Crimean-Congo hemorrhagic fever (CCHF) is a viral infectious disease for which distribution of the main vector, Hyalomma spp. ticks, is expanding. We analyzed all 10 cases of CCHF diagnosed in Spain ...during 2013-2021; case-patient median age was 56.5 years, and 7 were men. We identified CCHF virus genotypes III and V. Six case-patients acquired the infection in urban areas. Sixty percent of patients were infected in summer and 40% in spring. Two patients met criteria for hemophagocytic syndrome. Seven patients survived. The epidemiologic pattern of CCHF in Spain is based on occasional cases with an elevated mortality rate. Genotype III and, to a less extent also genotype V, CCHF circulates in humans in a common geographic area in Spain. Those data suggest that the expansion pathways are complex and may change over time. Physicians should remain alert to the possibility of new CCHF cases.
Introduction: After receiving different lines of treatment, multiple myeloma patients tend to present with less secretory and more frequent extramedullary disease. These features make treatment ...monitoring and follow-up very complex since they have to be based on the use of imaging methods and/or bone marrow aspirations or biopsies. Objective: To present the case of a patient with myeloma progressing with non-secretory bone disease and to discuss the potential impact of mass spectrometry as a new highly sensitive method able to identify the monoclonal protein (MP) in the serum of these types of patients. Materials and Methods: Informed consent was signed by the patient prior to receiving each line of treatment. The clinical information and images were obtained from anonymized electronic files. The mass spectrometry was performed with the Immunoglobulin Isotypes (GAM) assay for the mass spectrometry EXENT® Analyser Technology from Binding Site, part of Thermofisher. Results: A 73-year-old male with IgG kappa multiple myeloma progressing with a new lytic lesion after receiving 14 cycles of Talquetamab as a third line of therapy who, due to the non-secretory nature of the disease at this point, could not be enrolled in a clinical trial, thus limiting his therapeutic options. The mass spectrometry was able to identify and quantify the presence of the patient’s MP when the serum protein electrophoresis and immunofixation were still negative and therefore could have been used to confirm the progression, to permit the inclusion of the patient in a clinical trial and to further monitor the disease response. Conclusions: The higher sensitivity of the mass spectrometry methods to detect the MP in patients with myeloma and other monoclonal gammopathies translates into better identification of the disease progression, permits the inclusion of more patients in clinical trials and facilitates treatment monitoring.
Transformation of follicular lymphoma into an aggressive lymphoma (tFL) worsens the prognosis and the standard treatment is not completely defined. Allogeneic hematopoietic stem cell transplantation ...(alloSCT) could be a potentially curative option for these patients, but it has not been widely explored.
We designed a retrospective multicenter study to analyze the efficacy and toxicity of alloSCT in tFL patients and potential prognostic factors of survival.
A total of 43 patients diagnosed with tFL who underwent alloSCT in 14 Spanish centers between January 2000 and January 2019 were included. Median age was 44 (31-67) years. After a median follow-up of 58 months, estimated 5-year overall survival (OS) and progression-free survival (PFS) were both 35%. Estimated 100-day and 1-year non-relapse mortality (NRM) were 20% and 34%, respectively. The type of conditioning regimen (3-year OS of 52% vs. 20%, respectively, for reduced-intensity vs. myeloablative conditioning) and development of chronic graft versus host disease (cGVHD) (3-year OS of 75% vs. 40%) were the only factors significantly associated with OS. The only variable with an independent association with OS was cGVHD (HR, 3.4; 95% CI, 1.2-9.6).
Our results indicate that alloSCT continues to be a potentially curative option for patients with tFL.
In this randomized phase 2 study (GEM-KyCyDex), the combination of weekly carfilzomib 70 mg/m2, cyclophosphamide and dexamethasone was compared to carfilzomib and dexamethasone (Kd) in ...relapsed/refractory multiple myeloma (RRMM) after 1-3 prior lines (PLs). 197 patients were included and randomized 1:1 to receive KCd (97 patients) or Kd (100 patients) in 28-day cycles until progressive disease or unacceptable toxicity occurred. Patient median age was 70 years, and the median number of PLs was 1 (1-3). More than 90% of patients had previously been exposed to proteasome inhibitors, ≈70% to immunomodulators, and ≈50% were refractory to their last line (mainly lenalidomide) in both groups. After a median follow-up of 37 months, median progression-free survival (PFS) was 19.1 and 16.6 months in KCd and Kd, respectively (P=0.577). Of note, in the post hoc analysis of the lenalidomiderefractory population, the addition of cyclophosphamide to Kd resulted in a significant benefit in terms of PFS: 18.4 vs. 11.3 months (Hazard ratio 1.7 1.1-2.7; P=0.043). The overall response rate and the percentage of patients who achieved complete response was around 70% and 20% in both groups. The addition of cyclophosphamide to Kd did not result in any safety signal, except for severe infections (7% vs. 2%). In conclusion, the combination of cyclophosphamide with Kd 70 mg/m2 weekly does not improve outcomes as compared with Kd alone in RRMM after 1-3 PLs, but a significant benefit in PFS was observed with the triplet in the lenalidomide-refractory population. The administration of weekly carfilzomib 70 mg/m2 was safe and convenient, and, overall, the toxicity was manageable in both arms.
•CAR-Ts resulted stronger responses than BiAbs but lacked clinical significance with regards to PFS.•CAR-Ts followed by BiAbs could be 1 of the best treatment sequences for managing triple-class ...refractory myeloma.
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The efficacies of chimeric antigen receptor T cells (CAR-Ts) and bispecific monoclonal antibodies (BiAbs) for triple-class refractory (TCR) myeloma have not previously been compared, and clinical data on how to rescue patients after relapse from these immunotherapies are limited. A retrospective study of 73 TCR patients included in trials was conducted: 36 received CAR-Ts and 37 received BiAbs. CAR-Ts produced a higher overall response rate (ORR) than BiAbs (97.1% vs 56.8%, P = .002). After a median of follow-up of 18.7 months, no significant difference in progression-free survival (PFS) was observed between the CAR-T and BiAbs groups (16.6 vs 10.8 months; P = .090), whereas overall survival (OS) was significantly longer in the CAR-T than in the BiAbs group (49.2 vs 22.6 months; P = .021). BiAbs after CAR-Ts yielded a higher ORR and longer PFS2 than did nonredirecting T-cell therapies after CAR-Ts (ORR: 87.5% vs 50.0%; PFS2: 22.9 vs 12.4 months). By contrast, BiAbs after BiAbs resulted in an ORR of 33% and PFS2 of 8.4 months, which was similar to that produced by the nonredirecting T-cell therapies (ORR: 28.6%; PFS2: 8.1 months). Although this is a pooled analysis of different trials with different products and the patient profile is different for CAR-Ts and BiAbs, both were effective therapies for TCR myeloma. However, in our experience, although the PFS was similar with the 2 approaches, CAR-T therapy resulted in better OS, mainly because of the efficacy of BiAbs as rescue therapy. Our results highlight the importance of treatment sequence in real-word experience.
(1) Background: New therapeutic strategies have improved the prognosis of multiple myeloma (MM), changing the accepted view of this disease from being incurable to treatable. (2) Methods: We studied ...1001 patients with MM between 1980 and 2020, grouping patients into ten-year periods by diagnosis 1980-1990, 1991-2000, 2001-2010 and 2011-2020. (3) Results: After 65.1 months of follow-up, the median OS of the cohort was 60.3 months, and OS increased significantly over time: 22.4 months in 1980-1990, 37.4 months in 1991-2000, 61.8 months in 2001-2010 and 103.6 months in 2011-2020 (
< 0.001). Using novel agents in the front-line setting for myeloma patients yielded a significantly better OS than in those treated with conventional therapies, especially when combinations of at least two novel agents were used. The median OS of patients treated with the combination of at least two novel agents in induction was significantly prolonged compared to those treated with a single novel agent or conventional therapy in induction: 143.3 vs. 61.0 vs. 42.2 months (
< 0.001). The improvement was apparent in all patients regardless of age at diagnosis. In addition, 132 (13.2%) patients were long-term survivors (median OS ≥ 10 years). Some independent clinical predictors of long-term survival were identified: ECOG < 1, age at diagnosis ≤ 65 years, non-IgA subtype, ISS-1 and standard-risk cytogenetic. Achieving CR and undergoing ASCT were positively associated with >10 years of survival. (4) Conclusions: The combination of novel agents appears to be the main factor for the improvement in survival in MM, which is becoming a chronic and even curable disease in a subtype of patients without high-risk features.
Multiple myeloma (MM) patients with t(11;14) present unique biological features and their prognosis is not well established. We report a retrospective study of 591 MM patients, 17.3% of whom had ...t(11;14). It was designed to determine the prognostic impact of this abnormality and the effect of novel agents on the response and outcomes. Three groups were established based on their cytogenetics: (1) t(11;14); (2) high-risk chromosomal abnormalities; and (3) standard risk (SR). After 80.1 months (1.2-273.8 months) of follow-up, no differences were observed in overall survival (OS) between the t(11;14) and SR groups (75.8 vs. 87.2 months; P = 0.438). Treatment of MM t(11;14) with novel agents did not improve their overall response rate (ORR) or complete response (CR) compared with those who received conventional therapy (ORR: 87.2 vs. 79.5%, P = 0.336; CR: 23.4 vs. 12.8%, P = 0.215). This effect translated into a similar PFS (39.6 vs. 30.0 months; P = 0.450) and OS (107.6 vs. 75.7 months; P = 0.175). In summary, MM t(11;14) patients did not benefit from the introduction of novel agents as much as SR patients did, indicating that other therapies are needed to improve their outcomes.
