Background: SARS-COV-2 anti-Spike IgG response following mRNA vaccination (BNT162b2) is suboptimal and highly variable in MM patients. Patients and Methods: We report here a single-institution retrospective analysis of 127 consecutive patients with symptomatic MM (71 males, 56 females), [median age 69.5 years (range 45-85)], 63 patients with untreated MM and 64 patients with MM refractory to one or more previous treatment lines. Myeloma therapies included PI+IMiD combos, IMiD-based regimens, PI-based regimens, anti-CD38 mAb-based therapies, antibody-drug conjugates (Belantamab Mafodotin monotherapy), dexamethasone and high dose melphalan. Anti-spike IgG antibody were detected also in 50 healthy volunteers. Patients with symptomatic MM and healthy controls received two dose of COVID-19 mRNA vaccine (Pfizer BioNTech) on days 1 and 21 between 29 April and 15 May 2021. Patients with prior history of SARS-CoV-2 were excluded from analysis. Quantitative determination of anti-spike S1/S2 IgG antibody was performed at 4 weeks from vaccination completion (LIAISON® SARS-COV-2 S1/S2 IgG, LIAISON®). It was previously established a threshold >15 AU/ml of anti-Spike IgG which was related to neutralizing activity of anti-SARS-COV-2 antibodies. Results: Sixty-five out of 127 patients were evaluable for response. Anti-spike IgG antibody were detected in 50/65 (76.9%) MM patients, defined as responders [177 AU/mL (range 26.4 – 1430)]. 23.1% of MM patients, defined as non-responders, failed to respond at two doses of COVID-19 mRNA vaccine [3.8 AU/mL (range 0.65 – 9.33)]. Seroprotection rate at cutoff of 15 AU/mL was 100% in controls [249 AU/mL (range 104 - 2430)]. No statistically significant differences were found between the two subgroups of patients for myeloma disease phase (relapse/refractory MM vs. untreated symptomatic MM), LDH, residual gammaglobulin levels, WBC, ANC, lymphocytic response, age and sex (Tab. 2). Conversely, plasmacytosis, B2M and haemoglobin concentration were associated with a different response to vaccine. Patients with extreme plasmacytosis (60.0 ± 20.3 vs. 28.2 ± 18.8 mean ± SD; p <0.001) (Tab. 2) had a mean titer less than 15 AU/ml of anti-Spike IgG compared with patients with a low plasmacytosis, who, conversely, showed significantly higher mean titers of anti-Spike IgG. B2M was significantly higher in non-responders compared to responders (4.6 ± 4.1 vs. 3.2 ± 3.6 mean ± SD; p = 0.006) (Tab. 2). Haemoglobin value was significantly lower in non-responders compared to responders (10.8 ± 1.8 vs. 12.1 ± 1.8 mean ± SD; p = 0.008) (Tab. 2). Multivariate analysis confirmed the bone marrow infiltration pattern and haemoglobin value as statistically significant variables. In addition, in the present cohort, the myeloma treatment, including high-dose melphalan and autologous stem cell transplantation, have not been associated with SARS-CoV-2 infection. Conclusions: In our experience, significant fraction of MM patients (23.1%) does not developed any detectable anti-Spike IgG after two dose of COVID-19 mRNA vaccine. Lack of IgG response associated with three statistically significant variables: extreme plasmacytosis, B2M, and haemoglobin concentration. In the subgroup of patients with good response to vaccine, after a median follow-up of 7 months from second dose of COVID-19 mRNA vaccine, no cases of COVID-19 occurred.
Abstract: Quantitative measurements of circulating free immunoglobulin light chains (FLC) and of biomarkers such as N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponins (cTnT ...
Data on caplacizumab use for thrombotic thrombocytopenic purpura (TTP) in Italy are missing.• Twenty-six Italian patients were treated with caplacizumab for an acute immune TTP episode.• Caplacizumab was effective in treating acute TTP in the Italian real-world clinical setting.• Two major bleeds leading to drug discontinuation were observed.
Abstract Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy (TMA) characterized by the severe deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity (< 10%). Rapid ADAMTS13 testing is crucial for an early diagnosis and optimal management of acute TTP. We evaluated the performance of the HemosIL AcuStar ADAMTS13 activity assay (Instrumentation Laboratory, Bedford, Massachusetts, United States), a fully automated chemiluminescent immunoassay with an analytical time of 33 minutes. A method comparison study was performed on 176 samples from 49 healthy donors and 127 TMA patients (109 TTP, 7 atypical hemolytic uremic syndrome, 11 other TMAs), comparing this new assay with an in-house FRETS-VWF73 assay and a commercial enzyme-linked immunosorbent assay (ELISA) (TECHNOZYM ADAMTS-13 Activity, Technoclone GmbH, Vienna, Austria). Agreement between methods was assessed with focus on ADAMTS13 activity less than 10%, the medical decision level relevant for TTP diagnosis. The HemosIL AcuStar ADAMTS13 Activity showed good correlation with both the FRETS-VWF73 (r = 0.96) and ELISA (r = 0.96) methods. Slope of the Passing–Bablok regression was 1.05 for FRETS-VWF73 and 1.02 for ELISA, and absolute bias at the medical decision level was +0.1 and +0.3%, respectively. The study also revealed high agreement with FRETS-VWF73 (kappa 0.97) and ELISA (kappa 0.98) methods in classifying TTP patients with a severe deficiency of ADAMTS13 activity. Because of its short turnaround time and full automation, the HemosIL AcuStar ADAMTS13 activity assay might become the assay of choice to rapidly test ADAMTS13 activity in plasma and thus establish the diagnosis of acute TTP in emergency settings.
Background: Myelodisplastic syndromes (MDS) are an heterogeneous group of hematologic that frequently progress in acute myeloid leukemia (secondary AML, s‐AML). The hypomethylating agents azacitidine (AZA) and decitabine (DAC) are currently approved for the treatment of several specific subtypes of MDS and AML. Aims: Our aim is to suggest that DAC has a favourable efficacy and safety profile as rescue therapy after AZA failure Methods: We report a short case series of 4 patients referred to our institution with s‐AML occurring after MDS and MDS/MPN in accelerated phase treated with DAC following AZA failure used for MDS phase treatment. At the time of diagnosis, median age of patients was 73 (range 68‐78), all patients were Intermediate‐2 according to IPSS and they had RBC transfusion dependency. All patients underwent blood cell count samples, bone marrow biopsy and conventional cytogenetic assays to confirm diagnosis. Results: The 1 st patient was a 78‐years‐old woman with anemia (red blood cell transfusion dependency about 4‐5 RBC units/month) and 15% of bone marrow blasts diagnostic for MDS‐EB‐2. Cytogenetic analysis showed a normal karyotype. She started treatment with azacytidine sc at 75 mg/sm/day for 7 days in 28‐day cycles. After 11 courses the patient showed treatment failure with progression to AML (hyperleukocytosis WBC 150.000/microL, bone marrow blasts 40% and monosomy 8), thus she started treatment with decitabine iv at 20 mg/sm for 5 days in 28‐day cycles plus hydroxyurea. A bone marrow biopsy done after 4 and 8 cycles showed 10% and 8% of blasts, respectively. After 9 th cycle she died due to chronic obstructive pulmonary disease worsening. The 2 nd patient was a 72‐years‐old man with thrombocytosis and anemia (red blood cell transfusion dependency about 1‐2 RBC units/month) and 15% of bone marrow blasts diagnostic for MDS/MPN in accelerated phase. He started treatment with azacytidine sc at 75 mg/sm/day for 7 days in 28‐day cycles. After 24 courses of azacytidine he showed progression to AML (bone marrow blasts 30% and fibrosis), thus he started decitabine iv at 20 mg/sm for 5 days in 28‐day cycles. After 1st cycle the patient obtained a transfusion indipendency lasted for the following 3 cycles. After 4 th cycle he developed pancytopenia, therefore a BM assay showed 50% of blasts. Finally the patient died for infectiuos complications. The 3 rd patient was a 68‐years‐old woman with a diagnosis of MDS‐EB‐2 (bone marrow blasts 15%), normal karyotype and a red blood cell transfusion dependency of about 1‐2 RBC units/month. She started azacytidine sc at 75 mg/sm/day for 7 days in 28‐day cycles. After 32 courses the disease progressed to AML (70% of blasts), thus she started therapy with decitabine 20 mg/sm for 5 days every 28 days achieving a partial response. At the end of 4th cycle she died due to cerebral hemorrhage. The 4 th patient was a 74‐years‐old man treated with azacitidine (75 mg/sm for 7 days every 28 days) for a MDS‐EB‐2 (bone marrow blasts 10%, normal karyotype. He had a red blood cell transfusion dependency of about 1‐2 RBC units/month). After 10 cycles of azacytidine he showed therapy failure with progression to AML (bone marrow blasts 80%), so he started decitabine 20 mg/sm for 5 days every 28 days, discontinued after 2 courses due to clinical worsening Summary/Conclusion: In this short monocentric case series DAC demonstrated a favourable efficacy and safety profile as rescue therapy after AZA failure, also improving survival (median OS 7 months).
