Citations

Purpose: Functional septorhinoplasty is an effective treatment for nasal airway obstruction. Little distinction exists between bilaterally and unilaterally obstructed patients in literature. Our study evaluates outcomes in patients with unilateral nasal airway obstruction compared to those with bilateral nasal airway obstruction as measured by nasal obstruction symptom evaluation scores following functional septorhinoplasty. Materials and Methods: A total of 227 patients underwent functional septorhinoplasty for nasal airway obstruction. Patients were grouped into unilateral (n = 64) and bilateral (n = 163) nasal obstruction cohorts based on patient report and physician assessment. Nasal obstruction symptom evaluation (NOSE) scores were obtained pre-operatively and post-operatively at least 3 months following surgery. Results: Patients with unilateral nasal obstruction had slightly less severe symptoms preoperatively than patients with bilateral obstruction. Average preoperative NOSE scores for patients with unilateral obstruction was 64 (SD = 19) and 72 (SD = 18) for patients with bilateral obstruction ( P = .004). Postoperative NOSE scores following septorhinoplasty were significantly reduced for patients with both unilateral and bilateral nasal obstruction (postoperative NOSE scores unilateral: 17, SD = 16 ; bilateral: 23, SD = 21). There was no statistical significance in outcomes between patients with unilateral or bilateral nasal obstruction groups. Conclusions: Symptoms in patients with unilateral obstruction are similar but slightly less severe than patients with bilateral obstruction. Patients with unilateral and bilateral nasal obstruction experienced a similar degree of improvement in symptom following functional septorhinoplasty.

Pancreatic cystic lesions (PCLs) represent a spectrum of non-neoplasms and neoplasms with varying malignant potential, posing significant challenges in diagnosis and management. While some PCLs are precursors to pancreatic cancer, others remain benign, necessitating accurate differentiation for optimal patient care. Conventional approaches to PCL management rely heavily on radiographic imaging, and endoscopic ultrasound (EUS) guided fine-needle aspiration (FNA), coupled with clinical and biochemical data. However, the observer-dependent nature of image interpretation and the complex morphology of PCLs can lead to diagnostic uncertainty and variability in patient management strategies. This review critically evaluates current PCL diagnosis and surveillance practices, showing features of the different lesions and highlighting the potential limitations of conventional methods. We then explore the potential of artificial intelligence (AI) to transform PCL management. AI-driven strategies, including deep learning algorithms for automated pancreas and lesion segmentation, and radiomics for analyzing heterogeneity, can improve diagnostic accuracy and risk stratification. These advanced techniques can provide more objective and reproducible assessments, aiding clinicians in decision-making regarding follow-up intervals and surgical interventions. Early results suggest that AI-driven methods can significantly improve patient outcomes by enabling earlier detection of high-risk lesions and reducing unnecessary procedures for benign cysts. Finally, this review emphasizes that AI-driven approaches could potentially reshape the landscape of PCL management, ultimately leading to improved pancreatic cancer prevention.

We present a case study of neotricuspidization of the aortic valve with neocusp suturing based on templates similar to those used in the Ozaki procedure but adapted for infants. This is an alternative for patients when valve reconstruction is impossible or risky. A good postoperative hemodynamic outcome was obtained, but it is necessary to evaluate this approach on the basis of long-term results.

Abstract Kidney disease is a common complication of monoclonal immunoglobulin (MIg)–secreting B-cell disorders and predominantly occurs in patients who do not meet the criteria for an overt hematological disease. To distinguish this situation from monoclonal gammopathy of undetermined significance, which lacks organ damage, the term monoclonal gammopathy of renal significance (MGRS) was introduced to depict the association of a small, otherwise indolent B-cell clone, with renal disease induced by the secreted MIg. The spectrum of renal disorders in MGRS is wide, encompassing both tubular and glomerular disorders, classified according to the composition of deposits and their ultrastructural pattern of organization. Renal lesions, independent of the tumor burden, are mostly governed by the molecular characteristics of the MIg variable domain and involve either direct (deposition or precipitation) or indirect (autoantibody activity, complement activation) mechanisms. The diagnosis, often suggested by careful analysis of renal and extrarenal symptoms, almost always requires histological confirmation by a kidney biopsy with light, immunofluorescence, and electron microscopy studies. Most patients do not have a known monoclonal gammopathy at presentation. Hematologic investigations should include serum and urine protein electrophoresis and immunofixation, serum-free light chain measurements, and bone marrow studies with flow cytometry and cytogenetics to determine the nature of the pathogenic clone (most commonly plasmocytic). Early diagnosis before the development of severe chronic kidney disease and rapid achievement of deep hematological response through clone-targeted chemotherapy (currently based on proteasome inhibitor and monoclonal anti-CD38 antibody–based combinations for plasma cell clones) are the main factors influencing long-term renal and patient outcomes.

Background: The BeatAML Master Trial (BAMT) began in 2016 with a goal of determining the feasibility of a precision-medicine approach in treating acute myeloid leukemia (AML) in older adults ≥ 60 years of age where outcomes are poor. At the time, standard of care (SOC) for older patients with AML was intensive 7+3 chemotherapy (cytarabine + daunorubicin) if fit and hypomethylating agents (HMA: azacitidine or decitabine) if unfit. Besides confirming the feasibility, the early results (2019) from the Master Trial suggested that patients who received therapy on one of the sub-studies had a lower early death rate and superior overall survival compared to patients receiving off-protocol SOC, which was primarily single-agent HMA at the time. Since then, the 2019 approval of venetoclax (ven) + azacitidine for older unfit AML patients has been transformative and emerged as the SOC. Using data from the BAMT from 2016-2024, we suggest that knowing the comprehensive genomic profile of AML at the time of diagnosis is still beneficial in determining therapy that would lead to the optimal outcome and that development of targeted therapies and combination regimens with ven/HMA is still needed. Methods: This is a retrospective analysis of 1096 patients who consented and enrolled on the BAMT (NCT03013998) from Nov 2016 through Jun 2024. Patients ≥ 60 years with newly diagnosed AML were included. Patients underwent therapy on a BeatAML sub-study based on their genetics (N=433) or treatment off-protocol (N=663). We divided the patients according to what therapy they received: (1) Non-Intensive (Off-Protocol, N=121), (2) Ven/HMA (Off-Protocol, N=234), (3) Non-Intensive (Sub-Study, N=407), (4) Intensive (Sub-Study, N=26), and (5) Intensive (Off-Protocol, N=155). 94 patients received no treatment and 59 were unknown. Non-intensive therapies included primarily targeted agents or non-ven combinations. We analyzed baseline characteristics and demographics, overall survival (OS), and the impact of allogenic stem cell transplant (SCT). OS, using Kaplan-Meier method, was measured from the start of therapy to all-cause death, censoring patients at last follow-up. Results: Characteristics and demographics were similar between Groups 1, 2 and 3. Group 4 and 5 were treated with intensive chemotherapy and their characteristics are reflective of younger/fit patients appropriate for the intensive regimen. Groups 4 and 5 also had the longest median OS (mOS) of 40.2 months (95% CI: 13.9-not reached (NR)) and 42.3 months (95% CI: 25.1-NR) respectively. Group 3, which included patients treated with a non-intensive, targeted therapy on a sub-study, had an mOS of 14.0 months (95% CI: 12.3-16.7), which was similar to Group 2, treated with Ven/HMA, that had an mOS of 13.2 months (95% CI: 10.9-16.3). Lastly, patients in Group 1, who were treated primarily with HMA monotherapy, did poorly in comparison, with an mOS of 6.0 months (95% CI: 3.3-10.1). Additionally, we looked at the cumulative incidence rate (CIR) of SCT. The CIR in 12 months of Group 1 was 9.8% (95% CI: 6.9-13.4), Group 2: 5.4% (95% CI: 2.2-10.7), Group 3 and 4 combined: 35.0% (95% CI: 628.1-42.1), and Group 5: 13.1% (95% CI: 6.9-13.4). In a multi-variable analysis, after adjusting for typical favorable risk factors like NPM1 mutations and core binding factor, SCT was highly significant (p<0.0001) in improving OS with a hazard ratio of 0.23 (95% CI: 0.16-0.32), and Group 3 performed similarly to Group 2 (p=0.20). Conclusions: First, our results suggest that it is clinically relevant to correctly identify whether an intensive chemotherapy, targeted-therapy, or ven/HMA regimen is best suited for older AML patients, for which a precision-medicine trial is ideal for. Secondly, in this group of patients, our results show that patients treated with a non-intensive targeted therapy (Group 3) has a similar mOS to those treated with ven/HMA (Group 2). Especially after controlling for patient characteristics, patients in Group 2 performed similar to those in Group 3 (p=0.20). Patients in Group 3 were treated on Beat AML sub-studies which included targeted therapy alone or with non-venetoclax combinations, which is a strong rationale for continued development of targeted agents to optimize toxicity and quality of life with similar survival. Lastly, this data also supports the need to improve the ven/HMA SOC by developing combination regimens with targeted agents to further improve outcomes.

Background: Systemic mastocytosis (SM) is a rare disease characterized by neoplastic mast cell (MC) infiltration of extracutaneous tissues. Nonadvanced SM (NonAdvSM) is associated with debilitating symptoms which may significantly reduce health-related quality of life (HRQoL). In up to 95% of patients (pts), SM is driven by the somatic KIT c.2447 A>T (p.D816V) missense mutation. Bezuclastinib (bezu; CGT9486) is an oral, potent, small molecule, selective type 1 tyrosine kinase inhibitor (TKI) with activity against KIT D816V. Results from Part 1 of the 3-part Summit trial demonstrated that bezu is well-tolerated and is associated with encouraging clinical activity, including both reduced MC burden and improvement in symptoms over a 12-week (wk) period vs placebo (PBO). Based on safety, PK, biomarker, and efficacy results, a dose of 100mg QD bezu (optimized formulation) was selected for Summit Part 2. Trial Design and Methods: Summit (NCT05186753) is a multi-center, Phase 2, double-blind, PBO-controlled RCT of bezu in pts with NonAdvSM who have inadequate control of symptoms despite treatment with best supportive care (BSC). A novel pt-reported outcome measure, the Mastocytosis Symptom Severity Daily Diary (MS2D2), was designed to assess disease-specific symptom severity in NonAdvSM pts. Eleven symptoms are included in the MS2D2 Total Symptom Score (TSS). Summit Part 1a randomized pts 1:1:1 to PBO, 100mg, or 200mg, original formulation while Part 1b randomized 1:1:1 to PBO, 100mg, or 150mg, optimized formulation. Pts completing Part 1 of the Summit trial were allowed to receive bezu in the open-label extension (OLE) Part 3 of the trial. Results: As Part 2 will evaluate safety and efficacy of 100 mg bezu at 24 wks, this abstract reports on pts treated with both bezu formulations at 100mg in Parts 1a or 1b, which had similar PK exposures. The presentation will focus on 24-wk outcomes in pts receiving the selected 100 mg bezu dose and participating in the OLE. In Summit Part 1, 19 pts received PBO and 18 received 100 mg bezu for 12 wks. At baseline (BL), the symptoms identified as most severe were within the skin and fatigue domains. At BL, pts were managing their symptoms of NonAdvSM with 2 (43%), 3 (24%), or ≥4 (32%) BSC medications. At the 12-wk assessment in Part 1 (datacut 18Dec2023), the safety and tolerability profile was encouraging, with the majority of TEAEs low grade and reversible without dose modification. The most common TEAEs (>10% in 100 mg bezu) included hair color changes, nausea, diarrhea, peripheral edema, GERD, taste disorder, and neutropenia. There were no reported bleeding or cognitive impairment events. Of 37 pts randomized to PBO or 100 mg QD bezu, 36 (97%) received bezu in the OLE; one pt randomized to the 100 mg original formulation dose reduced and subsequently discontinued due to TEAE of ALT increase. All 19 PBO pts (100%) crossed over to receive bezu in the OLE; of these, 9 were randomized to the 100mg QD bezu dose. Reduction in MC burden was robust among those treated with 100mg bezu - 94.4%, 100%, and 92.3% of pts had at least a 50% reduction in basal serum tryptase, KIT p.D816V variant allele frequency, and bone marrow MCs, respectively. Pts treated with 100 mg bezu had reduction in MS2D2 TSS by 49.1% vs 21.1% with PBO. On a 0-10 scale, the most severe MS2D2 symptom mean change from BL was -3.03 from a BL mean of 7.6 with bezu vs -1.04 from a BL mean of 7.7 with PBO. Individual symptoms of the MS2D2 TSS, as well as others not in the TSS including diarrhea and brain fog, improved more with bezu than with PBO; mean change from BL ranged from -1.66 to -2.69 with bezu vs. a range of -0.52 to -1.58 with PBO. LS mean change from BL in quality of life (Mastocytosis (MC)-QoL, a disease-specific measure) was -22.05 in pts treated with 100mg bezu versus -10.71 in pts treated with PBO. Objective measurements of skin lesions, including centrally adjudicated longitudinal assessments of skin photography, also significantly reduced on bezu. Conclusions: In Part 1 (12 wk assessment), treatment with 100mg bezu resulted in favorable safety and tolerability, significant and deep reductions across all markers of MC burden, and clinically meaningful reduction in all individual MS2D2 TSS symptoms and across domains. The presentation will report on durability and safety/tolerability data beyond 12 wks for those pts randomized to 100 mg in Part 1 and pts who crossed over from PBO in Part 1 to 100mg in Part 3. Summit Part 2 is actively enrolling.

Background: Overall survival rates now exceed 90% for children, adolescents, and young adults with cHL, but patients with slow early response (SER) to front-line chemotherapy are at an increased risk of relapse. The approaches used historically to treat patients with SER included dose intensification and radiotherapy (RT), which can be associated with long-term toxicity. The open-label, phase 2 KEYNOTE-667study (NCT03407144) is designed to evaluate the efficacy and safety of consolidation with pembrolizumab plus chemotherapy with or without RT followed by pembrolizumab maintenance in patients with cHL and SER to front-line chemotherapy. The study includes 2 groups: patients with low-risk cHL (stage IA, IB, or IIA without bulky disease) and patients with high-risk cHL (stage IIEB-IVB). Prior analysis of the high-risk group showed that consolidation with pembrolizumab plus cyclophosphamide, vincristine, prednisone/prednisolone, and dacarbazine (COPDAC-28) followed by pembrolizumab maintenance had manageable safety and promising activity in patients with high-risk cHL and SER to front-line vincristine, etoposide, prednisone/prednisolone, and doxorubicin (OEPA). Here, we present updated results for patients with high-risk cHL and SER to OEPA. Methods: Patients eligible for the high-risk group were aged 3-25 years and had newly diagnosed stage IIEB, IIIEA, IIIEB, IIIB, IVA, or IVB cHL; measurable disease; and a Lansky Play-Performance Scale (aged <16 years) or a Karnofsky Performance Status (aged ≥16 years) score of ≥50. All patients in the high-risk group received 2 cycles of OEPA followed by early response assessment (PET and CT/MRI). Patients with a rapid early response (ie, Deauville score [DS] 1-3) received nonstudy therapy. Patients with a SER (ie, DS 4 or 5) received consolidation therapy with pembrolizumab 2 mg/kg up to 200 mg (aged 3-17 years) or 200 mg (aged 18-25 years) IV Q3W plus COPDAC-28 for 4 cycles. Patients then underwent late-response assessment (LRA; PET and CT/MRI). Patients with PET-positive disease at LRA (ie, DS 4 or 5) received RT (28.8 Gy) to late PET-positive residua. Patients with PET-negative disease (ie, DS 1-3) received no RT. All patients received maintenance pembrolizumab for up to 17 cycles. The primary end point was objective response rate (ORR) by blinded independent central review (BICR) per Cheson 2007 IWG criteria. Secondary end points included the rate of PET negativity after consolidation and safety. Results: 84 patients with high-risk cHL and SER to front-line OEPA received consolidation with pembrolizumab plus COPDAC-28. Median time from treatment allocation to data cutoff (Feb 29, 2024) was 24.3 months (range, 5.7-48.4). As of the data cutoff, 55 patients had completed consolidation and maintenance therapy, 20 were ongoing, and 9 had discontinued treatment (due to adverse events [AE], n = 3; progressive disease, n = 2; withdrawal by patient, n = 2; complete response [CR], n = 1; physician decision, n = 1). Patients received a median of 17 doses of pembrolizumab (range, 2-17) and the median time on pembrolizumab was 11.1 months (range, 0.5-11.8). The median age of patients was 14 years (range, 4-22), 78 (93%) were aged 3-17 years, 45 (54%) were male, 44 (52%) had bulky disease, and 53 (63%) had Ann Arbor stage IV disease. Of 84 patients who received consolidation, 80 (95%) had an LRA. The ORR among these patients was 99% (95% CI, 93-100; 57 CR and 22 partial response). 56 patients (70%) with a LRA were PET negative by BICR; 55 (69%) were PET negative by investigator review and did not receive RT. Treatment-related AEs were reported in 61 patients (73%); grade 3 or 4 treatment-related AEs occurred in 16 patients (19%). Three patients (4%) discontinued treatment due to treatment-related AEs. No patients died due to treatment-related AEs. Immune-mediated AEs occurred in 10 patients (12%). Conclusion: After additional follow up, consolidation with pembrolizumab plus COPDAC-28 with or without RT followed by pembrolizumab maintenance continued to demonstrate promising activity and manageable safety in patients with high-risk cHL and SER to front-line OEPA. Among the 80 patients with an LRA, 70% were PET negative by BICR and 69% were PET negative by investigator review and were spared RT. These results continue to support pembrolizumab plus COPDAC-28 consolidation as a treatment option that may augment response in patients with high-risk CHL and SER to front-line OEPA.

Introduction Relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is very aggressive, with a historically low complete response (CR) rate (Blood. 2017; 130[16]:1800-1808). Recent research has focused on achieving complete and durable responses in this population, which translate to improvements in overall survival (OS) and progression-free survival (PFS). Results from the randomized, global, phase 3 ECHELON-3 study (NCT04404283) demonstrated a statistically significant and clinically meaningful improvement in OS, PFS, and objective response rate with brentuximab vedotin (BV) combined with lenalidomide (Len) and rituximab (R; BV+Len+R) vs placebo+Len+R in patients (pts) with R/R DLBCL after ≥2 prior systemic therapies. Here, we present subgroup analyses in pts with a best overall response (BOR) of CR (n=67). Methods Pts in the study were randomized (1:1) to receive BV (1.2 mg/kg) or placebo every 3 weeks, in combination with R (375 mg/m2) and Len (20 mg) once daily. In these subgroup analyses, eligible pts had a BOR of CR and some ended study treatment and received any subsequent anticancer therapy. BOR was assessed by investigators according to the Lugano 2014 classification. Duration of response was defined as the time from the start of the first documented CR to the first documented tumor progression per Lugano 2014 or death. Pts who initiated a subsequent nonpalliative anticancer therapy were censored at the most recent prior response assessment. Subsequent nonpalliative anticancer therapies were defined as any systemic therapy received after the end of study treatment. P values are descriptive. Results Of the 112 pts in the BV+Len+R group, 45 (40.2%) had a BOR of CR. Of the 118 pts in the placebo+Len+R group, 22 (18.6%) had a BOR of CR. The median duration of CR was 18.9 months (95% CI, 11.1 months-not estimable [NE]) with BV+Len+R vs not reached (NR) with placebo+Len+R (hazard ratio [HR], 0.527; 95% CI, 0.200-1.389; P=.1891). The median time to CR was 1.58 months (range, 1.2-7.3 months) with BV+Len+R and 1.61 months (range, 0.7-4.6 months) with placebo+Len+R. With a median follow-up of 14.3 months, the median OS in pts with a BOR of CR was 31.5 months (95% CI, 20.3 months-NE) in the BV+Len+R group vs NR in the placebo+Len+R group (HR, 1.044; 95% CI, 0.331-3.298; P=.9407). Median PFS in pts with a BOR of CR was 21.5 months (95% CI, 12.6 months-NE) in the BV+Len+R group vs NR (95% CI, 5.4 months-NE) in the placebo+Len+R group (HR, 0.6333; 95% CI, 0.256-1.567; P=.3198). Results of NR in the placebo+Len+R group are likely attributable to limited follow-up and small sample size. Additional data on baseline characteristics of pts who had CR will be presented. Of the 45 pts with CR in the BV+Len+R group, 42 (93.3%) received no subsequent anticancer therapy. Of the 22 pts with CR in the placebo+Len+R group, 17 (77.3%) received no subsequent anticancer therapy. Conclusions BV doubled the CR rate in pts with R/R DLBCL compared with placebo, and outcomes in pts with CR were durable, with only 6.7% of pts treated with BV+Len+R receiving subsequent systemic anticancer therapy, compared with 22.7% of pts treated with placebo+Len+R receiving subsequent therapy. Overall, BV+Len+R demonstrated a survival benefit in the ECHELON-3 study and is a promising option to achieve complete and durable responses in third- or later-line therapy for pts with R/R DLBCL.

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 <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, >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-<30, with increase to eGFR to ≥30-<40). An eGFR of >60, ≥30-<60, ≥15-<30, and <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<0.0001). A >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 >15ml/min had a significantly longer OS compared to those with GFR <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<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<0.0001). 119 (34.7%) pts required initial dialysis, OS was significantly longer in those who achieved best eGFR levels of >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 >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 >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.

Background: Cure rates for children, adolescents, and young adults with cHL are high, but patients with a slow early response (SER) to front-line chemotherapy are at an increased risk of relapse compared with patients who have a rapid early response (RER). To avoid long-term toxicity while optimizing outcomes, treatment for pediatric cHL is now shifting to a response-adapted approach. KEYNOTE-667 (NCT03407144) is an open-label phase 2 study designed to evaluate the efficacy and safety of pembrolizumab plus chemotherapy consolidation with or without radiotherapy (RT) followed by pembrolizumab maintenance in patients with cHL and SER to front-line chemotherapy. The study includes 2 groups of patients: those with low-risk cHL (stage IA, IB, and IIA without bulky disease) and those with high-risk cHL (stage IIEB-IVB cHL). Prior analysis of the low-risk group showed that consolidation with pembrolizumab plus doxorubicin, vinblastine, and dacarbazine (AVD) and RT followed by maintenance pembrolizumab had manageable safety and promising antitumor activity in patients with low-risk cHL and SER to front-line doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). We present updated results for patients with low-risk cHL and SER to ABVD. Methods: Patients eligible for the low-risk group were aged 3-25 years and had newly diagnosed stage IA, IB, or IIA cHL without bulky disease, measurable disease, and a Lansky Play-Performance Scale score of ≥50 (aged <16 years) or a Karnofsky Performance Status score of ≥50 (aged ≥16 years). All patients in the low-risk group received 2 cycles of ABVD followed by early response assessment (PET and CT/MRI). Patients with a RER (ie, Deauville score [DS] 1-3) received nonstudy therapy. Patients with SER (ie, DS 4 or 5) received consolidation with pembrolizumab 2 mg/kg up to 200 mg (aged 3-17 years) or 200 mg (aged 18-25 years) IV Q3W plus 2 cycles of AVD. Patients then underwent late response assessment (LRA; PET and MRI/CT). All patients with SER received involved-site RT: 21.6 Gy for complete PET response (ie, DS 1-3) or 30.6-36 Gy for partial PET response (ie, DS 4 or 5). All patients received maintenance pembrolizumab for up to 17 cycles. The primary end point was objective response rate (ORR) by blinded independent central review (BICR) per Cheson 2007 IWG criteria. Secondary end points included PET negativity after consolidation and safety. Results: 78 patients with low-risk cHL received front-line ABVD. As of the data cutoff date (February 29, 2024), 10 of 78 patients had SER to ABVD and received consolidation with pembrolizumab plus AVD; 4 had completed consolidation and maintenance, 1 was continuing to receive treatment, and 5 had discontinued because of complete response (CR). Median time from allocation to data cutoff was 19.9 months (range, 5.6-44.8). Patients had received a median of 11.5 doses of pembrolizumab (range, 5-17) and the median time on pembro was 7.4 months (range, 3.5-11.3). The median age of patients was 16 years (range, 7-20), 6 (60%) were male, and 8 (80%) had Ann Arbor stage II disease. Of 10 patients who received consolidation, all (100%) had an LRA. The ORR was 100% (95% CI, 69-100; 9 CR and 1 partial response). Six patients (60%) were PET negative by BICR. Seven patients (70%) were PET negative by investigator review, all of whom received a reduced dose of RT. During consolidation, treatment-related adverse events (AEs) were reported in 8 patients (80%); grade 3 or 4 treatment-related AEs occurred in 4 patients (40%). No patients discontinued or died due to treatment-related AEs. Seven patients (67%) had pembrolizumab-related AEs, 3 of whom (30%) had a grade 3 event (vomiting, lymphocyte count decreased, white blood cell count decreased). Immune-mediated AEs occurred in 3 patients (30%; all grade 1 or 2 hypothyroidism). Conclusion: After additional follow-up, consolidation withpembrolizumab plus AVD and RT followed by pembrolizumab maintenance continued to demonstrate promising activity and manageable safety in patients with low-risk cHL and SER to ABVD. Of patients with a LRA, 60% were PET negative by BICR; 70% of patients were PET negative by investigator review and received a reduced dose of RT. These results support further evaluation of pembrolizumab plus AVD consolidation as a treatment option for patients with low-risk CHL and SER to front-line ABVD.