5y Overall Survival Research Articles

Evaluation of MRD-status in post-induction period in pediatric patients with acute lymphoblastic leukemia.

The need to study the significance of minimal residual disease (MRD) at the induction therapy in patients with acute lymphoblastic leukemia (ALL) is beyond doubt. This has been confirmed by many years of work by many research groups. The role of MRD in the late stages of treatment and the impact of these values on patients survival requires research and discussion. To evaluate the influence of MRD-status in post-induction period on survival in patients with acute lymphoblastic leukemia. From 2010 to 2022, 135 patients with primary B-ALL enrolled in ALL-IC BFM 2009 protocol. Median age was 5.4 year (range 1-17). Male was 62 (49,5%) and female 73 (54,1%). The diagnosis was based on WHO 2016 criteria. Stratification on prognostic risk groups was carried out according to protocol criteria. Prednisone response evaluated at day 8 of treatment. The 15th, 33th, and 78th (as post-induction) day response was assessed by bone marrow cytology and level of MRD by flow cytometry. 5y-overall survival (OS) for patients with MRD-negative status on day 15 was 94,4±5,4% and 87,0±3,4% for MRD-positive (p=0,5). On day 33 patients with MRD-negative status achieved 5y-OS in 86,7±5,8% and 89,6±3,5% for MRD-positive (p=0,6).5y-OS for patients with MRD-negative status on day 78 was 90.8±4.0%, MRD-positive - 90,4+6.5%. DFS for MRD-negative status was 88.5±4.5%, for MRD-positive - 66.3±11.8% (p=0,1). EFS for MRD-negative patients was 87.2±4,6% and for MRD-positive 66.3±11.8% (p=0,09). We have found a tendency between MRD status on day 78 and the frequency of relapses in patients. At the moment, there are no reliable data on the effect of post-induction MRD status on survival. The assessment of MRD in the post-induction period has prognostic prospects and requires further study.

Thrombin Generation and D-Dimer for Prediction of Disease Progression and Mortality in Patients with Metastatic Gastrointestinal Cancer.

Simple SummaryAssessing the prognosis of a patient with cancer is of the greatest clinical interest and can provide useful information on the type and intensity of the anticancer treatment to be administered. The emerging predictive role of coagulation biomarkers in cancer prognosis needs to be confirmed by prospective cohort studies. In this study, we evaluated whether prechemotherapy levels of thrombotic biomarkers may predict for early disease progression and overall survival in a large prospective cohort of patients with metastatic gastrointestinal cancer specifically enrolled for the intended aims. We found that pretreatment thrombin generation and D-dimer appear to be promising candidate biomarkers for both outcomes.Background: the tight and reciprocal interaction between cancer and hemostasis has stimulated investigations on the possible role of hemostatic biomarkers in predicting specific cancer outcomes, such as disease progression (DP) and overall survival (OS). In a prospective cohort of newly diagnosed metastatic gastrointestinal (GI) cancer patients from the HYPERCAN study, we aimed to assess whether the hemostatic biomarker levels measured before starting any anticancer therapy may specifically predict for 6-months DP (6m-DP) and for 1-year OS (1y OS). Methods: plasma samples were collected and tested for thrombin generation (TG) as global hemostatic assay, and for D-dimer, fibrinogen, and prothrombin fragment 1 + 2 as hypercoagulation biomarkers. DP and mortality were monitored during follow-up. Results: A prospective cohort of 462 colorectal and 164 gastric cancer patients was available for analysis. After 6 months, DP occurred in 148 patients, providing a cumulative incidence of 24.8% (21.4–28.4). D-dimer and TG endogenous thrombin potential (ETP) were identified as independent risk factors for 6m-DP by multivariate Fine–Gray proportional hazard regression model corrected for age, cancer site, and >1 metastatic site. After 1 year, we observed an OS of 75.7% (71.9–79.0). Multivariate Cox regression analysis corrected for age, site of cancer, and performance status identified D-dimer and ETP as independent risk factors for 1y OS. Patients with one or both hemostatic parameters above the dichotomizing threshold were at higher risk for both 6m-DP and 1-year mortality. Conclusion.: in newly diagnosed metastatic GI cancer patients, pretreatment ETP and D-dimer appear promising candidate biomarkers for predicting 6m-DP and 1y OS. In this setting, for the first time, the role of TG as a prognostic biomarker emerges in a large prospective cohort.

Long-term survival of early stage I epithelial ovarian cancer: A multicenter retrospective observational study (321)

<b>Objectives:</b> Therapy for early-stage epithelial ovarian cancer (EOC) involves complete surgical staging with or without adjuvant chemotherapy. The current international multi-center study aimed to investigate the long-term survival of different histological subtypes for stage I EOC. <b>Methods:</b> A multi-center cohort study was performed among all patients with FIGO stage I (IA-IC3) EOC treated at four European referral centers between 1985 and 2021. Overall survival (OS) and progression-free (PFS) survival were compared between the different stage I groups using Kaplan-Meier survival curves. <b>Results:</b> A total of 1115 patients met the inclusion criteria. Of them, 48.4% (<i>n</i>=540) were in stage IA, 6.6% (<i>n</i>=73) stage IB, and 45% (<i>n</i>=502) stage IC: stage IC1 54% (<i>n</i>=271), stage IC2 31.5% (<i>n</i>=158), and stage IC3 14.5% (<i>n</i>=73). The predominant histologic subtypes included highgrade serous (25.4%), low-grade endometrioid (24.8%), and clear cell (19%). Complete surgical staging, including lymphadenectomy, was performed in 62.1%, and 60% received adjuvant platinum-based chemotherapy. The median follow-up was 48 months. The median five-year (5y) OS and PFS rates were 94% and 86%, respectively, with no difference between stage IA and IB. However, a significantly better OS and PFS were observed for stage IA as compared to stage IC (p=0.007 and p<0.001, respectively). Considering histologic subtypes, a significant better PFS was documented for low-grade mucinous and low-grade endometrioid subgroup (HR: 0.22; 95% CI: 0.09-0.45, p=0.001; HR: 0.49; 95% CI: 0.29-0.83, p=0.007, respectively), as well a better OS for the latter (HR: 0.43; 95% CI: 0.22-0.86, p=0.017). In stage IA-B, the different histology subtypes showed a comparable prognosis (5y: OS: 96% and PFS: 92%), with the exception of a worsened OS for high-grade mucinous cases (HR: 5.90; 95% CI: 1.55-22.4, p=0.009). Among stage IC, the histologic subgroups showed comparable OS (5y 92%), but significantly better PFS for low-grade mucinous and low-grade endometrioid subtypes (HR: 0.21; 95% CI: 0.05-0.86, p=0.031; HR: 0.44; 95% CI: 0.23-0.84, p=0.013, respectively). In the subgroup of high-grade serous ovarian cancer patients in stage IC disease, the chemotherapy with carboplatin/paclitaxel seems to be superior compared to single-agent platinum (5y OS: 100% vs 83%; p=0.009). In multivariate analysis, partial staging procedure (compared to complete) was found as risk factor for worsen PFS (HR: 1.73; 95% CI: 1.13-2.66, p=0.012), while low-grade endometrioid histology (compared to high-grade serous) showed better outcome regarding OS (HR: 0.46; 95% CI: 0.22-0.95, p=0.036) and PFS (HR: 0.42; 95% CI: 0.25-0.73, p=0.002). <b>Conclusions:</b> Overall, stage I ovarian cancer patients treated in referral centers exhibited an excellent prognosis regardless of the histologic type. Histologic subtype and quality of surgical treatment affect the prognosis. Our data suggest platinum-based combination chemotherapy for the subgroup of FIGO stage IC high-grade serous ovarian cancer.

Outcomes of poor peripheral blood stem cell mobilizers with multiple myeloma at the first mobilization: A multicenter retrospective study in Japan.

Autologous stem cell transplantation (ASCT) remains an important therapeutic strategy for multiple myeloma; however, a proportion of patients fail to mobilize a sufficient number of peripheral blood stem cells (PBSCs) to proceed to ASCT. In the present study, we aimed to clarify the characteristics and outcomes of poor mobilizers. Clinical data on poorly mobilized patients who underwent PBSC harvest for almost 10 years were retrospectively collected from 44 institutions in the Japanese Society of Myeloma (JSM). Poor mobilizers were defined as patients with less than 2 × 106/kg of CD34+ cells harvested at the first mobilization. The proportion of poor mobilization was 15.1%. A sufficient dataset including overall survival (OS) was evaluable in 258 poor mobilizers. Overall, 92 out of 258 (35.7%) poor mobilizers did not subsequently undergo ASCT, mainly due to an insufficient number of PBSCs. Median OS from apheresis was longer for poor mobilizers who underwent ASCT than for those who did not (86.0 vs. 61.9 mon., p = 0.02). OS from the diagnosis of poor mobilizers who underwent ASCT in our cohort was similar to those who underwent ASCT in the JSM database (3y OS rate, 86.8% vs. 85.9%). In this cohort, one‐third of poor mobilizers who did not undergo ASCT had relatively poor survival. In contrast, the OS improved in poor mobilizers who underwent ASCT. However, the OS of extremely poor mobilizers was short irrespective of ASCT.

Role of Surgery in the Management of Liver Metastases From Gastrointestinal Stromal Tumors.

BackgroundThe clinical benefit of hepatectomy in patients with liver metastases from gastrointestinal stromal tumors (GIST) has not been well defined in this era of tyrosine kinase inhibitor (TKI). Our study aims to demonstrate the survival advantage of adding hepatectomy in patients with GIST liver metastases.MethodsInformation on patients with metastatic GIST treated or consulted between January 2006 and December 2018 was retrieved. Patients without extrahepatic metastases were included and classified into the surgical (S group) and non-surgical (NS group). Clinicopathological features were compared and their association with survival was assessed.ResultsA total of 119 patients were included in this retrospective analysis, 62 in the S group and 59 in the NS group. Comparison of clinicopathological features showed that a markedly higher proportion of patients in the S group had ≤3 hepatic lesions (79.0% vs. 29.8%, p<0.001). After a median follow-up duration of 56 months, patients in the S group had significantly better progression-free survival (PFS) and marginally improved overall survival (OS) than those in the NS group (3y PFS:86.2% vs. 64.6%, p=0.002; 5y OS: 91.5% vs. 78.3%, p=0.083). After propensity score matching, multivariate analysis identified hepatectomy as the only significant prognostic factor for PFS while age, hepatectomy and max tumor diameter were significant predictor for OS.ConclusionsAddition of hepatectomy provided longer disease control in patients with metastatic GIST confined to the liver. Upfront hepatectomy followed by imatinib therapy is worthwhile trying in patients with single and easily removable lesions.

S112: TISAGENLECLEUCEL IN PEDIATRIC AND YOUNG ADULT PATIENTS (PTS) WITH RELAPSED/REFRACTORY (R/R) B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (B-ALL): FINAL ANALYSES FROM THE ELIANA STUDY

Background: Pediatric and young adult pts with R/R B-ALL experience a treatment journey characterized by diminishing likelihood of cure and increasing morbidity. Tisagenlecleucel is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for use in pediatric and young adults with B-ALL and adults with B-cell lymphomas. Tisagenlecleucel provided high rates of remission (>80%) in children and young adults with R/R B-ALL in ELIANA, with 62% of responders remaining relapse-free at 24 mo (Grupp et al, Blood, 2018). Aims: Here, we report the final efficacy and safety analyses in pts followed up to 5.9 years post-tisagenlecleucel infusion. Methods: ELIANA (NCT02435849) was a pivotal, Phase II, open-label, multicenter, global study of tisagenlecleucel in pediatric and young adult pts with R/R B-ALL. Pts received a single infusion of tisagenlecleucel at 0.2-5.0×106 CAR+ viable T cells/kg body weight for pts ≤50 kg and 0.1-2.5×108 CAR+ viable T cells for pts >50 kg. Endpoints included overall remission rate (ORR) within 3 mo, relapse-free survival (RFS), duration of remission (DOR), overall survival (OS), persistence of B-cell aplasia, and short- and long-term safety events. Results:Results: As of September 24, 2021, 97 pts were enrolled and 79 pts (81%) received tisagenlecleucel. Median time from infusion to data cutoff was 5.5 y; 64 pts had ≥5 y of follow-up. At study entry, the median age was 11 y (range, 3-24). Pts were heavily pretreated with a median of 3 prior lines of therapy (range, 1-8) and 61% had a history of prior stem cell transplant (SCT). ORR (complete remission [CR] or CR with incomplete hematologic recovery within 3 mo after infusion) was 82% (95% CI, 72-90). Among pts in remission (CR/CRi), the 5y RFS rate was 49% (95% CI, 34-62), and the median RFS was not reached (Figure, 46.8 mo when censoring for SCT; n=15). The median time to B-cell recovery was 38.6 mo (95% CI, 23-not reached) and the probability of B-cell aplasia at 6 mo and 12 mo was 83% (95% CI, 71-91) and 71% (95% CI, 57-82), respectively. Pts with B-cell recovery (<6 mo, n=10; 6-12 mo, n=4; >12 mo, n=7) experienced a 2y cumulative incidence of relapse of 25.2% (with SCT treated as a competing risk). Among all pts, the 5y EFS and OS rates were 42% (95%CI, 29-54) and 55% (95% CI, 43-66), respectively. There were no significant differences in any efficacy endpoint between pediatric (<18 y; n=65) and young adult (≥18 y; n=14) pts. No new or unexpected AEs were reported during long-term follow-up. Among pts in remission, the most commonly reported grade ≥3 AEs occurring >1 y post-infusion were infection (20%) and cytopenias (6%). Ten (14%) pts in remission experienced long-term cytopenias persisting for >1 y; however, none of these pts experienced cytopenias persisting for >5 y (median 2 y; range, 1.1-5y). Eighty-two percent of pts received IVIG any time post-infusion. Image:Summary/Conclusion: This >5 y follow-up study demonstrates continued durable efficacy of tisagenlecleucel without late adverse effects in heavily pretreated pediatric and young adult pts with R/R B-ALL. Tisagenlecleucel continues to be a potentially curative treatment option for pediatric and young adult patients with R/R B-ALL.

IMMU-03. Synergy between TMZ and individualized multimodal immunotherapy to improve Overall Survival of IDH1 wild-type MGMT promoter-unmethylated GBM patients

Abstract The prognosis of IDH1 wild-type MGMT promoter-unmethylated GBM patients remains poor. Addition of Temozolomide (TMZ) to first-line local treatment shifted the median overall survival (OS) from 11.8 to 12.6 months. We retrospectively analysed the value of individualized multimodal immunotherapy (IMI) to improve OS in these patients. All adults meeting the criteria and treated 06/2015-06/2021 were selected. Thirty-two patients (12f, 20m) had a median age of 47y (range 18-69) and a KPI of 70 (50-100). Extent of resection was complete (11), &amp;lt;complete (12) or not documented (9). Seven patients were treated with surgery/radio(chemo)therapy and subsequent IMI (Group-1); 25 patients were treated with radiochemotherapy followed by maintenance TMZ plus IMI during and after TMZ (Group-2). Age, KPI and extent of resection were not different amongst both groups. The median OS of group-1 patients was 11m (2y OS: 0%). Surprisingly the median OS of group-2 patients was 22m with 2y OS of 36% (CI95%: 16-57), which was significantly (Log-rank: p = 0.0001) different from group-1. The data suggest that addition of IMI after local therapy on its own has no relevant effect on OS in these GBM patients, similar to maintenance TMZ. However, the combination of both TMZ + IMI significantly improved OS. This finding might also have implications in the search for novel combined treatment approaches for children with malignant glioma.

LINC-24. Survival and genetic evaluation of patients diagnosed with choroid plexus tumor treated at a Brazilian institution

INTRODUCTION: Choroid plexus tumors (CPT) are rare intraventricular neoplasms of epithelial origin. They usually occur in the 2nd year of life, corresponding to 0.4-0.6% of intracranial tumors in this age group. They are classified, according to WHO 2021: choroid plexus carcinoma (CPC), atypical choroid plexus papilloma (ACPP) and choroid plexus papilloma (CPP). Li-Fraumeni syndrome (LFS) is present in 50% of patients with CPC. In Brazil, the TP53p.R337H mutation affects 0.3% of the population in the South/Southeast. OBJECTIVE: Evaluate the genetic assessment and overall-survival (OS) of patients with CPT treated at IOP/GRAACC/UNIFESP. PATIENTS/METHODS: Between 1995-2021, 48 patients were diagnosed with CPT in our institution, 27 CPC, 18 CPP and 3 ACPP. From 2012-2021 patients were referred for genetic evaluation, 16 of which had CPC (2 had previously CPP). Family history for neoplasms was present in 87.5%, 37.5% compatible with Li-Fraumeni Syndrome (LFS) of which 50% with positive mutations. The molecular investigation of TP53 gene in patients with CPC was performed and positive in 62,5%:R337H(6 patients), R110C*, R158H*, H179R*, R196* (*1 patient each). For those with R337H, p53 protein immunohistochemistry resulted in 90-100% positivity. Treatment strategies consisted of surgery with gross total resection being achieve in all ACPP, 94,4% CPP and 55,5% CPC. Chemotherapy was performed in only 1 case of ACPP and all CPC with a variety of schemas, including high dose of chemotherapy and autologous bone marrow transplant for slow responders or recurrent disease. The three- and five-years OS for CPC was 72.5% and 61.7%, respectively. For CPP and ACPP 5y OS was 100%. CONCLUSION: The present study is in agreement with the literature showing an excellent survival for CPP and ACPP but an inferior outcome for patients with CPC and TP53 mutation despite being assisted by a well-prepared multidisciplinary team with an adequate treatment.

Clinicopathological features and management of patients with primary CNS lymphoma: Peruvian experience in two cancer centers.

e19541 Background: Primary central nervous system lymphoma (PCNSL) is an aggressive and rare extranodal non-Hodgkin lymphoma with a dismal prognosis in most patients. Outcomes in Latin population is unknown. Methods: We present a retrospective cohort of fifty-five and six newly diagnosed Peruvian patients treated at the Instituto Nacional de Enfermedades Neoplasicas from 2000-2020 and at Oncosalud from 2014-2020, respectively. Inclusion criteria were (1) histologic diagnosis of diffuse large B-cell lymphoma by two pathologists; (2) disease localized exclusively in the brain, cranial nerves, meninges, or eyes; and (3) no evidence of human immunodeficiency virus infection. Results: Median age at diagnosis was 52 years old [range 21-76]. Sixty-one percent were men. Eastern Cooperative Oncology Group performance status was ≥2 in 68% of patients. Clinical presentation was characterized by intracranial hypertension symptoms (67%), focal deficit (64%), visual disturbance (18%), and seizures (9%). elevated LDH was present in 26/46 (57%) patients, multiple lesions in 19/56 (34%) patients, and involvement of deep structures 21/62 (34%) patients. Seven patients were treated by surgery only (3, subtotal and 4, total resection), three patients received radiotherapy only, and six patients did not receive any treatment. Forty-two patients received the following chemotherapy protocols: DeAngelis (26%), high-dose methotrexate (HD-MTX) (17%), HD-MTX + high-dose ARAC (HD-ARAC) (36%) and HD- MTX + HD-ARAC + Rituximab (9%), HD-MTX + Rituximab + Temozolomide (TMZ) as induction and consolidation with etoposide (VP16) + HD-ARAC (12%), the latter was used in the private center. Clinical outcomes are described in Table. The median follow-up time was 9m (0.03-248). The median overall survival (OS) was 9.9m, 5y OS was 41.7% (95% CI, 29.2-53.9). The median OS were 6.6m and 67.3m for the public and the private institution, respectively (p=0.02). 5y OS was 34% and 100% in the public and the private center, respectively. Conclusions: Peruvian patients are 15 years younger than those reported in the literature. OS in our cohort is dismal, being poorer in those patients treated at the public center reflecting treatment disparities between the public and private health system. All patients who received HD-MTX+HD-ARAC+TMZ as induction and VP16 +HD-ARAC as consolidation achieved complete response and the median OS was not reached although this can be explained due to a short follow-up time compared to those who received DeAngelis regimen. A longer follow-up is needed to demonstrate if polychemotherapy without radiotherapy is the best treatment in this group of patients.[Table: see text]

Validation of FLIPI1, FLIPI2, PRIMA and POD24 in Patients with Extranodal Follicular Lymphoma: A Cohort from Two Cancer Centers in Peru

BackgroundFollicular lymphoma (FL) is the second most common non-Hodgkin lymphoma subtype, being nodal involvement its main characteristic. However, data about Extranodal (EN) involvement is not reported in Latin American patients. Our aim was to evaluate the clinical features, treatment patterns outcomes of Peruvian patients with ENFL from two cancer centers and validate FLIPI1, FLIPI2, PRIMA and POD-24 prognostic index in our cohort.Methods:This is a retrospective study, including all patients with a pathological diagnosis of FL grade 1 to 3A treated at the National Institute of Neoplastic Diseases and Oncosalud, both in Lima, Peru from 2010 to 2019. All cases were reviewed by specialized pathologists. Baseline clinical and pathological data were collected. Responses were assessed based on the Lugano criteria. Overall survival (OS) was estimated using the Kaplan-Meier method. Differences were compared with the log-rank test.ResultsA total of 86 patients were evaluated. The median age was 61 years (30-91), 43% were male, 20% had bulky disease (≥6 cm in diameter), 51% had stage III/IV disease, 31% had hemoglobin <12 g/dl, 11% had serum albumin <3 g/dl, 25% had elevated serum LDH, 31% had B2-microglobulin ≥3,5 mg/l, 27% had bone marrow involvement and 19% had lymph node sites >4. The most frequent EN sites were gastrointestinal, bone marrow, cutaneous and breast with 22%, 21% and 9%, and 6%% respectively. Low, intermediate and high-risk FLIPI1 was seen in 56%, 23% and 21% of patients, respectively. Low, intermediate and high-risk FLIPI2 was seen in 28%, 58% and 14% of patients, respectively. Low, intermediate, and high PRIMA was seen in 57%, 10% and 33%, respectively. 55 patients (64%) received any treatment, 47% received CHOP ± rituximab (R), 16% CVP ± R, 22% radiotherapy alone, 9% CHOP, 15% other treatments. Response data were available in 44 patients with complete response in 45%, partial response in 43% and no response in 12%, for an overall response rate of 88%. From patients who received CHOP/CVP ± R, 13% patients had disease progression within 24 months of first treatment initiation (POD24). For the entire cohort (N=88) the median follow-up time was 2.1 years (interquartile range [IQR] 0.08-11.3), median overall survival was 8.25 years (IQR 4.4-not reached [NR]). 5y OS was71.7% (95% CI 55.3-82.9), figure 1. For the FLIPI group 5y OS for low, intermediate and high FLIPI were 86.9% (95% CI 64.7-95.6), 60.1% (95% CI 24.4-83.2) and 75.7% (95% CI 30.4-93.7), respectively (p=0.07; Figure 2). For the FLIPI2 group (N=58) 5y OS for low, intermediate and high FLIPI2 were 79.5% (95% CI 39.3-94.5), 77% (95% CI 55.3-89.2) and 86% (95% CI 33.4-97.8), respectively (p=0.86). For the PRIMA group (N=38) 5y OS for low, intermediate and high PRIMA was 86% (95%55.6-96.6), 100% (95% CI 100), and 80% (95% CI 42-95), respectively (p=0.80). Patients who had and did not have POD24 had median OS of NR (IQR 0.6-NR) and NR (IQR 2.69-NR), respectively. 5y OS for patients who had and did not have POD24 was 71.2 % (95% CI 48-85) and 75% (12.7-96), respectively (p<0.87).Conclusion:Peruvian patients with ENFL showed a higher rate of female patients. Gastrointestinal involvement was the most common primary site. The OS rates is similar to our nodal involvement cohort. Chemoimmunotherapy is the standard approach to FL patients, which is associated with high rates of overall response. In our study FLIPI, FLIPI2, PRIMA and POD24 were not predictors for OS, but larger cohorts and longer follow-up are needed to find more accurate predictors of survival in these patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

ATG and Post-Transplant Cyclophosphamide Predisposes to Inferior Outcome When Using Cryopreserved Stem Cell Grafts

BackgroundDuring 2020, the novel COVID-19 pandemic lead to cryopreservation of allogeneic hematopoietic stem cell (HSCT) grafts based on NMDP and EBMT recommendations, to secure grafts before start of conditioning chemotherapy. We examined the impact of this change in practice on patient outcomes.MethodsWe retrospectively analyzed the outcomes of 483 patients who received HSCT between Aug 2017 and Aug 2020, at Princess Margaret Cancer Centre, Canada, comparing the outcomes between those who received cryopreserved (CRYO, n=135) or fresh peripheral blood stem cell grafts (FRESH, n=348). Median follow-up: 12.3 months.Probability of overall survival (OS) was calculated using the Kaplan-Meier product-limit method and heterogeneity of time-to-event distribution functions were compared by the log-rank test. Cumulative incidences of aGvHD and cGvHD, relapse, and non-relapse mortality (NRM) were estimated using the cumulative incidence method considering competing risk, and groups were compared using Gray's test. Death was considered as a competing event for relapse, aGvHD and cGvHD, and relapse was considered a competing event for NRM, aGvHD and cGvHD.ResultsMedian age was 58y; 54.5% were males. Acute myeloid leukemia was commonest HSCT indication (n=248, 49.1%). Donors: MUD 10/10 n=233; MUD 9/10 (MMUD) n=48, matched related donor (MRD) n=112, Haploidentical n=88. Transplant conditioning: 79 (23%) and 23 (17%) patients received myeloablative conditioning (MAC) in the FRESH and the CRYO groups, respectively (p ns). In the FRESH group, 253 (73%) patients and 114 (84%) patients in the CRYO group received ATG followed by posttransplant cyclophosphamide (PTCy) and Cylosporine GvHD prophylaxis.OS at the 2y timepoint, FRESH group (n=348), was 67.0% (61.1-72.3%), compared to 48.7% (38.1-58.4%) for patients in the CRYO group (n=135), p=0.002, Figure 1a. This was mainly due to MRD cohort outcomes: 2y OS in MRD FRESH group (n=65), was 85.2% (73.3-92.0%), compared to 45.1% (29.9-59.1%) in MRD CRYO group (n=47), p<0.001, Figure 2a. Multivariate analysis (MVA) for OS, significant factors were increasing patient age, DRI high/v.-high, HCT-CI ≥ 3, Donors: Haplo and MMUD, cryopreservation, Table 1.NRM at 1y for FRESH (n=348) 17% (13.2-21.2) vs CRYO (n=135) 22.1 % (14.8-30.4), p ns . However, in the MRD cohort, NRM at 1y for FRESH group (n=65), was 1.5% (0.1-7.4%), compared to 15.4% (6.6-27.4%) for CRYO group (n=47), p=0.003, Figure 2b . On MVA, NRM adverse significant factors were patient age, DRI high/v.-high, Donors: Haplo and MMUD, Table 1.Cumulative incidence (CI) of relapse at 2y for FRESH 22.4% (17.5-27.7) vs CRYO 27.0 % (18.8-35.9) p=0.07 .The CI of moderate-severe cGvHD at 1y for FRESH group (n=315) was 21.5% and 10.8% in the CRYO group, p=0.027, Figure 1c . Patients with FRESH 10/10 MUDs (n=180), had CI of moderate-severe cGvHD at 1y of 20.6%, compared to CRYO 10/10 MUDs (n=35), 6.0% p ns for MUDs; FRESH MRD (n=64) CI was 30.1%; and CRYO MRD (n=43) 10.3%, p=0.008 for MRD, Figure 1d. On MVA, significant adverse factors for chronic GvHD were increasing donor age, male recipient/female donor, whilst graft CRYO was protective, Table 1.GvHD-and Relapse free Survival (GRFS) at 2y for FRESH 54.0% (47.9-59.6) vs CRYO 43.4% (33.4-53.0) p<0.05, Figure 1b. However, in the MRD cohort, GRFS at 2y in FRESH group (n=65), was 74.2% (61.3-83.4%), compared to 40.7% (26.3-54.6%) for CRYO group (n=47), p=0.001; other donor types no difference, Figure 1c. On MVA, significant factors correlated with worse GRFS were: DRI high and very-high, cryopreservation, Donors: Haplo and MMUD, Table 1.Compared to FRESH group, CRYO group experienced reduced cGvHD, delay in neutrophil engraftment, higher graft failure and increased CMV reactivation, with no difference in relapse incidence or acute GvHD.ConclusionCryopreservation was associated with inferior outcomes post-HSCT particularly in the MRD cohort, possibly due to combination ATG and post-transplant cyclophosphamide impacting differential tolerance to cryopreservation on components of the stem cell graft; further studies are warranted to elucidate mechanisms for this observation. [Display omitted] DisclosuresLaw: Novartis: Consultancy; Actinium Pharmaceuticals: Research Funding. Lipton: Bristol Myers Squibb, Ariad, Pfizer, Novartis: Consultancy, Research Funding. Kim: Bristol-Meier Squibb: Research Funding; Paladin: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Mattsson: MattssonAB medical: Current Employment, Current holder of individual stocks in a privately-held company.

Early Integration of High Dose Methotrexate to Frontline DLBCL Therapy Does Not Impact CNS Relapse Compared to End of Treatment Delivery: A Multicentre International Analysis of 1384 Patients

Early Integration of High Dose Methotrexate to Frontline DLBCL Therapy Does Not Impact CNS Relapse Compared to End of Treatment Delivery: A Multicentre International Analysis of 1384 Patients

Dose Reduced Chemotherapy in Sequence with Blinatumomab for Newly Diagnosed Older Patients with B-Precursor Adult Lymphoblastic Leukemia (ALL): Results of the Ongoing GMALL Bold Trial

Dose Reduced Chemotherapy in Sequence with Blinatumomab for Newly Diagnosed Older Patients with B-Precursor Adult Lymphoblastic Leukemia (ALL): Results of the Ongoing GMALL Bold Trial

Clinical Characteristics and Survival of Non-Nasal Natural Killer/T-Cell Lymphoma from 2 Cancer Centers from Peru

BackgroundNatural killer/T-cell lymphoma (NKTCL) is an aggressive lymphoma with poor prognosis mainly seen in Asian and South American countries, most patients have nasal involvement. Non-nasal NKTCL have a dismal prognosis. However, data about this very specific population is mostly known in Asians but little known in Latin American (LATAM) population. Our aim is to describe the clinical characteristics and survival of newly diagnosed NKTCL patients in PeruMethods: This is a retrospective study, including all patients with a pathological diagnosis of NKTCL patients >13 years at the Instituto Nacional de Enfermedades Neoplasicas (INEN) and Oncosalud between 2002 and 2019. The estimate of the survival curves was performed by the Kaplan-Meier method, and the difference was computed by the log-rank test.Results: 60 patients were included for the analysis. The median age was 37 years (range 15-83). 62% were male, 51% had B-symptoms, 56% had stage III/IV disease, 54% had elevated serum LDH, 29% had nodal involvement. The most frequent non-nasal sites were oropharynx, soft tissue, cutaneous, gastrointestinal and orbit with 24%, 17%, 12%, 7% and 5%, respectively. 79% patients received systemic chemotherapy, 7% received radiotherapy alone and 14% did not received chemotherapy because poor performance status. Of patients who received chemotherapy only 20% received a L-asparaginase-based chemotherapy. The median follow-up time was 8 months (1-103). The median overall survival (OS) was 14 months (interquartile range [IQR] 4-29), 1y OS was 51% (95% CI 33-67), 3y OS 21% (95% CI 7-40), 5y OS 14% (95% CI 3-34), figure 1. The median overall survival according to LDH level was 10 months regardless of the levels (p=0.84), figure 2. The median OS for female and male were 8 and 10 months, respectively p=0.59)Conclusions: Peruvian patients with non-nasal NKTCL are younger, with presence of B-symptoms, advance stage and elevated LDH levels compared to those reported in nasal NKTCL. The most frequent non nasal NKTCL is located on the oropharynx. OS of non-nasal NKTCL is extremely poor. Elevated LDH and sex are not prognostic factors for OS. A larger cohort and follow-up are needed to evaluate prognostic factors in this population. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Follicular Lymphoma in a Single Cancer Center and Validation of FLIPI, FLIPI2, PRIMA and POD24 in Non-Caucasian Patients from Peru

BackgroundFollicular lymphoma (FL) is the second most common non-Hodgkin lymphoma subtype seen in Caucasian countries. Recent data were published on FL from Latin America (LATAM), presenting information of 12 countries. However, this information is widely variable because of the diversity of the Latin population (Caucasian and mestizo individuals). Our aim was to evaluate the clinical features, treatment patterns outcomes of non-Caucasian patients with FL from a single cancer center. Our second aim was to validate FLIPI1, FLIPI2, PRIMA and POD-24 score in our cohort.Methods:This is a retrospective study, including all patients with a pathological diagnosis of FL at the National Institute of Neoplastic Diseases in Lima, Peru from 2010 to 2019. All cases were reviewed by specialized pathologists. Baseline clinical and pathological data were collected. Responses were assessed based on the Lugano criteria. Overall survival (OS) was estimated using the Kaplan-Meier method. Differences were compared with the log-rank test.ResultsFrom 2010 to 2019 4480 patients with B-cell lymphoma were diagnosed, 449 patients (10%) had grade 1 to 3A FL, 302 patients had the five variables for FLIPI, 242 for FLIPI2, 257 for the 2 variables for PRIMA prognostic index and 209 received systemic treatment and had enough information to evaluate POD24. The median age for the entire cohort was 59 years old (range 24-92), 49% of patients were ≥60 years, 46% were male, 22% had extranodal involvement, 34% had bulky disease (≥6 cm in diameter), 68% had stage III/IV disease, 32% had hemoglobin <12 g/dl, 8% had serum albumin <3 g/dl, 35% had elevated serum LDH, 33% had B2-microglobulin ≥3,5 mg/l, 22% had bone marrow involvement and 23% had lymph node sites >4. Low, intermediate and high FLIPI were seen in 39%, 27% and 34% of patients, respectively. Low, intermediate and high-risk FLIPI2 was seen in 23%, 54% and 23% of patients, respectively. Low, intermediate, and high PRIMA was seen in 53%, 12% and 35%, respectively. 209 patients received systemic treatment, 60% received CHOP ± rituximab (R), 13% CVP ± R, 15% CHOP, 11% CVP. Response data were available in 158 patients with complete response in 35%, partial response in 57% and no response in 8%, for an overall response rate of 92%. 19% of patient had disease progression within 24 months of first treatment initiation (POD24). For the entire cohort, the median follow-up time was 2.6 years (Interquartile range [IQR] 0.08-13.6), the median OS was not reached (IQR 4.2-not reached). 5y was OS 72% (95% CI 65-77). 5y OS for low, intermediate and high FLIPI were 90% (95% CI 81-94.5), 65% (95% CI 47.3-78.2) and 60.1% (95% CI 46.6-72.4), respectively (p<0.001; Figure a). 5y OS for low, intermediate and high FLIPI2 were 91.9% (95% CI 76.3-97.3), 75.4% (95% CI 63.8-83.7) and 52.9% (95% CI 35.5-67.6), respectively (p<0.001; Figure b). 5y OS for low, intermediate and high PRIMA were 80.5% (95% CI 70-87.6), 79.4% (95% CI 52-92), and 61% (95% CI 47-73), respectively (p=0.004; Figure c). Patients who had and did not have POD24 had median OS of 5.7 years (IQR 2-NR) and NR (IQR 5.1-NR), respectively (p<0.001). 5y OS for patients who had and did not have POD24 was 54.1 % (95% CI 31-63) and 75.2% (95% CI 66-82), respectively (p=0.01).Conclusion:FL has a lower incidence in non-Caucasian patients in Peru compared to those reported for Western countries or other LATAM Caucasian population. FL patients showed higher rates of high FLIPI and FLIPI2 than previously reported in the literature. Chemoimmunotherapy is the standard approach to FL patients, which is associated with high rates of overall response, but low rate of complete response. The OS rates are shorter than those reported in the previously LATAM cohort. Our study validates the prognostic value of FLIPI1, FLIPI2, PRIMA and POD24. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Pooled Analysis of First-Line Treatment with Targeted Agents in Patients with Chronic Lymphocytic Leukemia (CLL) Aged 80 Years and Older

Pooled Analysis of First-Line Treatment with Targeted Agents in Patients with Chronic Lymphocytic Leukemia (CLL) Aged 80 Years and Older

Long Term Outcomes of Adult Lymphoblastic Lymphoma Patients Treated with Pediatric Regimen in Brazil

Introduction: Lymphoblastic lymphoma (LBL) is a rare and aggressive neoplasm which is more common in children and young adults. The adoption of pediatric inspired regimens for acute lymphoblastic leukemia (ALL) increased response rates and improved overall survival (OS). Due to the rarity of this disease studies addressing specific outcomes of LBL, especially from Latin America, are lacking.Objectives: To report outcomes of adult newly diagnosed with LBL in our center, aiming to examine baseline factors associated with worse survival.Methods: Retrospective cohort study of patients diagnosed with LBL between 2002 and 2018 and treated with adapted-BFM (aBFM) regimen at Instituto do Cancer do Estado de São Paulo (ICESP). Patients with acute leukemia were excluded from this analysis. The aBFM protocol was based on the BFM-86 protocol and previously reported by our group (Pinheiro et al, 2006).Results: Over this period, 26 patients received aBFM protocol in our institution. Twenty patients had T-LBL (77%) and mostly male (n=18). Median age was 26 years (17-54). Fifty-four percent (n=9) had an advanced stage (III-IV) and 77% (n=20) had bulky disease at diagnosis, predominantly mediastinal (n=15). Bone marrow involvement occurred in 21% of cases (5/24) and CNS disease was found in 2 cases. Complete remission (CR) rate was 68% (17/25). Four out of 5 B-LBL cases did not achieve CR, showcasing the influence of immunophenotype on CR (p=0.04). Two patients died before response assessment. Nine patients underwent consolidation radiotherapy (RT), defined at the discretion of the physician. The remaining 2 cases received cranial RT for CNS involvement. At 5 years, overall survival (OS) was 47,3% (CI 95%, 29,5 - 75,6) and event-free survival (EFS) was 51,1% (CI 95%, 34,6 - 75,5). Univariate analysis showed that phenotype (B-cell, HR=4.3) and the hemoglobin level at the diagnosis (continuous, HR=0.78) were significantly associated with OS (Figure). Cumulative incidence of relapse was 36%, whereas non-relapse mortality was 12% in this cohort.Discussion: Current treatment of LBL is based on pediatric ALL protocols including CNS prophylaxis. Previous studies of LBL patients using pediatric inspired regimens had 3y OS of 69%, which is higher than that found in our study. Markedly, outcomes of patients with B-LBL were poor and notably, no genetic evaluation aiming to screen for BCR-ABL or Ph-like signature was performed in such cases. These genetic alterations are more common in Latin America and must be screened as they strongly impact on the management.Conclusions: Few studies encompassing adult LBL patients are available. To our knowledge, this is the first one from Brazil. Although this study carries several limitations, we can conclude that the use of aBFM is feasible and achieves acceptable response rates in the T-cell subset. By contrast, B-LBL cases fared poorly and further studies are needed to implement a better genetic characterization and newer treatment strategies. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Frailty Scale for Outcome Predictions in Hematopoietic Cell Transplanted Adults

INTRODUCTIONFrailty in patients undergoing hematopoietic cell transplantation (HCT) has a negative impact on survival. The inclusion of frailty evaluations before HCT is highly recommended; however, there is no consensus about the best methodology to evaluate this syndrome.In 2018 our center started a Frailty and Functionality program that involves regularly collecting information on the following eight indices in patients referred for allogeneic HCT (Salas et al., 2021): Clinical Frailty Scale (CFS), Instrumental Activities of Daily Living (IADL) test, Timed up and Go Test (TUGT), Grip Strength (GS), Self-Health Rated questionnaire (SHR-Q), Fall test, albumin (Alb), and C - reactive protein (CRP). With the recorded measurements of the eight indices and the corresponding validating process, we propose a HCT Frailty Scale. This scale is specifically designed to identify fit, pre-frail, and frail candidates for alloHCT, from better to worst probability of post-transplant survival.METHODSBetween June 2018 and December 2020, 338 adults underwent alloHCT at our Institution. Frailty syndrome was evaluated prospectively in all patients at first consultation, using existing resources, after informed consent. It included measurement of the eight indices. The median time to evaluate was 5-6 minutes. Each index was given a value of 0 if normal or 1 (abnormal). Complete data were available for 298 patients that were finally included in the analysis. With this data the HCT Frailty Scale was elaborated as follows.The study cohort was split in two groups, a training cohort with 2/3 (N=200) of the patients, and a validation cohort of 1/3 (N=98), proportional to death outcomes. With the data from the training group we estimated a multivariable Cox model with overall survival (OS) as dependent variable, and the eight referenced indices as explanatory variables. Any normal result was scored 0, and based on the estimated HR coefficient from the Cox model, a proportional weight score was given to each respective index variable in the calculation of the composite HCT Frailty Scale score. The HCT Frailty index was calculated using the following formula: 1.5 *CFS, +1*IADL, +1*GS, + 1.5*TUGT, + 1*SHR-Q, +1*Falls-Test, + 1.5 *Alb, + 2*CRP. As a result, the HCT Frailty Scale goes from 0 to 10.5. The values of the scale were grouped to determine the following three groups of patients: (a) Fit patent: scale score ≤1; (b) Pre-Frail patient: 1< scale score < 5.5; (c) Frail patient: scale score 5.5 (Figure 1).RESULTSBaseline characteristics of the training and validation cohort are shown in Figure 1. Of the 200 patients included in the training cohort, the median age was 58 years (range 19-76 years); 29 (15.85%) had a KPS between 70-80%; and 56 (30.11%) a HCT-CI >3.The elaborated HCT Frailty Scale classified the 200 patients as: (a) 70 (35%) fit patients with an estimated 1-y OS of 83.7%; (b) 97 (48.5%) pre-frail patients with a predicted 1-y OS of 75.6%; and (c) 33 (16.5%) frail patients with an estimated 1-y OS of 52.8%. Of the 33 frail patients, 54.8% had a KPS between 90-100% and 48.5% had an HCT-CI <3 and of the 70 fit patients, 4.8% had a KPS between 70-80% and 24.2% had an HCT-CI ≥ 3. These differences support the hypothesis that frailty does not necessarily correlate with performance and comorbidities. The predictive ability of the HCT Frailty Scale was validated in 98 patients included in the validation cohort. This scale identified (a) 33 (33.7%) fit patients with an expected 1-y OS of 90.3%, (b) 51 (52%) pre-frail patients with an expected 1-y OS of 69.5%, and (c) 14 (14%) frail patients with an estimated 1y OS of 46.2% (Figure 1).CONCLUSIONThe HCT Frailty Evaluation Scale has been specifically designed to be applied in routine clinical practice and to patients across all ages. The scale ranges from 0 to 10.5 and the score value is calculated as the weighted sum of values of eight indexes evaluated at first consultation. The proposed scale should be of utility to identify frail and pre-frail patients that may benefit from appropriate counselling pre-transplant and individualized interventions to reverse frailty syndrome prior to alloHCT. [Display omitted] DisclosuresLaw: Novartis: Consultancy; Actinium Pharmaceuticals: Research Funding. Kim: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Paladin: Honoraria, Research Funding; Bristol-Meier Squibb: Research Funding; Pfizer: Honoraria, Research Funding. Lipton: Bristol Myers Squibb, Ariad, Pfizer, Novartis: Consultancy, Research Funding. Mattsson: MattssonAB medical: Current Employment, Current holder of individual stocks in a privately-held company.

Long Term Clinical Outcomes With Dedicated Proton Ocular Beam and Helium Ion Radiation for Uveal Melanoma Patients Aged 45 and Younger

<h3>Purpose/Objective(s)</h3> Uveal melanoma (UM) is particularly rare and potentially devastating for patients ≤ 45 years old (yo). Limited long term data exist post-particle beam radiation (RT) for this age group and hence an in-depth analysis of clinical outcomes is presented. <h3>Materials/Methods</h3> Patients were identified in a single institution's prospectively maintained database (n = 2558) of eye treatment with proton beam radiation (PBRT, 1994-2020) and helium ion RT (1979-1992). All included patients were treated for UM. Post-local eyewall resection or salvage RT patients were excluded. Patients were aged ≤ 45 yo at radiation (PBRT, n = 247 and helium, n = 80). PBRT patients undergoing 56 GyE in 4 fractions (n = 240) were further analyzed for local control (LC), eye preservation, distant metastasis (DM), and overall survival (OS). Univariate analysis using the Kaplan-Meier method (log rank test) and multivariate regression analysis using Cox's proportional hazard model (likelihood ratio test) were performed. <h3>Results</h3> Median follow-up for PBRT pts was 85.7 months (3.0-317.5). Median age at RT was 38.3 years (13.3-45.9); tumor location was 87% choroidal, 11% ciliary body (CB), and 2% iris only; tumor height 4.4 mm (0.8-15.8), largest tumor diameter (LTD) 10.5 mm (2.1-25.1), distance to disc/fovea 3.1/1.9 mm. 5-year (y) LC was 95% and 10y 94%. Ciliary body (CB) tumors showed lower LC (<i>P</i> = 0.02). LTD was the one independent multivariate predictor of LC (<i>P</i> = 0.04). Three patients had very late local failures (LF), all showed spindle-cell features [time-to-LF 13.2, 16.1, 17.5 years]. 10y overall eye preservation was 83%. Enucleation risk decreased with greater tumor-disc distance (<i>P</i> = 0.0001). Improved eye preservation was noted with ≤ 50% dose to lens (<i>P</i> = 0.01), ≤ 20% CB (<i>P</i> = 0.02), disc (<i>P</i> = 0.004), macula (<i>P</i> = 0.03), and nerve (<i>P</i> = 0.009). Multivariate analysis identified nerve length receiving 50% dose (<i>P</i> = 0.0003) and tumor height (<i>P</i> = 0.0008) as significant independent predictors of enucleation. 10y DM-free rate was 81% and 10y OS was 83%. LTD was the most significant predictor of DM (<i>P</i> = 0.0001) followed by age > 30 vs ≤ 30 (<i>P</i> = 0.03). The age ≤ 30 subgroup (n = 44) had a 5y DM-free of 100%, and had only 2% CB tumors. Two of seven early (1994-1995) proton patients receiving 48 GyE in 4 fx, had LF. The helium cohort median follow-up was 160.9 months (23.9-292.8). Median age at RT was 37.2 (18.1-45.9), tumor height 6.2 mm (2.9-14), LTD 10.5 mm (5-25), distance to disc/fovea 3.8/3.0 mm, and 24% had tumors with ciliary body involvement. Median (range) for helium RT dose was 70 GyE (48-80). Helium cohort 10y LC was 99%, 10y eye preservation was 82%. <h3>Conclusion</h3> Excellent long-term local control (10y 94% PBRT and 99% Helium cohorts) and eye preservation is seen in UM patients aged ≤ 45 treated with proton and helium ion radiation. Specific clinical and dose-volume parameters may be utilized to assess patient prognosis.

OAB-052: Impact of chromosome 1 abnormalities on newly diagnosed multiple myeloma treated with proteasome inhibitor, immunomodulatory drug, and dexamethasone: analysis from the ENDURANCE ECOG-ACRIN E1A11 trial

<h3>Background</h3> Chromosome 1 abnormalities (C1A) are frequently identified in multiple myeloma (MM). We assessed impact of C1A in a post hoc analysis of E1A11 trial. <h3>Methods</h3> E1A11 randomized newly diagnosed (ND) MM patients (pts) with traditional ‘standard risk' features or t(4;14), not intended for upfront transplant, to bortezomib (V) or carfilzomib (K), in combination with lenalidomide (R) and dexamethasone (d), followed by indefinite or 2-year (y) R maintenance. Impact of C1A and ultra-high risk (UHR) MM [≥2 of the following: +1q [gain1q (3 copies) or amplification (amp)1q21 (≥4 copies)], deletion (del)1p and t(4;14)], was assessed. <h3>Results</h3> Of 1087 pts, 912 were evaluated for + 1q (gain1q or amp1q) and 774 for del1p. Gain1q, amp1q and del1p were noted in 23%, 7.5% and 9% pts, respectively. Best responses to VRd or KRd within each response category were similar, irrespective of +1q/del1p status. Within each arm, progression-free survival (PFS) was inferior for pts with +1q versus (v) pts without +1q; median 29 v 42 months (m) for both arms [VRd, HR 1.51 p 0.011; KRd, HR 1.63, p 0.002]. Corresponding 3y overall survival (OS) rates on VRd were 74 v 86% (HR 1.47, p 0.069) and 82 v 88% (HR 1.34, p 0.185) on KRd. Regarding copy number, pts with gain1q v those without +1q had inferior PFS with both VRd (median 29m, HR 1.59, p 0.012) and KRd (median 33m, HR 1.41, p 0.051). OS rates with gain1q were inferior within VRd arm only (3y 71%, HR 1.78, p 0.014; KRd 3y OS 89%, HR 1.02, p 0.93). By contrast, pts with amp1q, v pts without +1q, had inferior outcomes with KRd (median PFS 24m, HR 2.37, p<0.001; 3y OS 62%, HR 2.43, p 0.008) but not with VRd: median PFS 32m, HR 1.43; p 0.186; 3y OS 75%, HR 1.29; p 0.48). Pts with del1p, v those without del1p, had inferior PFS (median 29 v 39m; HR1.49, p=0.042) and OS rates (3y 74 v 85%, HR 2.03; p 0.003) in the entire cohort. Within KRd arm, the respective OS rates were comparable (3y, 87 v 86%, HR 1.10, p 0.818). By contrast, pts with del1p on VRd had inferior OS (3y 60 v 84%, HR 3.30, p<0.001). UHR MM pts had worst outcomes (median PFS, 20 v 38m, HR 2.01, p<0.001; 3y OS, 68 v 85%, HR 1.99, p 0.004). However, OS for UHR MM pts on KRd was similar to that of pts without UHR MM (3-yr, 87 v 86%, HR 0.95, p 0.902; VRd 3-yr, 45 v 84%, HR 4.15, p<0.001). Analyses of treatment effect within subgroups showed superiority of KRd over VRd for OS among pts with gain1q [HR 0.50 (0.28-0.90)], del1p [HR 0.34 (0.13-0.89)] and UHR MM [HR 0.18 (0.07-0.51)], but not amp1q [HR 1.56 (0.64-3.78)]. <h3>Conclusion</h3> Gain1q or amp1q portends poor outcome among NDMM pts treated with either VRd or KRd. Specifically, pts with amp1q as a sole high-risk abnormality have distinctly poor outcomes with KRd. By contrast, KRd, but not VRd, appears to abrogate the adverse impact of del1p. Given the limitations of the trial design and post hoc subset analyses, longer follow up and confirmatory studies are warranted for definitive conclusions.