efficacy of BEAM and FEAM regimens for ASCT in lymphomas performed from 2008 to 2015. Results We enrolled 1038 patients (BEAM n=607, FEAM n=431), of which 27% had Hodgkin's lymphoma (HL), 14% indolent Non-Hodgkin's lymphoma (iNHL) and 59% aggressive NHL (aNHL). Baseline characteristics including age, sex, stage, B-symptoms, extranodal involvement, previous treatments, response before ASCT, overall conditioning intensity, were well balanced between BEAM and FEAM; notable exceptions were: ASCT year (median: BEAM=2011 vs FEAM=2013, p Conclusions BEAM and FEAM do not appear different in terms of survival and disease control. However, due to concerns of higher toxicity, Fotemustine substitution in BEAM does not seem justified, if not for easier supply

Low low-density lipoprotein (LDL), cholesterol and triglycerides plasma levels are associated with reduced risk of arterial occlusive events in chronic myeloid leukemia patients treated with ponatinib in the real-life. A Campus CML study

36noopenopenCaocci G.; Mulas O.; Capodanno I.; Abruzzese E.; Iurlo A.; Luciano L.; Albano F.; Annunziata M.; Tiribelli M.; Bonifacio M.; Galimberti S.; Castagnetti F.; Sgherza N.; Stagno F.; Gozzini A.; Orlandi E.M.; Luzi D.; Binotto G.; Pregno P.; Fozza C.; Efficace F.; Simula M.P.; Trawinska M.M.; Cattaneo D.; De Gregorio F.; Attolico I.; Stella R.; Scaffidi L.; Barate C.; Gugliotta G.; Scalzulli E.; Elena C.; Pirillo F.; Foa R.; Breccia M.; Nasa G.L.Caocci, G.; Mulas, O.; Capodanno, I.; Abruzzese, E.; Iurlo, A.; Luciano, L.; Albano, F.; Annunziata, M.; Tiribelli, M.; Bonifacio, M.; Galimberti, S.; Castagnetti, F.; Sgherza, N.; Stagno, F.; Gozzini, A.; Orlandi, E. M.; Luzi, D.; Binotto, G.; Pregno, P.; Fozza, C.; Efficace, F.; Simula, M. P.; Trawinska, M. M.; Cattaneo, D.; De Gregorio, F.; Attolico, I.; Stella, R.; Scaffidi, L.; Barate, C.; Gugliotta, G.; Scalzulli, E.; Elena, C.; Pirillo, F.; Foa, R.; Breccia, M.; Nasa, G. L

Elotuzumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: a multicenter, retrospective, real-world experience with 200 cases outside of controlled clinical trials

In the ELOQUENT-3 trial, the combination of elotuzumab, pomalidomide , dexamethasone (EloPd) proved to have a superior clinical benefit over pomalidomide and dexamethasone with a manageable toxicity profile, leading to its approval for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. We report here a real-world experience of 200 cases of RRMM treated with EloPd in 35 Italian centers outside of clinical trials. In our dataset, the median number of prior lines of therapy was two, with 51% of cases undergoing autologous stem cell transplant and 73% having been exposed to daratumumab. After a median follow-up of 9 months, 126 patients had stopped EloPd, most of them (88.9%) because of disease progression. The overall response rate was 55.4%, a finding in line with the pivotal trial results. Regarding adverse events, the toxicity profile in our cohort was similar to that in the ELOQUENT-3 trial, with no significant differences between younger (&lt;70 years) and older patients. The median progression-free survival was 7 months, which was shorter than that observed in ELOQUENT-3, probably because of the different clinical characteristics of the two cohorts. Interestingly, International Staging System stage III disease was associated with worse progression-free survival (hazard ratio=2.55). Finally, the median overall survival of our series was shorter than that observed in the ELOQUENT-3 trial (17.5 vs. 29.8 months). In conclusion, our real-world study confirms that EloPd is a safe and possible therapeutic choice for patients with RRMM who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor

Observational study of chronic myeloid leukemia italian patients who discontinued tyrosine kinase inhibitors in clinical practice

It is judged safe to discontinue treatment with tyrosine kinase inhibitors (TKI) for chronic myeloid leukemia (CML) in experimental trials on treatment-free remission (TFR). We collected a total of 293 Italian patients with chronic phase CML who discontinued TKI in deep molecular response. Seventy-two percent of patients were on treatment with imatinib, and 28% with second generation TKI at the time of discontinuation. Median duration of treatment with the last TKI was 77 months [Interquartile Range (IQR) 54;111], median duration of deep molecular response was 46 months (IQR 31;74). Duration of treatment with TKI and duration of deep molecular response were shorter with second generation TKI than with imatinib (P&lt;0.001). Eighty-eight percent of patients discontinued as per clinical practice, and reasons for stopping treatment were: toxicity (20%), pregnancy (6%), and shared decision between treating physician and patient (62%). After a median follow up of 34 months (range, 12-161) overall estimated TFR was 62% (95%CI: 56;68). At 12 months, TFR was 68% (95%CI: 62;74) for imatinib, 73% (95%CI: 64;83) for second generation TKI. Overall median time to restart treatment was six months (IQR 4;11). No progressions occurred. Although our study has the limitation of a retrospective study, our experience within the Italian population confirms that discontinuation of imatinib and second generation TKI is feasible and safe in clinical practice

Onset of chronic myeloid leukemia with complex karyotype in a pregnant patient: case report and revision of literature

Nicola Sgherza,1 Elisabetta Abruzzese,2 Gianni Perla,1 Maria Marta Minervini,1 Vincenzo Chiello,1 Natale Sciannam&egrave;,3 Nicola Cascavilla1 1Hematology, IRCCS &ldquo;Casa Sollievo della Sofferenza&rdquo;, San Giovanni Rotondo (FG), 2Hematology, Sant&rsquo;Eugenio Hospital, Roma, 3Gynecology and Obstetrics, IRCCS &ldquo;Casa Sollievo della Sofferenza&rdquo;, San Giovanni Rotondo (FG), Italy Abstract: Approximately 10%&ndash;12% of patients in chronic-phase chronic myeloid leukemia (CP-CML) have additional chromosomal aberrations at diagnosis; moreover, CML occurs in up to 10% of pregnancy-associated leukemias, with an annual incidence of 1 per 100,000 pregnancies. In this report we describe the case of a 36-year-old female with CP-CML diagnosed in the 18th week of pregnancy and with a new complex variant translocation t(4;9;22;21)(q24;q34;q11;q22) and an additional chromosomal aberration t(1;20)(p36;p11). In consideration of her pregnancy, the patient strictly monitored her blood cell count without any specific treatment. At 32 weeks of pregnancy, the patient delivered via cesarean section a healthy baby girl. After 10 days from childbirth, dasatinib was started at a standard dosage of 100 mg/day and 3 months later complete cytogenetic response and major molecular response were obtained, with the achievement of an optimal response according to European Leukemia Net recommendations and showing efficacy of this tyrosine kinase inhibitor (TKI) in the presence of a complex karyotype. Keywords: chronic myeloid leukemia, complex karyotype, pregnancy, additional chromosomal aberration, variant translocation, tyrosine kinase inhibito