Infections remain a common complication in patients with multiple myeloma (MM) and are associated with morbidity and mortality. A risk score to predict the probability of early severe infection could help to identify the patients that would benefit from preventive measures. We undertook a post hoc analysis of infections in four clinical trials from the Spanish Myeloma Group, involving a total of 1347 patients (847 transplant candidates). Regarding the GEM2010 > 65 trial, antibiotic prophylaxis was mandatory, so we excluded it from the final analysis. The incidence of severe infection episodes within the first 6 months was 13.8%, and majority of the patients experiencing the first episode before 4 months (11.1%). 1.2% of patients died because of infections within the first 6 months (1% before 4 months). Variables associated with increased risk of severe infection in the first 4 months included serum albumin ≤30 g/L, ECOG > 1, male sex, and non-IgA type MM. A simple risk score with these variables facilitated the identification of three risk groups with different probabilities of severe infection within the first 4 months: low-risk (score 0–2) 8.2%; intermediate-risk (score 3) 19.2%; and high-risk (score 4) 28.3%. Patients with intermediate/high risk could be candidates for prophylactic antibiotic therapies.

No abstract

Background:Early phase clinical trials (phases I / II) represent a key element in the process of translation of knowledge, obtained in basic research, towards its application in clinical practice. Phase I studies are designed to evaluate the drug's safety and toxicity at different dose levels and determine drug pharmacokinetics and pharmacodynamics. In contrast, phase II trials focus on clinical effectiveness. In some cases, phase I studies are perceived as a high risk procedure for the achievement of an uncertain benefit.Therefore, it seems appropriate to perform an analysis of the results obtained in early stage trials, in order to achieve a more objective risk/benefit assessment in this context.Aims:The main objective of the study was to analyze the safety and benefit of clinical trials in early stages in hematology. The results of overall survival (OS), progression free survival (PFS) and major toxicities between the phase I and phase II trials were compared.Methods:Data was extracted from medical histories of 262 patients with different hematological pathologies. These patients were admitted within one of the 66 phase I / II clinical trials opened between 2011 and 2018 at the Hospital 12 de Octubre. Data obtained was analyzed in terms of clinical response, toxicity and survival. We excluded 39 cases due to screening failure and 1 case due to withdrawal of the informed consent.Results:Considering the whole sample of patients, both in phase I (n = 77) and in phase II (n = 145), an overall response rate was verified (including complete and partial responses) in 66% of the patients. In 24% the disease remained stable and in 10% of cases it was refractory. The discontinuation rate of the studies in the whole series was 35.5%, mainly due to progression of the disease.Overall survival (OS) was 34.6 months, while the progression‐free survival (PFS) was 31.6 months. There were significant differences in PFS between the group of patients in phase I (22.5 months) and phase II (35.7 months) (p = 0.004), but there were no differences in OS (p = 0.405). 33,7% and 32,4% of patients enrolled in phase I and phase II studies died, respectively. The main cause of death was progression.Up to 39% of the patients included had some type of grade 3 or 4 toxicity, being hematological toxicity the most frequent(up to one third of the patients). In this regard, there were no significant differences between phase I and phase II trials, with 32.5% and 26.2% grade 3 or 4 toxicity, respectively.Summary/Conclusion:When comparing phase I and phase II trials, we found a higher PFS in phase II studies. This difference is probably due to the fact that part of the patients in phase I trials have received suboptimal doses of treatment, as the main objective of these studies is to warrant safety. However, when analyzing safety data, the differences between both groups in terms of grade 3 or higher toxicity are minimal and not statistically significant. In addition, there were no differences of OS between phase I and II trials.imageThere are few reports in this regard that can be used as a reference. However, the results obtained in our center offer a hopeful outlook in the future of therapeutics in Hematology, confirming the existence of a significant clinical benefit in patients included in early phase clinical trials.

We report a case of coronavirus disease 2019 (COVID-19) reactivation in a 52-year-old man with diagnosis of multiple myeloma (MM) of immunoglobulin G (IgG) kappa subtype, with a previously resolved COVID-19 who received a salvage regimen of carfilzomib, daratumumab and dexamethasone. He was admitted to the hospital with COVID-19. He presented with fever, diarrhea, dry cough and dyspnea, and a chest X-ray showed bilateral pneumonia suggestive of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which was confirmed by real-time polymerase chain reaction (RT-PCR) on a nasopharyngeal sample. Analytical findings revealed an elevation of inflammatory parameters and severe lymphopenia. The patient was treated with oral hydroxychloroquine, oral ritonavir/lopinavir, low-molecular-weight heparin and ceftriaxone, high dose of oral corticosteroids, a single dose of tocilizumab and remdesivir within the clinical trial. Subsequently, the patient showed a satisfactory clinical evolution with resolution of the symptoms and normalization of analytical parameters, and the SARS-CoV-2 RT-PCR test became negative. He received the second dose of carfilzomib and the first dose of daratumumab. Five days after, he was re-admitted to the hospital with a reactivation of COVID-19. A second dose of tocilizumab was administered, as well as hyperimmune plasma as compassionate use. Two days later, he presented with clinical worsening requiring admission to the intensive care unit leading to a fatal outcome. Based on the clinical evolution of the disease, we suggest that daratumumab and carfilzomib treatment could be related to the reactivation of COVID-19. To our knowledge, this is the first case regarding COVID-19 reactivation after any treatment. In this scenario, hematologists need to carefully weigh the risks and benefits before planning chemotherapy treatments.