BackgroundThe anti-CD38 monoclonal antibody daratumumab is approved as a single agent for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who received at least three prior lines of therapy, including proteasome inhibitor and immunomodulatory agent. A retrospective multicentric study was designed to evaluate feasibility, tolerability, and efficacy of daratumumab in monotherapy in RRMM.MethodsThis study included 44 consecutive RRMM patients that underwent daratumumab monotherapy after a median number of four prior therapies (range 2–9). Patients were treated in seven Sicilian centers, as part of Sicilian Myeloma Network and three Calabrian centers outside of controlled clinical trials from August 2016 through July 2020.ResultsThe regimen was well tolerated with few grade 3–4 haematological and rare non-haematological adverse events, such as pneumonia. Definitive discontinuation was due to disease progression in 25 (57%) patients. Since three patients did not complete at least one full cycle, a total of 41 patients was evaluated for response. Overall response rate was 37%, and the disease control rate (stable disease or better) was high (73%). The best achieved responses within 6 months were very good partial remission or better (27%), partial remission (10%), minimal response (14%) and stable disease (22%). After a median follow up of 7.8 months, median progression free survival (PFS) was 7.2 months and overall survival (OS) 7.8 months. Univariate analysis showed that patients with PR or better after 6 months of therapy had longer median PFS and OS (respectively 29.5 vs 3.6 months, p=0.0001 and 30.6 vs 3.9 months p=0.0001), confirmed by multivariate analysis. Furthermore, standard cytogenetic risk and biochemical relapse type had prolonged median PFS, but not OS (respectively unreached vs 2.6, p=0.03 and 23.9 vs 6.2, p=0.05) in both univariate and multivariate analysis. Additionally, univariate analysis showed that patients treated with carfilzomib-lenalidomide-dexamethasone prior to daratumumab had significantly shorter PFS compared to pomalidomide-dexamethasone (3.4 months vs 9.3 months, p=0.03), that multivariate analysis failed to confirm.ConclusionsOur findings indicate that daratumumab as single agent is safe and well-tolerated regimen in real-life, associated to prolonged PFS and OS in responding patients. No new safety signals were identified.

IntroductionPatients with multiple myeloma (MM) frequently reported immune impairment with an increased risk for infection-related mortality. We aimed to evaluate the immune response in MM patients vaccinated for SARS-CoV-2 during active treatment.MethodsWe enrolled 158 patients affected by active MM or smoldering MM (SMM) and 40 healthy subjects. All subjects received 2 or 3 doses of the BNT162b2 (Pfizer/BioNTech) vaccine, and the anti-spike IgG values were evaluated after every dose. We applied the Propensity Score Matching (PSM) as a consequence of the limited sample size and its heterogeneity to adjust for differences in baseline clinical variables between MM patients who achieved or not a vaccine response after 2 or 3 doses.ResultsAt 30 days from the second dose, the median antibodies level in MM was 25.2 AU/mL, lower than in SMM and in the control group. The same results were confirmed after the third dose, with lower median anti-spike IgG levels in MM, compared to SMM and control group. Following PSM, lack of response to SARS-CoV-2 complete vaccination plus boost was associated with age more than 70 years old and use of high-dose of steroids. We failed to identify an association between specific treatment types and reduced vaccine response. The use of prophylaxis with tixagevimab/cilgavimab for 40 non-responder patients after 3 doses of vaccine has proven to be an effective and safe approach in reducing the risk of serious illness in the event of a breakthrough SARS-CoV-2 infection, faced with a mild symptomatic course, and in providing protection instead of long-term humoral immune vaccine responses. Following PSM, only the high-risk cytogenetic abnormalities were associated with an increased risk of developing a breakthrough SARS-CoV-2 infection.ConclusionMonitoring the immune response is fundamental in MM patients that remain highly vulnerable to SARS-CoV-2 despite the vaccine. The use of prophylaxis with tixagevimab/cilgavimab can guarantee better protection from the severe form of the disease.

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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.