Standard dose and prolonged administration of azacitidine are associated with improved efficacy in a real-world group of patients with myelodysplastic syndrome or low blast count acute myeloid leukemia.

OBJECTIVE: Azacitidine is the standard of care for higher-risk myelodysplastic syndromes (MDS). We evaluated factors affecting the outcome of azacitidine treatment in 196 'real-world' patients, retrospectively collected by two Italian cooperative groups. METHODS: The study included 184 MDS and 12 low blast count acute myeloid leukemia (AML). Azacitidine was administered at the standard dose of 75 mg/m(2)/d for 7 d (SD) in 163 patients and 100 mg/d for 5-7 d in 33 patients. RESULTS: After a median of 4.5 azacitidine cycles (range 7-15 cycles), 182 patients were evaluable for response. Nineteen percent achieved complete remission (CR), 17% partial remission (PR), and 21% hematological improvement (HI). The disease was stable or progressive in 29% and 14% of patients, respectively. The probability of response was significantly higher in patients who received the 75 mg/m(2)/7 d compared with 100 mg through 5-7 d dose (CR/PR/HI: 63 vs. 29%, P = 0.0005). Median overall survival was 17.1 months. Low MDS-CI and achievement of CR/PR/HI were significant predictors of survival in the multivariable analysis. CONCLUSIONS: Our data show that maximal azacitidine efficacy is associated with the standard dose and with prolonged treatment, beyond 4-6 cycles, with the goal of also improving the 'quality' of response. Lower MDS-CI and IPSS-R scores, hematologic response and disease stability, are associated with longer survival. The risk of febrile events is highest during the first treatment cycles and is associated with active disease.

Evaluation of serological response to anti-SARS-CoV-2 mRNA vaccination in hematological patients.

Introduction: In immunocompromised patients, SARS-CoV-2 mRNA vaccine has been used in Italy from the beginning of the vaccination campaign, but several studies have shown that the serological response of onco-hematological patients was reduced compared to healthy subjects, due to the state of immunosuppression because of both underlying disease and administered therapy. Methods: We evaluated the association of anti-SARS-CoV-2 spike IgG titers in 215 hematological patients with clinical and demographic variables to verify if it was possible to identify predictive parameters of serological response, as well as using a control group, consisting of healthy health workers of San Carlo Hospital in Potenza. Anti-SARS-CoV2 IgG titers were evaluated after 30-45 days post second dose vaccine using chemiluminescent microparticle immunoassay technology. Results: Patients with hematological malignancies, compared with the control arm, had both a mean concentration of anti-SARS-CoV-2 IgG significantly lower and a seroconversion rate numerically lower. All chronic lymphatic leukemia patients showed levels of antibody titer below the mean concentration, also in only clinical surveillance patients. Comparing serological response in hematological malignancies, only acute leukemia patients who were off therapy had the highest seroconversion rate among the patients' cohorts and a mean antibody concentration greater than the control arm. Patients treated with steroids and rituximab showed a lower level of anti-SARS-CoV-2 spike IgG. Differences in anti-spike IgG levels among chronic myeloid leukemia patients stratified according to tyrosine kinase inhibitor therapy and molecular response were observed, and they could have interesting implications on the evaluation of the effects of these drugs on the immune system, but having not reached statistical significance at the moment. The cohort of patients who received a stem cell transplant was very heterogeneous because it included different hematological malignancies and different types of transplant; however, a mean concentration of anti-SARS-CoV2 IgG greater than the control arm was reported. Indeed, among patients who performed a transplant for over 6 months only one had a spike IgG concentration below the cutoff. Conclusions: Our data confirm reduced serological response in hematological patients after anti-SARS-CoV-2 vaccination. However, we found a great diversity of SARS-CoV-2 antibody response according to types of pathologies and therapies.

Efficacy and safety of bortezomib in patients with plasma cell leukemia.

BACKGROUND: The prognosis of patients with plasma cell leukemia (PCL), an aggressive variant of multiple myeloma (MM), is usually poor. Bortezomib is the first proteasome inhibitor approved for the treatment of advanced MM. Currently available information regarding the role of bortezomib in PCL is scanty and derives from anecdotal, single-case reports. METHODS: The authors conducted a retrospective survey of unselected Italian patients with primary or secondary PCL who were treated with bortezomib outside of clinical trials. Twelve evaluable patients were recorded who had received bortezomib for 1 to 6 cycles as either a single agent or variously combined with other drugs. Three patients were treated with bortezomib as frontline therapy, and 9 patients received bortezomib after 1 to 4 lines of chemotherapy, including autologous stem cell transplantation and thalidomide. RESULTS: According to the International uniform response criteria of the International Myeloma Working Group, 5 partial responses (defined as a reduction in M-protein of >50%), 4 very good partial responses (defined as a reduction of >90% in M-protein), and 2 complete responses (defined as negative immunofixation) were achieved, for a response rate of 92%. Responses did not appear to be influenced by previous treatments or by other clinical or biologic parameters, including chromosome 13 deletion or the combination of bortezomib with other drugs. The median progression-free and overall survivals after bortezomib were 8 months and 12 months, respectively. At the time of last follow-up, 8 patients were alive 6 to 21 months after treatment with bortezomib, 4 of whom were in very good partial or complete responses. Grade 3/4 hematologic or neurologic toxicities (graded according to the Common Terminology Criteria for Adverse Events [CTCAE; version 3]) were reported to occur in 9 patients and 1 patient, respectively, whereas 6 patients experienced possible or documented infections. CONCLUSIONS: Bortezomib appears to be an effective drug for PCL that could significantly improve the usually adverse clinical outcome of these patients.