Assessment of measurable residual disease (often referred to as “minimal residual disease”) has emerged as a highly sensitive indicator of disease burden during and at the end of treatment and has been correlated with time-to-event outcomes in chronic lymphocytic leukemia. Undetectable-measurable residual disease status at the end of treatment demonstrated independent prognostic significance in chronic lymphocytic leukemia, correlating with favorable progression-free and overall survival with chemoimmunotherapy. Given its utility in evaluating depth of response, determining measurable residual disease status is now a focus of outcomes in chronic lymphocytic leukemia clinical trials. Increased adoption of measurable residual disease assessment calls for standards for nomenclature and outcomes data reporting. In addition, many basic questions have not been systematically addressed. Here, we present the work of an international, multidisciplinary, 174-member panel convened to identify critical questions on key issues pertaining to measurable residual disease in chronic lymphocytic leukemia, review evaluable data, develop unified answers in conjunction with local expert input, and provide recommendations for future studies. Recommendations are presented regarding methodology for measurable residual disease determination, assay requirements and in which tissue to assess measurable residual disease, timing and frequency of assessment, use of measurable residual disease in clinical practice versus clinical trials, and the future usefulness of measurable residual disease assessment. Nomenclature is also proposed. Adoption of these recommendations will work toward standardizing data acquisition and interpretation in future studies with new treatments with the ultimate objective of improving outcomes and curing chronic lymphocytic leukemia.
Aims: To obtain real-world data on ramucirumab use and effectiveness for the treatment of advanced gastric cancer (AGC) or gastroesophageal junction adenocarcinoma (GEJ). Methods: Observational, retrospective study carried out in 20 Spanish hospitals, in patients who started ramucirumab treatment between December 2015 and December 2018. Descriptive analysis was conducted for patient characteristics, treatment patterns and effectiveness outcomes. Results: Three hundred seventeen patients were included (93.7% treated with ramucirumab-paclitaxel and 6.3% with ramucirumab); age 62.5 (11.3) years; 66.9% male. Median progression-free survival and overall survival were 3.9 months (95% CI: 3.4–4.3) and 7.4 (95% CI: 6.4–8.9) in combination regimen and 2.0 (1.1–2.8) and 4.3 (95% CI: 1.9–7.3) in monotherapy, respectively. Conclusion: The study findings were consistent with available real-world studies and randomized clinical trials.
Introduction: Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) infection is characterised by a viral phase and a severe pro-inflammatory phase. The inhibition of the JAK/STAT pathway limits the pro-inflammatory state in moderate to severe COVID-19. Methodology: We analysed the data obtained by an observational cohort of patients with SARS-CoV-2 pneumonia treated with ruxolitinib in 22 hospitals of Mexico. The applied dose was determined based on physician’s criteria. The benefit of ruxolitinib was evaluated using the 8-points ordinal scale developed by the NIH in the ACTT1 trial. Duration of hospital stay, changes in pro-inflammatory laboratory values, mortality, and toxicity were also measured. Results: A total of 287 patients were reported at 22 sites in Mexico from March to June 2020; 80.8% received ruxolitinib 5 mg BID and 19.16% received ruxolitinib 10 mg BID plus standard of care. At beginning of treatment, 223 patients were on oxygen support and 59 on invasive ventilation. The percentage of patients on invasive ventilation was 53% in the 10 mg and 13% in the 5 mg cohort. A statistically significant improvement measured as a reduction by 2 points on the 8-point ordinal scale was described (baseline 5.39 ± 0.93, final 3.67± 2.98, p = 0.0001). There were 74 deaths. Serious adverse events were presented in 6.9% of the patients. Conclusions: Ruxolitinib appears to be safe in COVID-19 patients, with clinical benefits observed in terms of decrease in the 8-point ordinal scale and pro-inflammatory state. Further studies must be done to ensure efficacy against mortality.
Background Sarcoidosis is a multisystemic granulomatous disease of unknown origin. It is characterized by abnormal activation of lymphocytes and macrophages with the formation of granulomas. Most cases have asymptomatic pulmonary involvement. In case of symptoms, they have an excellent response to glucocorticoid therapy. We present a case of sarcoidosis with multi-organ involvement, refractory to multiple treatments including biological. Partial remission was achieved in it. Case presentation We report an interesting case of a 38-years-old Spanish woman treated by Heerfordt’s syndrome (uveitis, parotiditis, fever and facial palsy) plus pulmonary hiliar adenopathy. A sarcoidosis diagnosis was confirmed by lung biopsy. She was initially treated with an 8 weeks course of medium dose oral glucocorticoids and tapered over 8 weeks with improvement. After the suspension of glucocorticoids a relapse occurs with severe ocular involvement and suspicion of neurological involvement. The patient received multiple lines of treatment with poor response. Finally, after the combination of cyclophosphamide with infliximab, the uveitis resolved, improving the neurological symptoms. Conclusions Sarcoidosis is a benign disease in most cases. In a small percentage of cases behaves aggressively, requiring early diagnosis and immunosuppressive treatment to avoid sequelae. An adequate immunosuppressive therapy based on Anti TNF drugs should be started to minimize damage and improve the quality of life.The choice of treatment depends on the type and severity of the disease.
In patients who are or develop resistance to IM and without access to therapeutic alternatives as second generation tyrosine kinase (TKI) inhibitors or hematopoietic stem cell transplantation, the use of alkylating drugs or investigational agents is indicated. NF Kappa B pathway is constitutively activated in CML patients therefore the combination of IM with a NF Kappa β inhibitor (as thalidomide) contributes a new very interesting field of research. Thalidomide has antiproliferative activity in Hemato-oncologic diseases, therefore we decided to use in patients with CML Ph + resistant to IM with excellent results. Herein we report 14 cases of CML Ph (+): 6 males, 8 females with a median age of 38 years (19-62) treated with Imatinib (median maximum tolerated dose of 600 mg [200-800 mg/day]) plus Thalidomide 100 mg PO/day. At diagnosis (79%) were classified as high risk according with EUTOS scale. Follow up was done every month (Mo) with CBC, Hepatic and Renal Function Test and FISH test for BCR/ABL every 3 months. Median time of diagnosis 20 months (5-49); Imatinib treatment median time 20 months (3-60). The main reason to add thalidomide was lost of Cytogenetic Response (CgR) in 7, and suboptimal response in 7. Median Follow-up since Thalidomide addition 16 months (6-54 months) Table 1. Results Within the median time of follow-up all patients achieved Complete Hematologic Response. There was 9/14 (64%) Cytogenetic Responses (CgR): 7 Major CgR (4 Complete, 3 Majors), and 2 minor CgR. Five (5/14) patients (36%) do not achieve any type of response. The median time of thalidomide treatment was 12 months and median time to response 8 months (Table 2). The responses still on during follow-up and there is no lost of responses. In all cases no studies were carried out ABL mutations because lack of financial resources. Toxicity has been minimal, mainly grade 1 peripheral neurotoxicity, constipation and none had severe adverse event. Immunomodulatory drugs (thalidomide and its analogues) have several effects and do modify signals induced by receptor-ligand and include generation of Inflammatory Cytokines, anti angiogenic responses of cellular and immune adherence and antiproliferative direct effect perhaps by inhibition of transcriptional factor NF-κβ (Nuclear Factor KB) signaling, which promotes the survival of malignant cells and recognizes their activity in leukemias and myelodysplastic syndromes, therefore it is suggested as a potential therapeutic objective, immunomodulators block the activation of NF-κβ and may be a therapeutic option in CML. Our patients achieved the CyR cases of primary resistance and secondary Imatinib Resistance. As previously we reported (ASH 2012), this is the second communication of the use of Thalidomide with Imatinib with promising results, which may represent a therapeutic alternative in CML with antiproliferative enhancer and/or synergistic effect in patients with resistance to IM without opportunity of access to other treatments. Disclosures: No relevant conflicts of interest to declare.
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