Based on the results obtained in clinical trials, the use of the combination of lenalidomide and dexamethasone (Len/Dex) has become a potential therapeutic choice for newly diagnosed multiple myeloma (NDMM) ineligible for autologous stem cell transplantation. This study evaluated 89 frail NDMM patients treated with first-line oral association. At the last follow-up, 34 out of 89 patients (38.2%) were alive, and 22 were still in treatment with Len/Dex. Among 73 evaluable patients who received at least two cycles, the overall response rate was 71% (N = 52). The disease control rate, defined as any level of clinical response to therapy, occurred in 71 patients (97%). We reported one or more adverse events of grade 3 or 4 (G3/4) in 65.2% (N = 58) of patients, with a prevalence of hematological toxicity (24 patients), leading to an overall discontinuation of treatment in two cases. In univariate analysis, high ISS, high serum β2-microglobulin, and creatinine clearance <30 mL/min negatively impact OS, while the depth of response positively impacts OS. Moreover, G3-4 anemia, ISS, frailty score, and ECOG negatively impacts PFS. In conclusion, elderly and more frail patients benefit from the Len/Dex combination also in the era of monoclonal antibodies, ensuring an increased PFS and OS in patients where the therapeutic choice is often limited and usually not very effective.

Background: In the era of novel drugs a growing number of multiple myeloma (MM) patients are treated until disease progression. Serum free light chain (sFLC) assay is recommended for disease monitoring in oligo-secretory and micromolecular MM. Methods: In this real-life survey, a total of 130 relapsed/refractory MM patients treated at our center with at least three lines were investigated as a retrospective cohort. Results: The median age at diagnosis was 64 years and more than half of patients were male. A total of 24 patients (18%) had oligo-secretory/micromolecular disease at diagnosis. More than 20% of 106 normo-secretory patients had oligo-secretory/micromolecular escape. In order to evaluate potential role of sFLC assay before (“pre”) and after (“post”) every treatment line, involved serum free light chain values (iFLC) less than 138 mg/mL and serum free light chain ratios (FLCr) <25 were identified by using ROC curve analysis. The analysis of the entire cohort throughout four treatment lines demonstrated a statistically significant negative impact on progression-free survival (PFS) for both involved pre-sFLC and its ratio (respectively p = 0.0086 and p = 0.0065). Furthermore, both post-iFLC and post-FLCr greater than the pre-established values had a negative impact on PFS of the study cohort; respectively, p = 0.014 and p = 0.0079. Odds ratio analysis evidenced that patients with both involved post-sFLC greater than 138 mg/mL and post-FLCr above 25 at disease relapse had a higher probability of having clinical relapse (respectively p = 0.026 and p = 0.006). Conclusions: Alterations of sFLC values, namely iFLC and FLCr, both prior to treatment initiation and in the course of therapy at every treatment line, could be of aid in relapse evaluation and treatment outcome. We therefore suggest close periodical monitoring of sFLC assay, independently from secretory status.

Background: Clinical course of COVID-19 depends on several patient-specific risk factors, including immune function, that is largely compromised in cancer patients. Methods: We prospectively evaluated 120 adult consecutive patients (including 34 cases of COVID-19 breakthrough after two full doses of BNT162b2 vaccine) with underlying hematological malignancies and a SARS-CoV-2 infection, in terms of patient’s clinical outcome. Results: Among fully vaccinated patients the achievement of viral clearance by day 14 was more frequent than in unvaccinated patients. Increased 30-day mortality was associated with presence of active/progressing disease and absolute monocyte count lower than 400 cells/uL. Results of multivariable analysis in unvaccinated patients showed that the pre-infection absolute count of monocytes less or equal to 400 cells/mmc, active or progressive disease of the underlying hematological malignancy, the COVID-19 severity identified by hospitalization requirement and lack of viral clearance at 14 days were independent predictors of 1-year overall survival. Conclusions: Taken together, our results indicate that absolute monocyte count determined one month before any documented SARS-CoV-2 infection could identify patients affected by hematological neoplasms with increased risk of inferior overall survival.

Background: Immune system impairment is frequently reported in patients affected by hemoglobinopathies due to various mechanisms, including iron accumulation, antigenic stimulation due to numerous transfusions, chronic hemolysis, and a general hyperinflammatory state. For these reasons, the antigenic immune response after a vaccine risks being ineffective. Methods: We evaluated the anti-spike IgG production after two doses of vaccine for SARS-CoV-2 in patients affected by hemoglobinopathies. Results: All 114 enrolled patients (100%) developed adequate antibody production, with a median value of serum IgG of 2184.4 BAU/mL (IQR 1127.4–3502.9). The amount of antibody was unrelated to any other clinical characteristics evaluated, including transfusion dependence or non-transfusion dependence, age, gender, disease type, ferritin, blood count, spleen status, and therapy with hydroxyurea or iron chelators (in all the cases p > 0.05). Moreover, 47 (41.2%) patients developed breakthrough SARS-CoV-2 infection during the first 2 years of follow-up after vaccination, all with a mildly symptomatic course, without requiring hospitalization or experiencing a significative drop in hemoglobin values, allowing for a slight delay in their transfusion regimen. Conclusion: Vaccination against COVID-19 is safe and effective for patients affected by hemoglobinopathies, ensuring adequate protection from severe infection.

Objectives: Sickle Cell Disease (SCD) has a significant impact on the musculoskeletal system. The use of the Oxford Hip (OHS) and Shoulder score (OSS) as patient-reported outcome measures (PROMs) revealed a high rate of long-term impairment in joints with a pre-existing diagnosis of avascular necrosis (AVN). With this study, we aimed at detecting dysfunction in joints apparently not affected by AVN. Methods: This is a subgroup analysis of a previous core study assessing the OHS and OSS in 47 SCD patients with a pre-existing diagnosis of AVN. For this study, only patients with a pre-existing diagnosis of isolated AVN (only hip or only shoulder) were selected, and the OHS or OSS was measured in previously unaffected joints. Results: Among 37 patients with isolated AVN, 19 (51%) patients presented abnormal scores in the apparently unaffected joint; 16 (50%) patients with pre-existing isolated hip AVN had an abnormal OSS; and 9 (56%) had moderate to severe shoulder impairment. All patients with pre-existing isolated shoulder AVN had an abnormal OHS, with severe hip impairment in two out of three. As per clinical practice, patients with an abnormal score were prescribed joint magnetic resonance imaging (MRI) and/or X-rays. Only 10 out 19 (53%) performed imaging studies and all showed signs of AVN. Conclusions: Abnormal OHS and OSS values indicated a high rate of joint dysfunction in sites apparently not affected by AVN. The routine use of these PROMs should be applied to all SCD adults and subjects with a pathological score should have priority access to diagnostic radiological tests.