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Background Current randomized controlled trials are investigating the efficacy and safety of mechanical thrombectomy (MT) in patients with medium vessel occlusion (MeVO) stroke. Whether best medical management (MM) is more efficient than unsuccessful vessel recanalization during MT remains unknown. Methods This was a retrospective cohort study using data from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021. Only patients with occlusion of the distal branches (M2 and M3) of the middle cerebral artery territory were included. Unsuccessful MT was defined as a modified Thrombolysis in Cerebral Infarction score of 0–2a. Propensity score matching was used to control for confounders. The primary outcome was functional independence, defined as a modified Rankin Scale (mRS) score of 0–2 at 90 days after treatment. Multivariable regression analysis was used to assess factors associated with the primary outcome. Results Of 2903 patients screened for eligibility, 532 patients were analyzed (266 per group) after propensity score matching. The MM group had superior functional outcomes, with 32% achieving mRS 0–1 at 90 days compared with 21% in the MT group (P=0.011). Patients in the MM group also had significantly lower rates of symptomatic intracranial hemorrhage (sICH) (3.4% vs 16%, P<0.001) and any hemorrhage (18% vs 48%, P<0.001). On multivariable regression, unsuccessful MT was associated with reduced odds of functional independence (OR 0.50, 95% CI 0.29 to 0.85, P=0.011) and increased odds of sICH (OR 4.32, 95% CI 1.84 to 10.10, P<0.001). Mortality rates were similar between groups (27% in MM vs 29% in MT, P=0.73). Conclusion Unsuccessful MT for MeVO was linked to worse outcomes than best MM. These findings highlight the risks of prolonged attempts and emphasize the importance of efficient procedural decision-making to reduce complications and improve patient outcomes.

Importance There is a lack of long-term efficacy and safety data on hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) and on RNA interference (RNAi) therapeutics in general. This study presents the longest-term data to date on patisiran for hATTR-PN. Objective To present the long-term efficacy and safety of patisiran in adults with hATTR-PN. Design, Setting, and Participants This global open-label extension (OLE) of the APOLLO randomized clinical trial and phase 2 OLE study enrolled patients from 43 hospitals or clinical centers across 19 countries between July 2015 and August 2017, with follow-up until November 2022. Of 212 eligible patients with hATTR who completed the phase 3 APOLLO or phase 2 OLE parent studies, 211 enrolled in and 138 completed the global OLE. Intervention Patisiran, 0.3 mg/kg, intravenously once every 3 weeks for up to 5 years. Main Outcomes and Measures Outcomes evaluated at year 5 of the global OLE included disability (polyneuropathy disability [PND] score); polyneuropathy severity (Neuropathy Impairment Score [NIS]), nutritional status (modified body mass index [mBMI]), quality of life (Norfolk Quality of Life–Diabetic Neuropathy [Norfolk QOL-DN]), and Rasch-Built Overall Disability Scale (R-ODS), with no statistical hierarchy. Safety, survival probability, and mortality were also assessed. Results At the global OLE baseline, the mean (SD) age was 61.3 (12.3) years, and 156 patients (73.9%) were male. In 138 patients completing the study, PND scores remained stable or improved in 89 patients (65.0%), NISs showed a mean (SD) change of 10.9 (14.7), and mean (SD) mBMI (calculated as weight in kilograms divided by height in meters squared times serum albumin in grams per liter) increased by 46.4 (120.7) over 5 years from baseline. Norfolk QOL-DN and R-ODS scores showed mean (SD) changes of 4.1 (16.7) and –3.7 (6.2), respectively. Adverse events (AEs) leading to study withdrawal occurred in 47 patients (22.3%). Infusion-related reactions were the most common treatment-related AE (n = 34 [16.1%]). Overall, 41 patients (19.4%) died during the study. Patisiran treatment in the parent study and low familial amyloid polyneuropathy score at parent study baseline were associated with significantly improved survival. Conclusions and Relevance In the longest study of an RNAi therapeutic for any disease, patisiran treatment resulted in modest changes for patients with hATTR-PN with an acceptable safety profile. These results highlight the importance of initiating early treatment for hATTR and the potential of RNAi therapeutics in medicine. Trial Registration ClinicalTrials.gov Identifier: NCT02510261

Abstract Cardiovascular disease remains a prominent cause of disability and premature death worldwide. Within this spectrum, carotid artery atherosclerosis is a complex and multifaceted condition, and a prominent precursor of acute ischaemic stroke and other cardiovascular events. The intricate interplay among inflammation, oxidative stress, endothelial dysfunction, lipid metabolism, and immune responses participates in the development of lesions, leading to luminal stenosis and potential plaque instability. Even non-stenotic plaques can precipitate a sudden cerebrovascular event, regardless of the degree of luminal encroachment. In this context, carotid imaging modalities have proved their efficacy in providing in vivo characterization of plaque features, contributing substantially to patient risk stratification and clinical management. This review emphasizes the importance of identifying high-risk individuals by use of current imaging modalities, biomarkers, and risk stratification tools. Such approaches inform early intervention and the implementation of personalized therapeutic strategies, ultimately enhancing patient outcomes in the realm of cardiovascular disease management.

Objectives To reassess the role of primary retroperitoneal lymph node dissection (RPLND) in patients with marker‐negative non‐seminomatous germ cell tumour (NSGCT) clinical stage (CS) 2a, to explore results in patients with CS 2b and to evaluate surgical methods, recurrence, and adjuvant chemotherapy indications. Materials and Methods Data from 17 institutions were collected, comprising 305 men who underwent primary RPLND for CS 2 NSGCT. Regression analyses were conducted to predict histology in the RPLND specimen and disease‐free survival (DFS). Results A larger retroperitoneal lymph node diameter was associated with pure teratoma in the RPLND specimen (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01–1.07; P = 0.03), but no association was observed with DFS. The 5‐year DFS rates in marker negative CS 2a and 2b were 79% and 76%. In men with non‐teratomatous viable cancer in the RPLND specimen, the 5‐year DFS rates for CS 2a and 2b were 95% and 87% with adjuvant chemotherapy, and 67% and 74% without adjuvant chemotherapy. We did not identify an association between the number of adjuvant chemotherapy cycles and DFS. Conclusions Our study suggests considering primary RPLND not only in marker‐negative CS 2a but also in CS 2b. Further research should determine the efficacy of primary RPLND in men with CS 2c and marker‐positive CS 2, as well as which patients may benefit from adjuvant chemotherapy and the optimal cycle number.

Endoscopic ultrasound (EUS)-guided tissue sampling includes the techniques of fine needle aspiration (FNA) and fine needle biopsy (FNB), and both procedures have revolutionized specimen collection from the gastrointestinal tract, especially from remote/inaccessible organs. EUS-FNB has replaced FNA as the procedure of choice for tissue acquisition in solid pancreatic lesions (SPLs) across various society guidelines. FNB specimens provide a larger histological tissue core (preserving tissue architecture) with fewer needle passes, and this is extremely relevant in today’s era of precision and personalized molecular medicine. Innovations in needle tip design are constantly under development to maximize diagnostic accuracy by enhancing histological sampling capabilities. But, apart from the basic framework of the needle, various other factors play a role that influence diagnostic outcomes, namely, sampling techniques (fanning, aspiration or suction, and number of passes), collection methods, on-site evaluation (rapid, macroscopic, or visual), and specimen processing. The choice taken depends strongly on the endoscopist’s preference, available resources at the disposal, and procedure objectives. Hence, in this review, we explicate in detail the concepts and available literature at our disposal on the topic of EUS-guided pancreatic tissue sampling to best guide any practicing gastroenterologist/endoscopist in a not-to-ideal set-up, which EUS-guided tissue acquisition technique is the “best” for their case to augment their diagnostic outcomes.

Background: Positron emission tomography (PET) scan is the imaging modality of choice for initial staging and response assessment of follicular lymphoma (FL). Quantitative parameters such as standardized uptake value (SUV) have been investigated as putative prognosticators in FL, with high baseline SUVmax predicting aggressive disease. To date, there is no data to guide treatment choices in patients (pts) with high SUVmax but with no documented evidence of histologic transformation (HT). Specifically, it remains unclear whether anthracycline-containing regimens, such as R-CHOP, are more beneficial than R-Bendamustine (BR) in these pts. Therefore, we aimed to compare the efficacy of frontline R-CHOP and BR in newly diagnosed FL pts based on the SUVmax at baseline PET (bPET). Patients and Methods: Pts with newly diagnosed, biopsy-proven FL1-2 and FL3A who had a bPET scan and who received either first-line R-CHOP or BR within 6 months of diagnosis between 2002 and 2022 were evaluated. Analysis was restricted to pts with age &lt; 70 years to reduce confounding of age with treatment selection. Cohorts included were the FOLL12 (n=562, Luminari et al JCO 2022) and the R-chemotherapy arm of the RELEVANCE (n=216, Morschhauser et al NEJM 2018) clinical trials, the prospectively enrolled Molecular Epidemiology Resource (MER) and the Lymphoma Epidemiology of Outcomes (LEO) cohorts (n=288) and a retrospective cohort from 13 Australian centers (n=219). Choice of chemotherapy regimen was per treating physician. Maintenance was per protocol (FOLL12/RELEVANCE) or per treating physician (MER/LEO/Australia). Event-free survival (EFS) and overall survival (OS) were defined as time from treatment initiation to progression, relapse, retreatment or death; both were censored at 72 months due to varying follow-up across cohorts. SUVmax was grouped by tertile within each cohort to account for potential differences in SUVmax distributions and patient populations across cohorts. Kaplan Meier curves and multivariable Cox models cohort-stratified and adjusted for clinical factors (FLIPI, ECOG PS, age, grade 3A) were used to evaluate outcomes. Results: The median age at diagnosis was 57 years (IQR 49-64). 651 (51%) pts were treated with R-CHOP and 634 (49%) with BR. Within the study cohorts, there was a prevalence of cases receiving BR compared to R-CHOP in the Australian (90% vs 10%) and MER/LEO (68% vs 32%) cohorts, while the opposite was observed in the RELEVANCE (16% vs 84%) and FOLL12 (37% vs 63; p&lt;0.001) trials. Pts receiving R-CHOP were slightly younger (median 56 vs 58 years, p=0.005), more frequently had grade 3A (17% vs 7%, p&lt;0.001), elevated LDH (27% vs 22%, p=0.029), bulky disease &gt; 7 cm (44% vs 37%, p=0.019), lower ECOG PS (PS &gt;1 7% vs 13%, p&lt;0.001), and higher rate of high risk FLIPI (37% vs 30%, p=0.005). Baseline SUVmax was slightly lower in R-CHOP (median 10.7, IQR 7.9-14.9) vs BR (median 11.0, IQR 8.2-14.2) treated pts (p=0.0045). At a median follow-up of 56 months (range, 1-72 months), 415 pts (32%) had an event and 103 (8%) died. Higher SUVmax was not associated with EFS (middle tertile HR=0.96, 95% CI 0.76-1.22; upper tertile HR=0.86, 95% CI 0.68-1.09; p=0.45) or OS (middle tertile HR=1.28, 95% CI 0.80-2.05; upper tertile HR=0.97, 95% CI 0.59-1.59; p=0.44) in multivariable models stratified on cohort and adjusted for treatment and clinical factors. We then compared outcomes by treatment within tertiles of SUVmax. In multivariable models, R-CHOP had modestly inferior EFS to BR in low (HR=1.27, 95% CI 0.84-1.93) and middle tertiles (HR=1.49, 95% CI 0.99-2.25), and modestly superior OS to BR in low (HR=0.59, 95% CI 0.23-1.47) and middle (HR=0.79, 95% CI 0.37-1.71) tertiles. Both EFS (HR=1.06, 95% CI 0.71-1.58) and OS (HR=1.02, 95% CI 0.45-2.30) for R-CHOP were similar to BR in the highest tertile. No comparisons identified a statistically significant benefit for either therapy in multivariable models when evaluating SUVmax tertile subsets. Conclusions: In this large multicenter study of newly diagnosed FL pts with bPET who received frontline immunochemotherapy, higher baseline SUVmax was not associated with inferior outcomes after adjusting for treatment and clinical factors. Within the caveats of retrospective studies and confounding of treatment selection, these data provide no clear insights for SUVmax-based therapy selection in first-line follicular lymphoma pts treated with immunochemotherapy.

Introduction The International Prognostic Scoring System (IPSS) and its revised version (IPSS-R) were developed using datasets from patients (pts) with untreated MDS. The cytogenetic risk groups used in IPSS-R were expanded to 5 groups from the 3 used in IPSS. Among the new groups introduced in IPSS-R is the “very complex” karyotype (VCK) where ≥4 karyotypic abnormalities are seen compared to “complex karyotype (CK)” with only 3 abnormalities. However, the prognostic impact of VCK vs CK, as well as individual cytogenetic abnormalities and TP53 mutation (TP53mut) status within the CK and VCK subgroups in pts with MDS treated with hypomethylating agents (HMAs) has not been well studied. Hence, we analyzed these questions in a large cohort of HMA-treated MDS pts in the icMDS VALIDATE database. Methods The icMDS VALIDATE database contains MDS pts treated with frontline HMA monotherapy or HMA-based combinations from 22 specialized international centers. Pts with unknown HMA type, date of HMA initiation, missing age, missing sex, missing cytogenetic data, bone marrow or peripheral blood blasts ≥20%, or missing survival status were excluded. We performed time-to-event analyses using the Kaplan-Meier method and compared groups by the log-rank test. We measured overall survival (OS) from time of HMA initiation. VALIDATE protocol was exempted, acknowledged, or approved by all centers' IRBs. VALIDATE is supported by an independent grant from Abbvie. Results A total of 1940 pts were included. Median age was 70 (range: 18-99) years and 66% were men. According to IPSS-R cytogenetic risk groups, 1.9% (37) were very good, 43.4% (841) good, 15.5% (301) intermediate, 11.6% (226) poor, and 27.6% (535) very poor. By HMA type, 71% of pts were treated with azacitidine, 14% with decitabine, 6% with HMA and venetoclax, and 9% with another HMA combination. Approximately 28% of pts underwent allogeneic hematopoietic stem cell transplant (alloHSCT). The IPSS-R cytogenetic risk groups had different OS (p&lt;0.001)with median OS (mOS; months [mo], 95% CI) as follows: very good (43.4, 34.7-72.5), good (41.7, 36.4-46.8), intermediate (24.5, 23.1-32.4), poor (24.2, 19.2-28.5), and very poor (13.6, 12.5-14.5). The difference remained significant (p=0.001) after censoring at time of alloHSCT with mOS as follows: very good (40.4, 23.2-64.3), good (24.3, 22.2-26.3), intermediate (19.3, 15.1-22.2), poor (12.2, 10.3-14.8), and very poor (9.1, 8.2-19.7). Interestingly, the difference between mOS for intermediate and poor risk cytogenetics became more apparent after censoring at time of alloHSCT. Next, we compared the outcomes of pts with CK and VCK to non-complex karyotype (NCK) MDS. The mOS for pts with VCK MDS (13.6 mo, 12.5-14.5) was worse compared to pts with CK (19.9 mo, 19.9-16.8; p=0.004) and NCK (36.1 mo, 32.7-37.8; p&lt;0.001) MDS. Among the 1458 pts with available molecular data, more pts with VCK (75%, 330) MDS had a concurrent TP53mut compared to pts with CK (40%, 21; p&lt;0.001) and NCK (7%, 64 p&lt;0.001) MDS. Considering only patients with TP53mut MDS, mOS for pts with VCK (12.2, 11.1-13.9) was worse compared with NCK (24.2, 16-1-53.1; p&lt;0.001) but not with CK (19.9, 9.5-NR; p=0.9); the difference between CK and NCK was not significant (p=0.16). Among pts with TP53 wildtype (TP53WT) MDS, VCK (15.0, 13.2-18.2) had a similar mOS to TP53WT CK (18.8, 12.6-41.1; p=0.19) while both groups had worse mOS compared to TP53WT NCK (33.4, 30.1-37.0) (p=0.01). In a survival analysis of 616 pts with MDS with ≥3 cytogenetic abnormalities, -17/del(17p) (12.8 mo; p=0.009), inv(3)/t(3q)/del(3q) (10.9 mo; p=0.006), and del(7q) (12.1mo; p=0.024), though not -7 (12.6mo; p=0.23), were associated with lower mOS compared to the pts with MDS without these abnormalities (14.3mo). Conclusions Using one of the largest databases of HMA-treated MDS pts, we show that IPSS-R cytogenetic risk categories associate with significantly different survivals among HMA-treated MDS pts, even after censoring at time of alloHSCT. Importantly, VCK MDS was associated with worse mOS compared to CK and NCK MDS but not in pts with a concurrent TP53mut. Among pts with MDS with ≥3 chromosomal abnormalities, having -17/del(17p), inv(3)/t(3q)/del(3q), or del(7q) was associated with worse survival.

Background Follicular lymphoma (FL) is a generally indolent disease where a watch and wait strategy is standard in asymptomatic patients (pts) with a low tumor-burden. Harnessing antitumor immunity through an anti-tumor immunization strategy at this stage may delay or avoid the subsequent need for more toxic and complex therapies. EO2463 is a therapeutic vaccine designed from non-self protein sequences, derived from gut bacteria, including 4 HLA-A2 synthetically produced 9-mer CD8 cytotoxic T cell epitopes, exhibiting molecular mimicry with specific epitopes on the B cell markers CD20, CD22, CD37, and CD268 (BAFF-receptor). Additionally, EO2463 contains a CD4 helper epitope UCP2 derived from hTERT. The compound expands pre-existing memory CD8 T cells recognizing the non-self protein sequences from gut bacteria which can then cross-react with the selected B cell antigens on tumor cells. EO2463 is being used to drive anti-tumor immunity against B cell malignancies, and has demonstrated long-lasting, specific CD8-memory T cell responses and clinical activity in relapsed/refractory FL and marginal zone lymphoma (MZL) [J Clinical Oncol 2024, 42 (S16), 7058]. Furthermore, CD8 T cells expanded from samples of patients treated with EO2463 can kill HLA-A2 expressing lymphoblastoid cell lines presenting the B cell targets [Hematological Oncol 2023, 41 (S2), 581-582]. Methods The current report describes Cohort 2 of trial EONHL1-20/SIDNEY (NCT04669171) and includes pts with newly diagnosed, previously untreated FL, grade 1-3A, HLA-A2, and not in need of treatment. Pts receive EO2463 (300μg/peptide) SC with adjuvant Montanide ISA 51 VG, q2 weeks (w) x 4, then q4w, for a total of 12 doses (39w; PET-CTs at w6, w19, and w42). Planned accrual for this cohort is 25 pts. Immune responses were assayed on thawed pt peripheral blood mononuclear cells by flow cytometry and EO2463 peptide specific tetramers or by IFN-γ ELISPOT (assaying responses against 9-mer peptides from CD20, CD22, CD37, and CD268; and from peptides of EO2463) without any proceeding in vitro stimulation (ex vivo). Results As of June 2024, 15 pts had started study treatment. Median age was 62 (range 55-66) year, 7 male and 6 female, 2 pts Ann Arbor stage I/II, 5 stage III, and 8 stage IV. Ten of 15 pts were still on treatment; median treatment duration was 18.4 weeks (range 5-39 w) for all pts. Among 13 evaluable pts, best responses by PET-CT using Lugano criteria were 1 pt CR, 5 pts PR (46% objective responses (OR)), 3 pts SD, and 4 pts PD. Of those with PD per Lugano, 2 had isolated increases in FDG-uptake without increase in lesion size/number at w6 and both remain on treatment (per protocol based on LYRIC criteria). OR was first noted w6 in 3 pts and w19 in 3 pts; duration of response is not evaluable at this time due to short follow-up. The pt with CR had isolated increases in FDG-uptake at w6, PR at w19, and CR at w35. Anti-EO2463 immune responses were observed in 4 of 5 tested pts at the 1st testing timepoint (w5) and onwards (currently longest tested up until w31). In an exploratory analysis, the percentage of EO2463 peptide specific CD8 T cells measured by tetramers seemed linked to clinical response (OR 3 pts vs non-OR 2 pts; 2-sided T-test, p=0.02; range of percentages in pts with OR 0.85%-1.39% of all CD8 T cells in peripheral blood, range in pts with non-OR 0.17%-0.27%). Functionality and cross-reactivity of responses were shown by IFN-γ ELISPOT using 9-mer peptides corresponding to the B cell targets in 4 tested pts. Expanded antigen-specific CD8 T cells displayed a memory phenotype; effector/memory (TEM), and terminally differentiated effector memory CD8 T cells (TEMRA). The most common related AEs were grade 1 (7 pts) and grade 2 (5 pts) local administration site reactions (mainly erythema, pruritus, and induration). Other related AEs in &gt; 1 pt were grade 1 headache (2 pts) and grade 1-3 fatigue/asthenia (3 pts). Asthenia lasting 2 days was the only related grade 3 adverse event (AE). Conclusions EO2463 monotherapy is associated with a very manageable safety profile and appears to demonstrate meaningful single-agent efficacy in FL. Consistent with the preclinical hypothesis, expansion of specific CD8 memory T cells may be associated with response. Results will be expanded at the meeting. Study EONHL1-20/SIDNEY also includes cohorts, not covered in this abstract, exploring EO2463 plus rituximab for 1st line FL/MZL, and EO2463 plus lenalidomide/rituximab in relapsed FL/MZL.

Introduction: Acute kidney injury (AKI) due to cast nephropathy is a medical emergency that leads to a diagnosis of myeloma in less than 3% of cases, but up to 30% of patients develop kidney impairment during the course of their disease. Currently, studies aiming to identify parameters that correlate with kidney function recovery and response to myeloma are limited due to small sample size or single center reports. We have therefore initiated an international collaboration and collected a large number patients (pts) from 16 participating centers. Objectives: To assess the impact of pts and disease characteristics and treatment-specific factors on renal outcome and overall survival and to validate the IMWG criteria for renal response in pts with cast nephropathy and newly diagnosed MM. Patients and Methods: Three-hundred forty-three pts (median age: 65.5 range 35-93 yrs) with newly diagnosed MM and an eGFR &lt;40ml/min/1.73m2 have been selected from 704 pts that had been enrolled in the database hosted by RedCap. Eligibility criteria were a diagnosis of AKI due to cast nephropathy diagnosed either by kidney biopsy (n=119) or on clinical criteria (AKI in the setting of involved free light chain concentration of ≥500 mg/L), newly diagnosed multiple myeloma, &gt;2 cycles of therapy, time and type of therapy, best eGFR and best myeloma response available. Results: Median follow up was 36.9 months. Myeloma therapy resulted in renal CR, and PR as defined by the IMWG criteria in 131 (38.2%) and 57 (16.6%) pts, respectively, 54 (15.7%) and 82 (23.9%) pts had minor response or no response, respectively. Nineteen (5.5%) pts were not classifiable by the IMWG response criteria (pts with eGFR 15-&lt;30, with increase to eGFR to ≥30-&lt;40). An eGFR of &gt;60, ≥30-&lt;60, ≥15-&lt;30, and &lt;15ml/min was achieved by 131 (38.2%), 112 (32.7%), 67 (19.5%), and 33 (9.6%) pts respectively. Myeloma response (≥VGPR) correlated significantly with renal response (≥PRrenal) (OR 1.64, CI 1.05-2.56, p=0.03) and with OS compared to no myeloma response (median 89.7 vs. 39.7 months, HR 2.12, CI 1.55-2.89, p&lt;0.0001). A &gt;50% reduction in FLCs from baseline to treatment cycle 2 (OR 5.92, CI 2.15-19.23, p=0.001) and cycle 3 (OR 5.25, CI 2.15-19.25, p=0.006) were strongly associated with renal response Median OS was 69.6 months (CI 55.4-89.7). Forty-three pts died within the first 12 months of treatment and additional 146 during further FU. Pts with a best GFR of &gt;15ml/min had a significantly longer OS compared to those with GFR &lt;15ml/min (median: 77.9 vs 31.9 months, HR 1.85, CI 1.16-2.94, p=0.01). The comparison of survival of pts with different renal response groups and with the best eGFR showed no statistically significant difference (log rank p=0.1, long rank p=0.057, respectively). Other factors that correlated with longer OS were bortezomib-based therapy (77.9 vs. 44.0 months, HR 1.59, CI 1.05-2.38, p=0.03), M-protein isotype with κ as compared to l light chain type (84.9 vs. 51.4 months, HR 1.47, CI 1.09-2.00, p=0.013), and higher hemoglobin (HR 1.16, CI 1.06-1.26, p=0.001). In contrast, hypercalcemia which was noted in 101 (29.4%) pts (HR 1.10, CI 1.03-1.18, p=0.005), ISS stage III vs. I-II (57.8 vs. 126.2 months, HR 2.26, CI 1.22-4.17, p=0.009), and ECOG status 3+4 vs. 2 vs. 0+1 (24.4 vs. 44.6 vs. 103 months, HR 2.83, CI 2.15-3.74, p&lt;0.0001) were associated with shorter OS. Hypercalcemia, correlated with renal response (OR 1.27, CI 1.12-1.44, p=0.0002), and best eGFR ≥46.4 ml/min (median dichotomized) (OR 1.28, CI 1.14-1.46, p&lt;0.0001). 119 (34.7%) pts required initial dialysis, OS was significantly longer in those who achieved best eGFR levels of &gt;15ml/min. (77.6 vs 31.9 months, HR 0.54, CI 0.34-0.86, p=0.01); 64 (53%) pts discontinued dialysis. Conclusion: Myeloma response correlated with renal response as defined by IMWG criteria. A &gt;50% reduction in FLCs from baseline to treatment cycle ≥2 was strongly associated with renal response. OS was longer in pts with renal response, in pts receiving bortezomib-based therapy, and in pts with kappa light chain M-proteins. Hypercalcemia was frequent (29.4%), and associated with higher renal response rate and best eGFR, but shorter OS. Pts on dialysis who achieved eGFR &gt;15ml/min had better survival. Fast diagnostic work up, rapid treatment initiation and achieving significant myeloma response (≥VGPR) is essential to prevent irreversible kidney damage. Including novel immunotherapies may further improve outcome.