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Background Acute kidney injury (AKI) in patients with multiple myeloma (MM) requiring renal replacement treatment (RRT) is associated with high morbidity and mortality. Early reduction of serum free light chains (FLC) using both targeted therapy against MM and intensive hemodialysis (IHD) may improve renal outcomes. We evaluated the effectiveness of two different RRT techniques on renal recovery in an MM patient population: standard dialysis procedure vs IHD with either polymethylmethacrylate (PMMA) or hemodiafiltration with endogenous reinfusion (HFR). Methods This was a multicentric retrospective study with severe AKI related to MM, between 2011 and 2018. Twenty-five consecutive patients with AKI secondary to MM requiring RRT were included. Patients that underwent IHD received six dialysis sessions per week during the first 14 days (PMMA vs HFR). All patients were diagnosed with de novo MM or first relapsed MM. Primary outcome was renal recovery defined as dialysis-free at 6 months follow-up. Results A total of 25 patients were included. Seventeen patients received IHD and eight standard dialysis. All patients were treated with targeted therapy, 84% bortezomib-based. Of the 25 patients included, 14 (56%) became dialysis independent. We observed a higher proportion of patients who received IHD in the group who recovered kidney function compared with those who remained in HD (92.9% vs 36.4%, P = .007). In our study, the use of IHD to remove FLC had a statistically significant association with renal recovery compared with the standard dialysis group (P = .024). Conclusion Early reduction of FLC with IHD as an adjuvant treatment along with MM-targeted therapy may exert a positive impact on renal recovery.

Background: Survival in multiple myeloma has improved significantly in recent years, especially in young patients. This is due to the introduction of new drugs with new mechanisms of action. We reviewed the evolution of the survival of patients with MM between 1999 and 2020 at our 12 de Octubre Hospitalinstitution. Then, to confirm our results, we used data from TriNetx, a global health research platform that includes patients from Europe and US. Methods: Using the H120 cohort, with 703 patients, we compared survival time since MM diagnosis in three groups based on age at MM diagnosis over three time periods. Comparator cohorts included 62,572 patients from US Collaborative Network and 6,377 patients from EMEA Collaborative Network. Finally, we analysed differences in the patterns of treatment between networks across the world. Kaplan‒Meier analysis was used to estimate survival probabilities,and between-group differences were tested using the log-rank test and hazard ratio. Results: For patients from H12O, the median OS was 35.61 (28.38-42.84, 95% CI), 55.59 (40.20-70.98, 95%) and 68.67 (54.92-82.42, 95%) months for the 1999-2009, 2010-2014 and 2015-2020 cohorts, respectively (p=0.0001). Among all patients included in the EMEA network, the median OS was 20.32 months vs. 34.75 months from 1999-2009 vs. 2010-2014. The median OS from the 2010-2014 vs. 2015-2020 time cohorts was 34.75 months vs. 54.43 months, respectively. In relation to the US cohort, the median OS from before 2010 vs. 2010-2014 wasnot reached in either time cohort and neither when comparing the 2010-2014 vs. 2015-2019 time cohorts. Bortezomib is the most commonly used drug in the EMEA cohort, while lenalidomide is the most commonly used drug in the US cohort. Conclusions: This large-scale study based on real-world data confirms the previous finding that MM patients have increased their survival in the last two decades.

Background: The impact of coronavirus disease 2019 (COVID-19) on hematological patients has not been comprehensively reported to date. Methods: We analyzed 39 hematological patients diagnosed with SARS-CoV-2 infection at our institution from March 7 to April 7, 2020. Clinical characteristics and outcomes were compared to a matched contemporary control group of 53 non-cancer patients hospitalized at our center. Univariate and multivariate analyses were carried out to assess the risk factors associated with poor outcome. Results: Median patient age was 64.7 years (range 36-88 years). The most frequent hematological diseases were lymphoma (30%), multiple myeloma (30%), and chronic lymphocytic leukemia (15%). On the WHO severity scale, 12.8% of the cancer patients were classified as mild, 41% as moderate, and 46.2% as severe. Most of the hematological patients were treated with hydroxychloroquine (89%) and lopinavir/ritonavir (79.5%); 51% of the patients received corticoids and 30.8% (n=12) received tocilizumab. In the multivariate analysis, we observed that only age >70 years and C reactive protein >10 mg/dl were associated with higher risk of death (odds ratio 34.86 (3.407-356.8) and 13.56 (1.28-143.45), respectively). An unfavorable impact of chemotherapy administration on COVID-19 outcome was not demonstrated. The non-hematological and hematological patients had similar clinical and laboratory characteristics; however, but mortality was higher in hematological patients (35.9% vs. 13.2%; Odds Ratio 6.5; 95% CI=1.868-23.688; P=0.003). Conclusion: Patients with hematological malignancies had a similar incidence of COVID-19, but the severity and mortality were much higher than in non-cancer patients even in the absence of therapy. Funding Statement: This work received funding from the research contract COV20/00181 from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III. Our research group was supported by the Fundacion Cris contra el cancer. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This retrospective study was approved by the Hospital Universitario 12 de Octubre Institutional Review Board (n 20/182).

Stringent complete response (sCR) is used as a deeper response category than complete response (CR) in multiple myeloma (MM) but may be of limited value in the era of minimal residual disease (MRD) testing. Here, we used 4-colour multiparametric flow cytometry (MFC) or next-generation sequencing (NGS) of immunoglobulin genes to analyse and compare the prognostic impact of sCR and MRD monitoring. We included 193 treated patients in two institutions achieving CR, for which both bone marrow aspirates and biopsies were available. We found that neither the serum free light chain ratio, clonality by immunohistochemistry (IHC) nor plasma cell bone marrow infiltration identified CR patients at distinct risk. Patients with sCR had slightly longer progression-free survival. Nevertheless, persistent clonal bone marrow disease was detectable using MFC or NGS and was associated with significantly inferior outcomes compared with MRD-negative cases. Our results confirm that sCR does not predict a different outcome and indicate that more sensitive techniques are able to identify patients with differing prognoses. We suggest that MRD categories should be implemented over sCR for the future classification of MM responses. This study was supported by grants of the Instituto de Salud Carlos III FEDER founds (Ministry of Economy and Competitivity, Madrid, Spain) FIS PI15/01484 and CRIS foundation grants 14/001 to JML. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Sí

Background: Heavily pretreated relapsed and refractory multiple myeloma (RR MM) constitutes a specific and unmet medical need. Median survival ranges from as little as 6 to 9 months, and responses to treatment are characteristically short (Richardson et al. 2007). Belantamab Mafodotin (BM), a novel anti-BCMA antibody conjugated to microtubule-disrupting agent monomethyl auristatin F, showed single-agent activity in the phase 1 DREAMM-1 and phase 2 DREAMM-2 studies in heavily pre-treated patients with RRMM (Lonial et al, 2019 & 2021). We aim to assess efficacy and safety of BM treatment administered via the expanded access compassionate care program for triple class MMRR patients in the region of Madrid (Spain). Methods: An observational, retrospective and multicenter study has been performed including all patients who received at least one dose of BM under the expanded access program in the region of Madrid (Spain) from Nov 2019 to Jun 2021. Hematology centers provided data from the medical records and entered them in a case report form distributed to the sites. Primary endpoint was overall response rate (ORR). Secondary endpoints were progression free survival (PFS), overall survival (OS) and the incidence of treatment emergent adverse events (TEAEs), with a major focus on ocular and hematologic toxicity. Results: A total of 33 patients (pts), from 14 different centers, were included from February 2020 till May 2021. Median age was 70 (46-79) years. 55% of the pts were women. Median time from diagnosis was 71 (10-858) months. 30.3% were high-risk cytogenetic features. Median of prior therapy lines was 5 (3-8) and at least 88% of the pts were triple class refractory. The median number of BM doses per patient was 3 (1-16) and the median follow-up was 11 months (95%CI 6.34-15.66). ORR was 42.2%, and 18.2% achieved ≥VGPR. Median PFS was 3 months (95%CI 0.92-5.08). Median PFS for patients who achieved ≥PR was 11 months (HR 0,26; 95% CI 0,10-0,68). No significant differences were found in PFS according to age, cytogenetic risk and prior therapy lines. OS was 424 days (95% CI 107-740). The incidence of non-hematological TEAEs was 57.6% and the most common of which was ocular toxicity (45.5%). The incidence of ≥G3 non-hematological TEAEs was 30.3%. 51.5% of the pts were diagnosed of keratopathy and 21.2% was ≥G3. 30.3% of the pts showed a reduced visual acuity, but this event was resolved in 92.9% of the pts. The most common symptoms were blurry vision (30.3%, n=10) and dry eye (24.2%, n=8). The incidence of ≥G3 hematological TEAEs was 18.2% and thrombocytopenia was the most frequent (21.2%). Dose reductions of BM were required in 30.3% of the pts and delayed in 36.4% due to TEAEs. Main causes for treatment discontinuation (81%, n=27) were disease progression (54.5%, n=18), toxicity (15.2%, n=5), death (6.1%, n=3) and due to patient's decision (3%, n=1). Conclusion: Compassionate use of BM in heavily pretreated RR MM pts showed a relevant anti-myeloma activity with a manageable safety profile.These results are similar to those observed in the DREAMM-1 and DREAMM-2 clinical trials. Disclosures No relevant conflicts of interest to declare.

Background Multiple myeloma (MM) constitutes approximately 10% of haematological malignancies, with a median age at diagnosis of 65 years. Patient survival has improved considerably over the last 20 years with the introduction of new drugs. In 1999, the first immunomodulatory drug, thalidomide, was approved, followed by lenalidomide in 2005 and pomalidomide in 2013. In 2003, proteosome inhibitors such as bortezomib were introduced and carfilzomib in 2014. In 2015, anti-CD38 monoclonal antibodies such as daratumumab were added to the treatment schemes. We have analyzed the impact on the outcome of the introduction new drugs for MM in the last 20 years in our institution. Methods A total of 862 patients diagnosed with symptomatic multiple myeloma between 1999 and 2020 in a tertiary care hospital in Spain, Hospital 12 de Octubre in Madrid, were retrospectively analysed. Survival by age was evaluated over the years, establishing three groups: 1999-2005, 2005-2015 and 2015-2020. Kaplan-Meier analysis was used for analyzing overall survival, and differences between groups were tested for statistical significance using the log-rank test. Results A total of 862 patients were included in the study. There were 409 men (47.45%) and 453 women (52.55%). The median age at diagnosis was 69 years. Among the group of patients younger than 65 years, the median survival among patients treated between the period 1999 to 2005 was 49.28 months (16.86-81.70; 95%); 78.42 months (49.83-107.01; 95%) between the years 2005 to 2015 and the median is not reached between the years 2015 to 2020 (p=0.001). Equally significantly, patients younger than 75 years have improved survival over the years. Median survival among patients treated between 1999 and 2005 was 43.43 months (23.86. 63.00; 95%); 58.80 months (43.38-74.23; 95%) between 2005 and 2015 and the median is not reached between 2015 and 2020 (p Conclusion The introduction of new agents in the treatment of multiple myeloma has transformed the natural history of the disease, achieving long survival times in younger patients. Thus, it is essential to continue to advance and develop new therapies, as has been the case in recent years with the emergence of antiBCMA therapies.