B cell-targeting strategies such as rituximab are widely used in B cell hematologic malignancies, rheumatologic and musculoskeletal diseases and a variety of autoimmune disorders. The purpose of this paper is to illustrate how exposure to anti-CD20 treatment profoundly affects B cell functions involved in anti-SARS-CoV-2 immunity and significantly impacts on the clinical and serological course of SARS-CoV-2 infection, long term immunity and vaccine responses. The data presented here suggest that the effects of B cell-depleting agents on adaptive immunity should be taken into account for the proper selection and interpretation of SARS-CoV-2 diagnostics and to guide appropriate therapeutic approaches and protective measures. Combination therapeutic strategies including immunotherapy in association with prolonged antiviral treatment may play a decisive role in the setting of B cell immune deficiencies.

Background: Daratumumab is a humanized monoclonal antibody approved for the treatment of adult patients with newly diagnosed or relapsed/refractory multiple myeloma (RRMM). Subcutaneous (SC) formulation proved to be non‐inferior in comparison with intravenous (IV) administration route. This study aimed at assessing the economic and time impact associated with the use of SC versus IV daratumumab in patients with RRMM from the perspective of the hematology center.Methods: This was a 5‐month multicenter time‐and‐motion cross‐sectional micro‐costing study conducted in three Italian hematology centers among adult patients diagnosed with RRMM with ongoing treatment with IV or SC daratumumab. Measurements were performed by an ad hoc App.Results: Nineteen (20%) IV and 76 (80%) SC administration procedures were measured. Patients spent a mean of 4.85 ± 0.91 or 1.08 ± 0.56 h in the hematology center to receive IV or SC daratumumab, respectively. Healthcare professionals (HCPs) spent a mean of 49.38 ± 16.13 and 20.37 ± 7.88 min of active working time to manage IV and SC administrations, respectively. The infusion chair was occupied for a mean of 4.85 ± 0.91 and 0.99 ± 0.55 h during IV or SC administration, respectively. On average, considering the costs due to HCP and chair time, materials, and overhead costs, every IV and SC administration costed €80.33 and 34.90, respectively.Conclusions: In conclusion, as compared with IV administration, SC daratumumab was associated with 78%, 59%, 80% savings in terms of patient time, HCP active working time, and infusion chair, respectively, and 56.6% budget savings.

The present paper reports, to the best of our knowledge for the first time, the efficacy and tolerability of the combination of interferon (IFN)α-2a in pegylated formulation and rituximab after a “priming” phase with IFN in the frontline treatment of hairy cell leukemia (HCL) in a profoundly immunosuppressed patient with a Mycobacterium abscessus infection at onset. This immunotherapy combination may represent a potential therapeutic option in patients with active severe infection and for whom the use of purine nucleoside analogues (PNA) is contraindicated. The benefits and drawbacks of remarkably rapid immune reconstitution in the context of opportunistic infections are highlighted as well, as the potentially paradoxical effects of immune recovery as a result of effective immunotherapy strategies, known as immune reconstitution inflammatory syndrome (IRIS), have to be taken into account when dealing with patients with opportunistic infections.

Acquired isolated factor VII (FVII) deficiency is a rare but important discovery in patients with plasma cell disorders with significant therapeutic and prognostic implications. The present analysis and review of cases reported in the literature is intended to highlight disease-related characteristics associated with this rare clotting defect, clinical manifestations and outcome, and potential underlying mechanisms, and to provide guidance on how to manage these patients in terms of prophylactic and therapeutic measures. The discovery of acquired FVII deficiency in a patient with multiple myeloma (MM) or monoclonal gammopathy of uncertain significance (MGUS) should prompt an evaluation for AL amyloidosis, particularly for amyloid hepatosplenic involvement, whenever not previously documented. Acquired FVII deficiency in patients with MM and AL amyloidosis is frequently associated with severe bleeding diathesis, also related to a number of concomitant predisposing factors, adversely affecting the outcome. The prompt institution of a rapidly acting therapy is crucial to prevent severe bleeding complications and positively impact outcome. Recombinant activated factor VII (rVIIa) may represent a useful supportive care measure, both in treating active bleeding and in the peri-procedural setting. However, further clinical experience is needed to optimize the therapeutic management of this rare disorder.

Introduction: Ixazomib, lenalidomide, and dexamethasone (IRd) have been approved for the treatment of relapsed/refractory multiple myeloma (RRMM) based on the results of the TOURMALINE‐MM1.Objectives and Methods: We conducted a retrospective–prospective analysis of 106 RRMM patients (pts) treated with IRd in 21 centers in Northern Italy, with the aim to evaluate the efficacy and safety of IRd in real life.Results: At IRd initiation, 34% of pts were aged ≥75 (median 72.5), 8.5% had an ECOG performance status ≥2, 54.7% of evaluable pts carried high‐risk cytogenetic abnormalities [del17p and/or t(4;14) and/or t(14;16) and/or 1 g gain/amp], 60.2% had received ≥2 prior lines of therapy (pLoT), 57.5% were lenalidomide (Len)‐exposed (including both Len‐sensitive and Len‐refractory pts), and 22% were Len‐refractory. Main G ≥3 adverse events (AEs) were thrombocytopenia (16%) and neutropenia (12.3%). G ≥3 non‐hematologic AEs included infections (9.4%) and GI toxicity (diarrhea 5.7%, hepatotoxicity 2.8%), VTE, skin rash, and peripheral neuropathy were mainly G1‐2. The overall response rate was 56.4% (≥VGPR 30%). With a median follow‐up of 38 m, median PFS (mPFS) was 16 m and the 1‐year OS rate was 73%. By subgroup analysis, an extended PFS was observed for pts achieving ≥VGPR (mPFS 21.2 m), time from diagnosis to IRd ≥5 years (26.2 m), 1 pLoT (34.4 m), Len‐naïve (NR), age ≥70 (20 m). In pts exposed to Len, non‐refractory in any prior line and immediately prior to IRd, mPFS was 16 and 18 m, respectively. An inferior PFS was seen in Len‐refractory pts (4.6 m). By multivariate analysis, independent predictors of PFS were age ≥70 (HR 0.6), time from diagnosis ≥5 years (HR 0.32), refractoriness to Len in any prior line (HR 3.33), and immediately prior (HR 4.31).Conclusion: IRd might be effective and safe in RRMM pts with an indolent disease, in early lines of treatment, and who proved Len‐sensitive, independent of age, and cytogenetic risk.