Clinical course and risk factors for mortality from COVID-19 in patients with haematological malignancies.

BACKGROUND: The impact of coronavirus disease 2019 (COVID-19) in haematological patients (HP) has not been comprehensively reported. METHODS: We analysed 39 patients with SARS-CoV-2 infection and haematological malignancies. Clinical characteristics and outcomes were compared to a matched control group of 53 non-cancer patients with COVID-19. Univariate and multivariate analyses were carried out to assess the risk factors associated with poor outcome. RESULTS: The most frequent haematological diseases were lymphoma (30%) and multiple myeloma (30%). Eighty-seven % HP developed moderate or severe disease. Patients with haematological malignancies had a significantly higher mortality rate compared to non-cancer patients (35.9% vs 13.2%; P = .003 (odds ratio 6.652). The worst outcome was observed in chronic lymphocytic leukaemia patients. Only age >70 years and C reactive protein >10 mg/dl at admission were associated with higher risk of death (odds ratio 34.86, P = .003 and 13.56,P = .03). Persistent viral sheddind was detected in 5 HP. Active chemotherapy, viral load at diagnosis and COVID-19 therapy were not predictors of outcome. CONCLUSION: Mortality of COVID-19 is significantly higher in patients with haematological malignancies compared to non-cancer patients. The impact of persistent viral shedding must be considered in order to re-start therapies and maintain infectious control measures.

Impact of IPSS-M implementation in real-life clinical practice.

Objectives: The IPSS-M is a recently published score for risk stratification in myelodysplastic syndromes (MDS), based on clinical and molecular data. We aimed to evaluate its relevance on treatment choice in a real-life setting. Methods: We retrospectively collected clinical, cytogenetic and molecular data from 166 MDS patients. We calculated IPSS-R and IPSS-M scores and compared Overall Survival (OS) and Leukemia Free Survival (LFS). We also analyzed which patients would have been affected by the re-stratification in terms of clinical management. Results: We found that 86.1% of the patients had at least one genetic alteration. The most frequent mutated genes were SF3B1 (25.9%), DNMT3A (16.8%) and ASXL1 (14.4%). IPSS-M re-stratified 48.2% of the patients, of which 16.9% were downgraded and 31.3% were upgraded. IPSS-M improved outcome prediction, with a Harrell's c-index of 0.680 vs 0.626 for OS and 0.801 vs 0.757 for LFS. In 22.2% of the cohort, the reclassification of the IPSS-M could potentially affect clinical management; 17.4% of the patients would be eligible for treatment intensification and 4.8% for treatment reduction. Conclusions: IPSS-M implementation in clinical practice could imply different treatment approaches in a significant number of patients. Our work validates IPSS-M in an external cohort and confirms its applicability in a real-life setting.

Octogenarians with chronic kidney disease in the nephrology clinic: Progressors vs. non-progressors.

Background: The current definition of chronic kidney disease applied to patients over the age of 80 has increased the number of referrals to Nephrology. However not all of these patients may benefit from its assessment. This study aims to analyze the evolution of ≥80 years old patients referred to Nephrology. Methods: Single-center study including patients ≥80 years old with eGFR <60 mL/min/1,73m2 who were referred to Nephrology consultation for the first time. Clinical and analytical parameters were collected retrospectively 12 months before the visit, and prospectively at baseline, and 12 and 24 months after the initial visit. We divided patients into two groups based on annual eGFR loss: progressors (>5 mL/min/1.73m2) and non-progressors (≤5 mL/min/1,73m2). Results: A total of 318 patients were included, mean age was 84,9 ± 4 (80-97) years. Baseline serum creatinine was 1,65 ± 0,62 mg/dL, eGRF 35 (28-42) mL/min/1,73, and albumin/creatinine ratio 36 (7-229) mg/g. 55,7% of the patients met the definition of progressor at baseline (initial-progressors), 26,3% were progressors after a 12-month follow-up and 13,4% after 24 months. 21,2% and 11,4% of initial-progressors met this definition at 12 and 24 month follow up. The main risk factor for progression was albuminuria. No relationship was found between the nephrologist intervention and the evolution of renal function among initial non-progressors. Conclusion: Elderly patients who have stable renal function at the time of referral will continue to have stable renal function over the subsequent 24 months and thus may not need to be referred to a nephrologist.

Clinical Outcomes of Patients with Multiple Myeloma after Daratumumab Failure.

Anti-CD38 monoclonal antibody (MoAB) therapy has significantly improved the prognosis of patients with multiple myeloma. However, not all patients sustain durable responses. We aimed to describe the natural history of patients relapsed or refractory (R/R) to CD38 MoAB therapy. We performed a single-center, retrospective analysis of the clinical characteristics and outcomes of 81 patients with multiple myeloma who progressed after treatment with daratumumab. Our cohort was heavily pretreated, with a median of two lines prior to daratumumab and only 17 patients received daratumumab as a first line. A total of 38.2% had received a previous autologous stem cell transplantation (ASCT), and 61.7% had received both an immunomodulatory drug (IMID) and a proteasome inhibitor (PI). The median overall survival (OS) was 21 months for the global cohort but it decreased to 14 months for triple-class refractory patients and 5 months for penta-refractory patients. Most of the patients (83.9%) received treatment after daratumumab progression, in many cases with second generation IMID or PI, but seven patients were treated with anti-BCMA therapy and three patients received CART therapy within a clinical trial. In conclusion, patients R/R to daratumumab represent an unmet clinical need with poor prognosis and in need of incorporation of new treatments.

Ibrutinib effect in acquired von Willebrand syndrome secondary to Waldenström macroglobulinemia.

The pathological increase of clonal IgM in Waldenström macroglobulinemia can be associated with acquired von Willebrand syndrome and can be a major risk of bleeding symptoms in this subgroup of patients with Waldenström macroglobulinemia. The Bruton tyrosine kinase inhibitor ibrutinib is one of the approved treatments for symptomatic Waldenström macroglobulinemia. However, some controversy exists regarding the use of ibrutinib in these patients with high risk of bleeding because of its antiaggregant effect that could increase the risk of bleeding. Here, we present the case of a patient with Waldenström macroglobulinemia with associated acquired von Willebrand syndrome and progressively significant bleeding symptoms, who experienced a rapid increase in von Willebrand factor with ibrutinib treatment, despite only reaching a partial response in IgM levels similar to those reached with other previous treatments. We suggest that the control over the monoclonal protein is not the only mechanism that explains the good response, improvement in the bleeding symptoms and von Willebrand factor levels. This fact could be explained by the reduced glycoprotein Ib receptor expression induced by ibrutinib and the consequent von Willebrand factor increase in peripheral blood.

Making clinical decisions based on measurable residual disease improves the outcome in multiple myeloma.

The assessment of measurable residual disease (MRD) in bone marrow has proven of prognostic relevance in patients with multiple myeloma (MM). Nevertheless, and unlike other hematologic malignancies, the use of MRD results to make clinical decisions in MM has been underexplored to date. In this retrospective study, we present the results from a multinational and multicenter series of 400 patients with MRD monitoring during front-line therapy with the aim of exploring how clinical decisions made based on those MRD results affected outcomes. As expected, achievement of MRD negativity at any point was associated with improved PFS versus persistent MRD positivity (median PFS 104 vs. 45 months, p < 0.0001). In addition, however, 67 out of 400 patients underwent a clinical decision (treatment discontinuation, intensification or initiation of a new therapy) based on MRD results. Those patients in whom a treatment change was made showed a prolonged PFS in comparison with those 333 patients in which MRD results were not acted upon (respectively, mPFS 104 vs. 62 months, p = 0.005). In patients who achieved MRD negativity during maintenance (n = 186) on at least one occasion, stopping therapy in 24 patients vs. continuing in 162 did not alter PFS (mPFS 120 months vs. 82 months, p = 0.1). Most importantly, however, in patients with a positive MRD during maintenance (n = 214), a clinical decision (either intensification or change of therapy) (n = 43) resulted in better PFS compared to patients in whom no adjustment was made (n = 171) (mPFS NA vs. 39 months, p = 0.02). Interestingly, there were no significant differences when MRD was assessed by flow cytometry or by next-generation sequencing. Herein, we find that MRD is useful in guiding clinical decisions during initial therapy and has a positive impact on PFS in MM patients. This potentially opens a new dimension for the use of MRD in MM, but this role still remains to be confirmed in prospective, randomized clinical trials.