Higher Number Of Pts Research Articles

Real-World Outcomes and Treatment Patterns in AL-Amyloidosis in Austria: An Analysis from the Austrian Interdisciplinary Amyloidosis Registry (AIDA)

Introduction This project aimed to provide an overview of the treatment landscape for AL - Amyloidosis (AL-A) in Austria as documented in AIDA, the Austrian Interdisciplinary Amyloidosis Registry. By examining the existing body of knowledge surrounding treatments and demographics, we seeked to shed light on the potential benefits and challenges for new treatment modalities in the context of AL-A. Methods We identified 210 AL- pts. from AIDA (cut off May 15, 2023). Statistics were descriptive. Kaplan Meier was chosen for survival plots and analyses were carried out with Excel and SPSS. Results We present data from 210 AL-A pts. recruited from AIDA. This constitutes 45.95% of all pts. in AIDA, with the major parts of the residual population made up by wt-ATTR amyloidosis pts. (47.48%), with some rare other amyloidosis subtypes accounting for the rest. There was a male pre-dominance in the cohort (62.38%) well in line with published data. Pts. with AL-A were found to be much younger (median age 66a vs. 78a) compared to pts. suffering from wt-ATTR. Diagnosis of AL-A was made between 1997 and 2023, with the median year of first diagnosis being 2016, resulting in median follow up in the cohort of ~ 7 years. The pattern of organ involvement by AL-A were quite typical with heart (78.6%), kidney (58.1%), GI-tract (23.3%) and PNS (21.4%) being the dominant manifestations. Advanced stages by either the classical Mayo staging, as well as the revised one were regrettably still by far more frequent at time of diagnosis as early disease stages (classical Mayo III in 65.8%, and revised MAYO III and IV in 27.8% and 42.3% of pts. respectively). This is mirrored in a high number of pts. with severe to moderate renal insufficiency (GFR < 30ml/min in 4.6% and between 30-60 ml/min in 42.2% of pts.) and/or moderate to severe cardiac involvement (NT-pro BNP > 5000 ng/l in 37.2%, and between 500 - 5000 ng/l in another 51.2% of pts.). Detailed data on comorbidities and toxicities will be added. Treatments Only 141/210 pts. ever received a documented 1 st line of treatment (LoT), of which only 35.5% received a 2 nd LoT, and even less a 3 rd LoT (20.6%), while more LoTs were applied only in a handful of pts. This horrendous attrition rate per LoT is far above, what has been described for Myeloma (20% / LoT). Time to next tretament was found to be median of 9.9 months. 54 pts. received a 1st LoT with the intent of pursuing an autologous stem cell transplantation (ASCT), but only 54% of these actually were transplanted. This compares inferior to Myeloma, although MM pts. are usually significantly older. The most frequently used therapeutic regimes were VCd-D (Andromeda) with or without Dara-maintenance. The widespread use of anti-CD38 based treatments in this sub-cohort is mirrored in a quite high rate of high-quality hematologic responses (CR+VGPR = 51.9%). 90 pts. received 1st LoTs not intending to lead to ASCT. Again, Daratumumab based regimes were the most used, but treatment outcomes were much inferior (hematologic CR+ VGPR = 18.9%) probably based on dosages, time on therapy, and not applied ASCT. Only 40 pts. received conventional 2nd LoTs usually classical Myeloma therapies, with modest treatment results. Even hematologic high-quality responses (CR+VGPR = 25%) were rare not to mention organ responses. Survival Median survival in the AIDA cohort was found to be 45 months. Broken down by Mayo stages, both classic and revised, was found to be quite unfavorable for advanced disease (14 months in revised Mayo stage IV or classical Mayo stage III). Conclusions Compared to other plasma cell dyscrasias overall outcomes in AL-A are still dismal, despite the introduction of recent effective anti-plasma cell therapeutics in the treatment algorithm. Disease modifying therapies are urgently needed and should be preferentially introduced in 1 st line, as only few pts. will receive 2 nd or later LoTs. Furthermore, efforts to improve awareness for this dreadful disease are urgently needed to enable more therapies to be applied in less advanced disease settings. Take home-messages: 1. Efforts needed to improve early diagnosis of AL-A when treatment options will not be hampered by progressive organ dysfunctions 2. Absolute necessity to explore disease modifying therapies going beyond stopping excess free light chain production 3. As only a limited number of pts. received multiple LoTs any new therapeutics should be integrated in effective 1 st LoTs preferentially.

REAL‐WORLD DURATION OF VENETOCLAX TREATMENT FOR CHRONIC LYMPHOCYTIC LEUKEMIA AND SMALL LYMPHOCYTIC LYMPHOMA

Introduction: Venetoclax (V) is an approved fixed-duration treatment (tx) for chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL), as a 12-cycle regimen (∼12 mos) with obinutuzumab (O) in the first-line (1L) setting or as a 24-cycle regimen (∼24 mos) with rituximab (R) in the relapsed/refractory (R/R) setting. We analyzed real-world tx patterns of V+O in 1L and V+R in R/R settings in patients (pts) with CLL/SLL in the United States. Methods: A retrospective cohort analysis was conducted using the IQVIA PharMetrics® Plus database to identify pts ≥18 y treated with V+O (1L cohort; May 2019 to September 2021) or V+R (R/R cohort; June 2018 to September 2021). Start of tx regimen was defined as the index date. All pts were required to have ≥1 diagnosis code for CLL/SLL and continuous enrollment 12 mos prior to and ≥3 mos after index date. Duration of tx (DoT) was defined as time from index date to earliest of either tx discontinuation (i.e., ≥60-d gap in V prescription refills) or censoring (i.e., end of follow-up). Fixed-duration tx cycle was defined as 12- or 24-cycle dosing (days 336−364 for 1L setting and days 707−735 for R/R setting, based on the dosing schedule plus 28 days). Kaplan-Meier analysis was used to estimate the probability of remaining on tx for the 1L and R/R cohorts. Results: A total of 116 pts in 1L setting (mean age, 62.3 y) and 145 pts in R/R setting (mean age, 64.2 y) were identified; 48.3% of R/R pts had prior targeted therapy. Median (95% CI) DoT in V+O pts (n = 115) was 12.4 (11.5, 13.4) mos over a median follow-up of 11.4 mos; probability of remaining on tx at 12, 18, and 24 mos was 56.4%, 20.2%, and 5.1%. Median (95% CI) DoT in V+R pts (n = 133) was 24.5 (13.4, 25.2) mos over a median follow-up of 15.5 mos; probability of remaining on tx at 24, 30, and 36 mos was 53.8%, 19.0%, and 19.0%. Among V+O pts, 47.8% (55/115) had ≥12 mos follow-up, of whom 9.1% had fixed cycles and 38.2% discontinued early (median DoT: 4.6 mos). Among V+R pts, 29.3% (39/133) had ≥24 mos follow-up, of whom 5.1% had fixed cycles and 46.2% discontinued early (median DoT: 7.1 mos). The remaining pts in each cohort had DoT >12 or 24 cycles (Table). Conclusions: While median DoT was approximately 12 mos for V+O-treated pts (1L setting) and 24 mos for V+R-treated pts (R/R setting), a high number of pts did not maintain the fixed-dosing schedule. This study provides evidence that a V-based approach may not be suitable for all pts with CLL/SLL. Encore Abstract—previously submitted to regional or national meetings (up to <1’000 attendees), EHA 2023 The research was funded by: AstraZeneca Keyword: Chronic Lymphocytic Leukemia (CLL) Conflicts of interests pertinent to the abstract A. Teschemaker Employment or leadership position: AstraZeneca Stock ownership: AstraZeneca S. Hakre Employment or leadership position: AstraZeneca Stock ownership: AstraZeneca J. Tse Research funding: AstraZeneca Pharmaceuticals. IQVIA received research funding from AstraZeneca to conduct this study. N. F. Shaikh Research funding: AstraZeneca Pharmaceuticals. IQVIA received research funding from AstraZeneca to conduct this study. Y. Gu Research funding: AstraZeneca Pharmaceuticals. IQVIA received research funding from AstraZeneca to conduct this study. A. Near Research funding: AstraZeneca Pharmaceuticals. IQVIA received research funding from AstraZeneca to conduct this study.

Abstract 961: HER2-low expression in patients with advanced or metastatic solid tumors

Abstract Introduction: HER2 protein expression by immunohistochemistry (IHC) has been the main testing method for breast and gastric cancers. Much remains unknown about the frequency of HER2-low (IHC 1+ or 2+) expression and the change of HER2 status from primary to metastatic tumor samples. There is limited data available about the HER2-low frequency in solid tumors beyond breast and gastric/gastroesophageal (GEJ) cancer. Methods: HER2 IHC was performed in 923 patients (pts) with metastatic breast and 51 pts with gastric/GEJ cancers in CLIA-certified labs. We evaluated the HER2 IHC in paired primary and metastatic samples in breast cancer. We also assessed the HER2 status in non-breast, non-gastric/GEJ histologies. In available cases, concurrent HER2 genomic alterations were evaluated. Results: A total of 867 pts with breast cancer had a definitive HER2 IHC score for their metastatic sample: 101 pts (11.6%) were 3+, 171 pts (19.7%) were 2+, 252 pts (29%) were 1+ and 343 (39.6%) had no HER2 expression. The HER2 IHC scores in metastatic samples as compared to primary was in concordance in 54.9% of cases, while HER2 3+ remained unchanged in 87.2%, kappa=0.85 with a 95% CI = (0.79, 0.91). In 48 cases with metastatic gastric/GEJ cancer, HER2 was: 3+ in 2 pts (4.2%), 2+ in 5 pts (10.4%), 1+ in 9 pts (18.8%) and 32 (66.7%) had no HER2 expression. In non-breast and non-gastric/GEJ cancers, HER2-low was found in 631 pts (33.5%) as shown in the table below. A total of 1,552 pts who had HER2 IHC also had genomic testing: 36 had HER2 activating mutations, 48 had HER2 amplification (amp) and 3 had HER2 amp and mutations. 22 of 33 pts with HER2 mutations (without amp) had HER2 IHC expression: 10 pts (30%) were 1+, 10 (30%) were 2+ and 2 (6%) were 3+. Conclusion: Our results show that HER2-low expression is frequently found across tumor types and HER2 activating mutations are enriched in cancers where HER2 is expressed. These findings suggest that a high number of pts with solid tumors with HER2-low expression could potentially benefit from HER2 directed therapies. HER2 expression in solid tumors Cancer Types HER2 expression levels (IHC) Total* 3+(N pts) 3+(%) 2+(N pts) 2+(%) 1+(N pts) 1+(%) 0 (N pts) 0 (%) Appendiceal 0 0 3 6 8 16 39 78 50 Cancer of Unknown Primary 2 4 8 15 15 28 29 54 54 Cholangiocarcinoma 5 4 15 12 35 29 67 55 122 Colorectal 19 3 46 8 118 20 394 68 577 Endometrial 16 13 49 39 10 8 52 41 127 Gallbladder 3 9 8 24 7 21 15 45 33 HNSCC 2 9 1 4 4 17 16 70 23 Salivary 6 13 10 21 14 29 18 38 48 Hepatocellular Carcinoma 0 0 8 25 6 19 18 56 32 Non-small cell lung cancer 6 3 31 15 68 33 100 49 205 Ovarian/Fallopian Tube 4 5 17 20 11 13 53 62 85 Pancreas 1 1 5 7 16 24 45 67 67 Prostate 0 0 0 0 4 13 27 87 31 Renal Cell Carcinoma 0 0 0 0 1 5 18 95 19 Sarcoma 0 0 1 3 1 3 35 95 37 Small Bowel Cancer 2 9 2 9 1 4 18 78 23 Thyroid 0 0 0 0 2 4 54 96 56 Urothelial Carcinoma 38 22 48 27 32 18 57 33 175 *more than 15 samples available; HNSCC=head and neck squamous cell carcinoma Citation Format: Burak Uzunparmak, Cara Haymaker, Gabriela Raso, Chen Zhu, Serena Masciari, Lei Wang, Bryce Kirby, Heather Lin, Aysegul Gorur, Ann-Marie Cimo, Amber Kennon, Qingqing Ding, Andrea Palmieri, Gabriele Elizabeth Urschel, Ying Yuan, Guoxin Feng, Yasmeen Rizvi, Aisha Hussain, Vivek Subbiah, Timothy Anthony Yap, Jordi Rodon-Ahnert, Sarina Anne Piha-Paul, David S. Hong, Funda Meric-Bernstam, Ecaterina E. Dumbrava. HER2-low expression in patients with advanced or metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 961.

Disease characteristics and clinical practice of BRAF V600E-mutant metastatic colorectal cancer treatment: Baseline analysis of patients enrolled in the BERING CRC study.

34 Background: BRAF V600E-mutant metastatic colorectal cancer (mCRC) is associated with a poor prognosis and limited clinical data. Based on results from the BEACON CRC trial, targeted treatment with encorafenib plus cetuximab (E+C) is available as a standard of care for these patients (pts) after prior systemic therapy. Since data from controlled clinical trials are based on a selected patient population, the non-interventional study (NIS) BERING CRC observes a broader patient population in clinical practice. Methods: BERING CRC is the first NIS investigating the use of E+C in clinical practice of BRAF V600E-mutant mCRC treatment after prior systemic therapy in Germany, Austria, and Switzerland. For the present analysis, disease characteristics and treatment data of the initial 81 pts were documented in 44 sites across Germany and Austria between 09/2020 and 04/2022. BERING-CRC is ongoing and aims to enroll up to 300 pts from 126 German, Austrian, and Swiss sites. The study observes pts treated according to the approved respective Summary of Product Characteristics (SmPC). The primary endpoint is the 1-year overall survival rate. Secondary endpoints include efficacy, QoL, and tolerability of E+C. Results: 81 pts were included in this baseline analysis. Median age was 67 years (range 34-88) and 48% were female. 48 pts (59%) were documented with right-sided tumors and for 62% stage IV disease was noted at initial diagnosis. In the metastatic setting, main sites of metastasis were liver, peritoneum, and lung (52%, 32%, and 22% of pts, respectively), with 16% of pts having ≥ 3 sites documented. For 30% of pts, an ECOG performance status (PS) of 0 was documented at baseline assessment (57% ECOG PS 1 or 2). Adjuvant treatment was reported for 22 pts while relapse ≤ 6 months was documented for 10 of them. Consistent with BEACON CRC, adjuvant systemic therapy with relapse within ≤6 months was counted as metastatic 1st line treatment. 91% of pts with adjuvant treatment received chemotherapy alone in this setting. 4 pts (5%) were documented with E+C treatment directly following adjuvant therapy and 55% of all pts with documented first-line treatment (69 pts) received chemotherapy alone (CT), for 35% chemotherapy was combined with targeted therapy (CT+TT), 3% received immunotherapy, and 1% received TT alone. In second-line, 71% of pts with documented treatment received E+C (7% CT, 16% CT+TT). An initial bi-weekly cetuximab dosing was reported for 10% of pts treated with E+C. Conclusions: While the high number of pts with right-sided tumors was in line with previous findings on BRAF V600E-mutant mCRC pts, synchronous metastasis was reported considerably more often in this real-world cohort. As complementation to previous controlled clinical trial data, pts enrolled in BERING-CRC were notably older and presented with higher ECOG PS compared to the pivotal study. Clinical trial information: NCT04673955 .

Safety and efficacy of prophylactic pegfilgrastim on day 3 of neoadjuvant DCF chemotherapy in elderly patients with resectable esophageal cancer.

375 Background: Neoadjuvant chemotherapy with docetaxel, cisplatin plus 5-FU (Neo DCF) is one of the standard treatment for resectable esophageal cancer (EC) based on the results of the JCOG1109 study, however, a high frequency (5-30%) of febrile neutropenia (FN) has been reported with NeoDCF and the elderly (patients) pts have higher risk for FN. A single arm phase II study indicated that use of primary prophylactic pegfilgrastim (PG) on day 3 of NeoDCF might prevent FN. We compared the frequency of neutropenia and FN with or without primary prophylactic administration of PG on day 3 of NeoDCF in elderly resectable EC pts. Methods: EC pts who had received NeoDCF between 2009 and 2022, were ≥70 years old, and had adequate organ functions and PS were selected for this retrospective study. Pts were divided into two groups with Day 3 PG-containing DCF (day3 prophylactic PG: D3PG) or No PG DCF (non-prophylactic PG: NPG). Three courses of DCF (DTX [day 1]: 70 mg/m2, CDDP [day 1]: 70 mg/m2, 5-FU [continuous infusion on days 1-5]: 750 mg/m2, every 3 weeks) were planned, and prophylactic antibiotics was administered on days 5-15 in each group if possible. We retrospectively evaluated the relative dose intensity (RDI), histopathological and clinical benefit, and adverse events. Results: A total of 67 pts (D3PG, 32; NPG, 35) with a median age of 73 years were identified. The PS (0/1/2) and clinical stage (I-II/III/ IVA-B [only supraclavicular lymph node]) were 18 (56.3%)/12 (37.5%)/2 (6.2%) and 1 (3.1%)/18 (56.3%)/13 (40.6%) in the D3PG group and 20 (57.1%)/15 (42.9%)/0 and 7 (20.0%)/24 (68.6%)/4 (11.4%) in the NPG group, respectively. Six pts in the D3PG group and 3 pts in the NPG group discontinued NeoDCF because of toxicity and progression. All pts except 1 in the D3PG group underwent surgery. The RDIs (DTX/CDDP/5-FU) were 0.90/0.83/0.90 in the D3PG group and 0.83/0.83/0.83 in the NPG group. Pts who achieved a pCR (D3PG/NPG) were 7/3 (22.6%/28.6%). The common grade ≥3 adverse events (D3PG/NPG) were neutropenia (12.5%/71.4%) and FN (6.3%/20.0%). Three-year relapse-free survival rate (D3PG/NPG) was 70.8%/54.4% (hazard ratio [HR] 0.525 [95% confidence interval (CI) 0.189-1.457], p=0.216). Three-year survival rate (D3PG/NPG) was 91.8%/70.5% (HR 0.497 [95%CI 0.104-2.35], p=0.378), respectively. Conclusions: The use of primary prophylactic PG on day 3 of preoperative DCF improved the safety and maintained the RDI in the D3PG group. The efficacy was comparable between the D3PG and NPG groups despite the higher number of pts with more advanced disease in the D3PG group.

Clinical Characteristics and Overall Survival Among Acute Myeloid Leukemia (AML) Patients with TP53 Gene Mutation (TP53m) or Chromosome 17p Deletion (17p del)

Introduction TP53m is observed in 5%-15% of newly diagnosed AML patients (pts) and represent a poor prognostic group that is highly refractory to available treatment, both intensive and non-intensive, including venetoclax-based therapies. Currently there are no established therapies specifically targeting TP53m in AML. Better understanding of the outcomes in TP53m AML pts with standard-of-care treatments can provide important insights for clinical management and drug development. Methods Adult (≥18 years [yrs]) pts with new AML diagnosis from January 1, 2014 to February 28, 2021 were included from the nationwide Flatiron Health electronic health record-derived de-identified database. Prior to first line (1L) therapy start, all pts had TP53m determined from molecular tests or 17p del identified by cytogenetic/fluorescent in situ hybridization. Pts who received prior anti-leukemic therapies (except hydroxyurea, oral etoposide) or who had concurrent malignancies were excluded. Pts receiving 1L therapy were divided into 3 cohorts: hypomethylating agents (HMA; azacitidine/decitabine) and venetoclax (Cohort A), intensive chemotherapy (Cohort B), or HMA without venetoclax (Cohort C). Median overall survival (mOS) was estimated using Kaplan-Meier method. Baseline and clinical characteristics can impact treatment choice and survival in each cohort. Multivariate Cox proportional hazards models (including age, time to 1L therapy, comorbidities, TP53m status and cytogenic risk level, presence of 17p del, secondary and therapy-related AML, healthcare practice type, ECOG score, and post-1L allogeneic stem cell transplantation [allo-SCT]) were used to compare OS among treatment cohorts. Results A total of 370 AML pts with either TP53m (n=124) or 17p del (n=166) or both (n=80) were included. Median age was 72 (range 24-84) yrs, and majority were male (59%) and white (69%). Most pts (85%) were from community oncology clinics. Overall median follow-up time for all pts was 6 (range 0-74) mos and was similar for the three cohorts (6, 7, and 5 mos for Cohort A, B, and C, respectively). Although cytogenetic risk category information was missing for more than one-third (34%) of pts, majority (65%) belonged to the ELN 2017 adverse cytogenetic risk category. Deletions in chromosomes 5, 7, or 17 were reported in 88% (n=324) of pts, with 68% having more than one deletion. Secondary AML was reported for 118 (32%) pts, of which 92 (78%) had prior myelodysplastic syndrome; 38 pts (10%) had therapy-related AML. Bone marrow (BM) blasts were ≤30%, 31-50%, and >50% in 41%, 24%, and 29% of pts, respectively. Treatment Cohort A, B, and C included 94 (25%), 135 (37%), and 141 (38%) unique AML pts, respectively. Pts in Cohort A and C were older (median 75 and 77 yrs vs 62 yrs for Cohort B) and had more comorbidities (65% and 60% vs 40% in Cohort B with at least one comorbidity). BM blast clearance post-1L was reported in 54% of pts (115/215) overall and 67% (38/57), 62% (68/110), and 19% (9/48), with median duration of blast clearance of 6.3, 6.9, and 5.4 mos for Cohort A, B, and C, respectively. Only 30 pts (8%) received allo-SCT (5%, 16%, and 3% in Cohort A, B, and C, respectively). Death during follow-up was reported in 80% (n=294) of pts with mOS of 7.3 mos (95% confidence interval [CI] 6.5-8.3). mOS estimate was 7.4 mos (95% CI 6.0-8.8) for Cohort A, 9.4 mos (95% CI 7.2-10.4) for Cohort B and 5.9 mos (95% CI 4.3-7.5) for Cohort C. Survival was much higher in pts receiving allo-SCT, which only few pts in each cohort received (Table). Addition of venetoclax to HMA (Cohort A) did not improve OS compared with HMA only (Cohort C) in an adjusted Cox model (adjusted hazard ratio [aHR]=0.9, 95% CI 0.7-1.3). In a similar analysis, no difference in OS was observed between Cohort A and B (aHR=0.9, 95% CI 0.6-1.4). Conclusions In this large cohort of AML pts with TP53m/17p del, poor OS is observed with current standard-of-care treatment options. Pts treated with venetoclax and HMA combination did not have significantly different OS compared with pts treated with HMA only or pts receiving intensive chemotherapy. Younger age, fewer comorbidities, and higher number of pts receiving allo-SCT could have influenced apparent longer OS in the intensive chemotherapy cohort that was no longer significant in an adjusted model. Despite recent advances, TP53m AML pts continue to experience poor outcomes highlighting the significant unmet medical need and the need for novel therapies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Efficacy of a nurse monitoring service at preventing disease- or therapy-related symptoms in patients receiving targeted therapy or immunotherapy.

12118 Background: The safety profile of Targeted therapies (TT) and immunotherapy (IT) may be underestimated and negatively affect the clinical outcome. Methods: A nationwide, randomized, open-label trial (NCT04726020) conducted among 29 Italian centers involved two cohorts of 223 adult patients (pts) with a solid tumor, receiving TT (group B, 119 pts) or IT (group C, 104 pts). Pts were randomized to receive a weekly nurse monitoring phone call, together with an educational leaflet with some practical advice about toxicities (experimental arm), or only the educational leaflet (control arm). In the experimental arm, pts received their monitoring phone call before their treatment began, then every week for up to 16 weeks of treatment were completed. The primary objective was the evaluation of the difference in toxicities according to patient-reported outcome (PRO)-CTCAE. Results: Both arms were comparable in terms of pts’ characteristics (e.g. site of primary tumor, line of treatment). The adherence to the project (that is the completion of every expected call) was 62.1% in group B and 66.9% in group C. In group B, in the experimental arm, we found a higher number of pts without pain (53.7 vs 39.9%, p = 0.047); a trend of lower fatigue (29.2 vs 18%, p = 0.067) was also observed. In group C, a higher number of pts did not report fatigue (29.1 vs 17.5%, p = 0.043), shortness of breath (61.4 vs 38.5%, p = 0.002) or dry skin (72 vs 52.3%, p = 0.004). More pts also referred to be without pain (51.6 vs 38.8%, p = 0.065) and pruritus (75.9 vs 64.5%, p = 0.088), even if these difference were not statistically significant. Conclusions: The use of PRO assessment through active nurse monitoring might lead to a better tolerance of TT and IT with possible implications on pts’ quality of life and ultimately on treatment outcome. In particular, in the IT group, several symptoms were prevented from occurring, thus encouraging a major effort to implement such active monitoring in this population. Clinical trial information: NCT04726020.

Baseline characteristics of patients enrolled in the BERING CRC study: A European real-world study in BRAF V600E-mutant metastatic colorectal cancer.

e15584 Background: BRAF V600E-mutant metastatic colorectal cancer (mCRC) is characterized by a poor prognosis and limited clinical data. Based on results from the phase 3 BEACON CRC trial, targeted treatment with encorafenib plus cetuximab (E+C) represents a newly approved standard of care for these patients (pts) upon systemic therapy. As data from controlled clinical trials are based on a selected patient population, the non-interventional study (NIS) BERING CRC observes a broader patient population under real-world conditions. Methods: BERING CRC is the first NIS to investigate the real-world use of E+C in BRAF V600E-mutant metastatic colorectal cancer upon systemic treatment in Germany, Austria, and Switzerland. For the present baseline analysis, disease characteristics and treatment data of the initial 40 pts were documented prospectively in 27 sites across Germany and Austria between 09/2020 and 08/2021. As BERING-CRC is ongoing, the study aims to enroll up to 500 pts from 96 German, Austrian, and Swiss sites. The study observes pts treated according to the approval as given in the respective Summary of Product Characteristics (SmPC). The primary objective is to analyze the 1-year overall survival rate. Secondary endpoints include efficacy, quality of life and tolerability of E+C. Data are analyzed descriptively using standard summary statistics. Results: 40 pts were included in this baseline analysis. The median age was 68 years (range 34-88) and 38% were female. 26 pts (65%) were documented with right-sided tumors and for 63% stage IV disease was noted at initial diagnosis. In the metastatic setting, the main sites of metastasis were liver, peritoneum, and lung (55%, 40%, 33% of pts, respectively), with 20% of pts having ≥ 3 organs involved. For 38% of pts, an ECOG performance status (PS) of 0 was documented at baseline assessment (60% ECOG PS 1 or 2). Adjuvant treatment was reported for 8 pts and 88% received chemotherapy alone in this setting. 3 pts (8%) were documented with E+C treatment directly following adjuvant therapy and half of all pts with documented first-line treatment received chemotherapy alone (CT), for 42% chemotherapy was combined with targeted therapy (CT+TT). In second-line, 74% of pts with documented treatment received E+C (9% CT, 17% CT+TT). Bi-weekly cetuximab dosing was reported for 11% of pts treated with E+C. Conclusions: While the high number of pts with right-sided tumors was in line with previous findings on BRAF V600E-mutant mCRC pts, considerably more pts were male in this initial real-world cohort and synchronous metastasis was reported markedly more often. As complementation to previous controlled clinical trial data, pts enrolled to date in BERING-CRC were notably older and presented with higher ECOG PS compared to the pivotal study. Clinical trial information: NCT04673955.

Real-world efficacy of ribociclib (RIB) plus aromatase inhibitor (AI)/fulvestrant (FUL), or endocrine monotherapy (ET), or chemotherapy (CT) as first-line (1L) treatment (tx) in patients (pts) with hormone receptor–positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC): Results of fourth interim analysis (IA) from RIBANNA.

1065 Background: RIBANNA is a real-world, noninterventional study conducted in Germany evaluating efficacy, safety, and tolerability of RIB in combination with AI/FUL aiming to gain insights into routine clinical practice for pts with HR+, HER2– ABC. Here, we present results of the fourth IA from RIBANNA. Methods: Pre-, peri- and postmenopausal pts who received 1L tx with RIB+AI/FUL, or ET or CT for HR+, HER2– ABC were included in accordance with the German tx guideline. The effect of baseline demographic characteristics, including histological grade, age, previous adjuvant tx, Eastern Cooperative Oncology Group-performance score (ECOG-PS), and metastatic sites on progression-free survival was evaluated using Cox regression model. Results: At data cutoff October 11, 2021, 2598 pts were enrolled in the study (RIB+AI/FUL, n = 2177; ET, n = 239; CT, n = 182). Data from 1L tx were available for 2492 pts (95.9%), second-line tx for 689 pts (26.5%), third-line tx for 263 pts (10.1%), and fourth-line tx for 94 pts (3.6%). Significant differences were observed in baseline mean age and metastatic sites for pts in RIB+AI/FUL cohort vs ET and CT cohorts (both &lt; 0.001). At baseline, the mean (SD) ages of pts were 65.5 (11.6), 70.7 (11.5) and 61.6 (11.6) years in RIB+AI/FUL, ET, and CT cohorts, respectively. While comparing the performance status, 44.2% of pts in RIB+AI/FUL, 34.7% of pts in ET and 42.1% of pts in CT cohort were fully active with ECOG-PS = 0. CNS, liver, or lung metastases were recorded in 42.6% of pts in RIB+AI/FUL, 26.8% of pts in ET and 67.1% of pts in CT cohort. Bone only metastases were reported in 30.8%, 47.9% and 15.0% of pts in RIB+AI/FUL, ET, and CT cohorts, respectively. Overall, 32.1%, 37.7%, and 52.7% of pts discontinued the study in RIB+AI/FUL, ET, and CT cohorts, respectively, the most common reasons being deaths (16.1%,17.2%, and 31.9%, respectively) and lost to follow-up (5.9%, 8.8%, and 9.3%, respectively). The most common tx-emergent adverse event (grade 3 or 4) observed in RIB+AI/FUL cohort was neutropenia (14.8%), while 6.6% and 6.9% of pts in ET and CT cohorts, respectively, experienced neutropenia. The efficacy results from all 3 cohorts, including Kaplan-Meier curves, will be presented during ASCO 2022. Conclusions: RIBANNA study showed diverse population characteristics among pts who received RIB tx in a real-world setting. Overall higher number of pts were treated in 1L with RIB+AI/FUL followed by ET and CT. The differences in baseline characteristics on metastatic pattern, age, and ECOG-PS reflect different selection strategies for 1L tx decision. No new safety signals were identified. Clinical trial information: CLEE011ADE03.

Outcomes of classic Hodgkin lymphoma, relapsed within one year of diagnosis, in the era of novel agents.

7515 Background: Primary refractory disease (PRD) and early relapse (ER) are predictors of poor prognosis in classic Hodgkin lymphoma (cHL). In this multicenter retrospective study, we describe outcomes of PRD and ER in pts with relapsed/refractory (R/R) cHL treated with salvage therapy (ST) and autologous stem cell transplant (ASCT). Methods: Of 14 sites, adult patients with R/R cHL who received ST and underwent ASCT were enrolled. PRD was defined as progression on frontline chemoimmunotherapy or within 6 months of diagnosis. ER was defined as relapse from 6 months-1 yr of diagnosis. Pts who relapsed &gt;1 yr of diagnosis were called late relapses (LR). Study objectives were Overall response rates (ORR), CR rates, PFS, and OS. Results: Of 986 total pts, 160 had PRD, 365 had ER and 461 had LR. Significantly higher number of pts with PRD, but not ER, had bulky disease (41% vs 27%, p&lt;0.01) and B symptoms (53% vs 38%, p&lt;0.001) than LR. Higher proportions of pts with PRD and ER required &gt;1 line of ST (44% vs 30% vs 23%, p&lt;0.001) before ASCT and received BV maintenance (25% vs 24% vs 16%, p&lt;0.05). When adjusted for B symptoms and Bulky disease, PRD and ER had significantly lower ORR (65% vs 76% vs 84%, p&lt;0.001) and CR (37% vs 46% vs 57%, p&lt;0.001) to first ST than LR. Pts with PRD and ER had significantly lower PFS (56.3%, 61.4%, vs 77.6%, p&lt;.0001) and OS (93% vs 89% vs 94%, p=0.01) than LR. In pts with ER, Brentuximab/bendamustine (BBV) and brentuximab vedotin/nivolumab (BV/nivo) had a trend towards higher ORR (92% vs 92% vs 75%) but significantly higher CR (79.2% vs 76% vs 42%, p&lt;0.01) than platinum based chemotherapy (PBC). In pts with PRD, BBV and BV/Nivo had a statistically insignificant trend towards higher ORR and CR than PBC. The table shows 2 yr PFS by type of ST in PRD, ER, LR. There was no difference in PFS by time to relapse in BV/nivo, CPI and miscellaneous agents. BV/Nivo had a significantly higher PFS than PBC in PRD (88% vs 48%, p&lt;0.05) and ER (95% vs 57%, p&lt;0.05). There was no difference in PFS of PBC and other ST in PRD, ER or LR. OS was not significantly associated with type of ST in either group. Conclusions: PRD and ER are associated with lower response to ST and survival after ASCT compared to late relapse. In pts with PRD and ER, BV/Nivo has high ORR and CR and leads to significantly higher PFS comparable to pts with late relapse and may be preferable ST regardless of time to relapse. [Table: see text]

Efficacy of prophylactic pegfilgrastim on day three of preoperative DCF chemotherapy in elderly patients with resectable esophageal cancer.

305 Background: Preoperative neoadjuvant chemotherapy with cisplatin plus 5-FU (CF) is the standard treatment for resectable esophageal cancer (EC). Docetaxel plus CF (DCF) is also a promising preoperative treatment; however, a high frequency (5%-30%) of febrile neutropenia (FN) has been reported in patients (pts) receiving DCF, and elderly pts reportedly have a high risk of FN. The use of primary prophylactic pegfilgrastim (PG) on day 3 of DCF in resectable EC pts might prevent FN. We conducted a retrospective review to assess the efficacy of primary prophylactic PG administration on day 3 of preoperative DCF in elderly pts with resectable EC. Methods: EC pts who had received preoperative DCF between 2009 and 2021, were ≥70 years old, and had adequate organ functions and an adequate PS were eligible for this retrospective study. Pts were assigned to receive either PG-containing DCF (day3 prophylactic PG: D3PG) or standard DCF (non-prophylactic PG: NPG). Three courses of DCF (DTX [day 1]: 70 mg/m2, CDDP [day 1]: 70 mg/m2, 5-FU [continuous infusion on days 1-5]: 750 mg/m2, every 3 weeks) were planned, and antibiotic prophylaxis was mandatory on days 5-15 in each group. In the D3PG group, PG was administered subcutaneously on day 3. We retrospectively evaluated the relative dose intensity (RDI), histopathological efficacy, and adverse events (CTCAE ver5.0). Results: A total of 52 pts (D3PG, 17; NPG, 35) with a median age of 72 years were identified. The PS (0/1/2) and clinical stage (I/II/III/IVB [only supraclavicular lymph node]) were 10 (58.8%)/5 (29.1%)/2 (11.8%) and 0/1 (5.9%)/10 (58.8%)/6 (35.4%) in the D3PG group and 20 (57.1%)/15 (42.9%)/0 and 2 (5.7%)/5 (14.3%)/24 (68.6%)/4 (11.4%) in the NPG group, respectively. Three pts discontinued treatment because of toxicity (FN and nausea in D3PG and FN and diarrhea in NPG) and progression in each group, and all the pts underwent surgery. The RDIs (DTX/CDDP/5-FU) were 0.870/0.862/0.871 in the D3PG group and 0.833/0.829/0.830 in the NPG group. Five (29.4%) pts in the D3PG group and 10 (28.6%) in the NPG achieved a pCR. The common grade ≥3 adverse events (D3PG/NPG) were leukopenia (17.6%/51.4%), neutropenia (11.8%/71.4%) and FN (5.9%/20.0%). Conclusions: The use of primary prophylactic PG on day 3 of preoperative DCF improved the treatment safety treatment in elderly pts with resectable EC. No significant differences in treatment efficacy were seen between the D3PG and NPG groups despite the higher number of pts with a worse general condition or more advanced disease in the D3PG group than in the NPG group.

Propensity Score Matching Analysis Comparing Ruxolitinib Vs Historical Controls in 2 nd Line or Beyond Treatment for Chronic Gvhd after Therapy Failure

Propensity Score Matching Analysis Comparing Ruxolitinib Vs Historical Controls in 2 nd Line or Beyond Treatment for Chronic Gvhd after Therapy Failure

Real-World Evaluation of the Treatment Landscape for Chronic Lymphocytic Leukemia

Introduction:The treatment paradigm of chronic lymphocytic leukemia (CLL) has changed significantly with the introduction of targeted oral therapies, including Bruton's tyrosine kinase inhibitors (BTKis) and B-cell lymphoma 2 inhibitors (Bcl-2is). As more therapies enter the clinic, real-world data (RWD) are important to understand changes in the CLL treatment landscape and describe treatment patterns, to guide decisions on treatment strategies.Methods:This retrospective analysis used 2 RWD sources. Patients (pts) diagnosed with CLL and treated with chemotherapy, CD20 monoclonal antibodies (mAbs), BTKis, or Bcl-2is were studied in the Optum Clinformatics® Data Mart (CDM), a de-identified US administrative claims database. Pts in the CDM analysis received at least 1 prescription for or administration of a treatment of interest between 2016 and 2020 Q2, and a diagnosis of CLL within 12 months (mo) of treatment start. Cross-sectional annual cohorts were used to understand changes in treatment mix over time, and longitudinal cohorts were formed to identify treatment patterns. Medication adherence was assessed with persistence at 12 mo using a 60-day gap and proportion of days covered (PDC) at 12 mo. Electronic health records from oncology practices were extracted through December 2020 from the COTA real-world evidence database. Adults diagnosed with CLL/small lymphocytic lymphoma and treated with BTKis and/or Bcl-2is were included. Treatment discontinuation was assessed using physician-documented treatment dates and reasons for discontinuation, and overall duration of treatment with targeted therapy was assessed using Kaplan-Meier analysis.Results:In CDM, annual treatment rate among pts diagnosed with CLL increased from 16% (1788/10911) in 2016 to 26% (2441/9349) in 2020. The proportion of pts treated with BTKis and Bcl-2is increased from 40% (2016) to 65% (2020) and <1% (2016) to 13% (2020), respectively; corresponding decreases in the use of chemotherapies and CD20 mAbs were observed (Figure 1A). In pts initiating BTKis, most pts were not previously treated (937/1438; 65%); the most common initial regimens were BTKi monotherapy (mono) (1367/1438; 95%) and BTKi + CD20 mAb (54/1438; 4%). Few pts switched from BTKi mono to CD20 mAb mono (43/1367; 3%) or added CD20 mAb to BTKi mono (44/1367; 3%) within 12 mo. In pts initiating Bcl-2is, most received prior treatment (169/198; 85%); most common regimens were Bcl-2i mono (159/198; 80%), Bcl-2i + CD20 mAb (31/198; 16%), and Bcl-2i + BTKi (8/198; 4%). Among pts initiating Bcl-2i mono, 30% (48/159) added CD20 mAb within 12 mo; among pts initiating Bcl-2i + CD20 mAb, 94% (29/31) switched to Bcl-2i mono within 12 mo. Persistence at 12 mo was similar for BTKis (899/1438; 63%) and Bcl-2is (120/198; 61%) and mean (SD) PDC was similar for BTKis 0.69 (0.31) and Bcl-2is 0.68 (0.29). In COTA, 469 pts treated with BTKis and/orBcl-2is were included. More pts initiated BTKis as first-line (1L) (185/449; 41%) compared with Bcl-2is (13/109; 12%). Among pts initiating targeted therapy as 1L, most pts (81%; 149/185) initiated BTKi mono. Discontinuation rates were high for pts receiving BTKis (62%; 279/449) and Bcl-2is (61%; 67/109). Among BTKi discontinuers, toxicity (54%; 150/279) was the most common reason for discontinuation, followed by disease progression (12%; 34/279) (Figure 1B). Among Bcl-2i discontinuers, toxicity (36%; 24/67) was the most common reason for discontinuation, followed by completion of regimen (30%; 20/67) (Figure 1C). Median duration of treatment was 777 days (95% CI: 632-920) for the BTKis group and 639 days (95% CI: 335-755) for the Bcl-2is group. Median treatment duration in days was comparable between mono and combination regimens in both BTKis (782 vs. 809) and Bcl-2is (747 vs. 718) groups.Conclusions:RWD show standard of care shifted from chemoimmunotherapy to targeted therapies. Pts receiving targeted therapies had high rates of discontinuation, most commonly due to toxicity. Most targeted regimens were mono; more BTKi pts were treatment naive compared to Bcl-2i pts. Slow adoption of fixed-duration therapy with the Bcl-2i combination regimen was observed. The duration of Bcl-2i mono was comparable to that of the Bcl-2i combination regimens, and a high number of pts initiating combo regimens continued on mono regimens in contrast to regimens studied in randomized controlled trials. [Display omitted] DisclosuresSmith: Novartis: Current Employment; Pfizer: Ended employment in the past 24 months. Owusu: Novartis: Current Employment; Roche: Ended employment in the past 24 months. Wormser: Roche: Current equity holder in publicly-traded company; Novartis: Current Employment, Current equity holder in publicly-traded company. Woo: Novartis: Current Employment, Current equity holder in publicly-traded company.

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation from HLA-Identical Siblings Versus Unmanipulated Haploidentical Donors in Relapsing or Refractory Acute Myeloid Leukemia: A Retrospective Study from the ALWP of the EBMT

▪Introduction: Primary refractory or relapsing acute myeloid leukemia (R/R-AML) has very poor prognosis. Allogeneic hematopoietic stem cell transplantation (HSCT) may be the only chance of cure. Therefore a suitable donor should be rapidly searched for, in this setting. In those patients (pts) lacking an HLA-matched sibling donor (MSD), mismatched family donor (haploidentical, Haplo) may represent a valid and rapidly available option.Methods: Herein, we compared the outcomes of pts with R/R-AML undergoing first HSCT from either a MSD (n=1654) or Haplo (n=389) in the period 2007-2015. The Haplo group included pts receiving a T-repleted graft with post-transplant cyclophosphamide (PTCY, n=278), in vivo T-cell depletion (TCD, n=95), or both (n=16).Results: Median age at HSCT was 52 (range 18-74) years. Median follow-up was 16 and 22 months for MSD and Haplo recipients, respectively (p=0.11). At time of HSCT, 41% and 56% presented a primary refractory AML in Haplo and MSD groups, respectively (p<0.01). Compared to MSD, Haplo HSCT were performed more recently (median year 2013 versus 2011, p<0.01) with a higher number of pts having a poor Karnofsky performance status (22% versus 16%, p<0.01) and a positive serology for CMV (83% versus 71%, p<0.001) at time of HSCT, respectively. The latter also had more frequently undergone a previous autologous HSCT (8% vs 3%, p<0.01), had a longer interval from diagnosis to HSCT (7 versus 5 months, p<0.01), received more frequently bone marrow as stem cell source (47% vs 8%, p<0.01), a reduced intensity conditioning regimen (50% vs 43%, p<0.03), and a graft from a male donor (59% versus 53%, p<0.03) as compared to MSD recipients. Compared to Haplo, cumulative incidence (CI) of neutrophil engraftment was higher (93% versus 83%, p<0.01) and associated to a shorter median time to engraftment (15 versus 18 days, p<0.01) in MSD recipients. According to donor type, no differences were found in univariate analysis for the CI of grade II-IV acute graft-versus host disease (aGVHD)(28% versus 27%, p=0.37), while a lower CI of chronic GVHD (cGVHD) (27% versus 42%, p<0.01) and extensive cGVHD (12% and 19%, p<0.01) was observed in HSCT from Haplo compared to MSD, respectively. At two years, overall survival (OS) was 25% and 32% (p<0.01), leukemia-free survival (LFS) 19% and 27% (p<0.01) and GVHD/relapse-free survival (GRFS) 18% and 26% (p<0.01) in HSCT from Haplo and MSD, respectively. Relapse incidence (RI) was similar following HSCT from Haplo and MSD (50% vs 51%, p=0.60), while non-relapse mortality (NRM) was higher for Haplo transplants (31% vs 22% in HSCT from MSD, p<0.001), respectively. In a multivariate analysis adjusted for the differences between the two groups, Haplo HSCT was associated with lower OS (HR 1.19, p<0.04), LFS (HR 1.17, p<0.05) and GRFS (HR 1.22, p<0.02). Higher grade II-IV aGVHD was observed in Haplo recipients. Neither cGVHD (any grade) nor RI differed according to donor type (p=ns). Compared to MSD, Haplo recipients experienced a higher NRM (HR 1.4, p<0.02) mainly related to a higher incidence of infections (41% versus 25%, p<0.01). Regardless of donor type, age as a continuous variable was associated with lower RI (HR 0.99, p<0.01), lower OS (HR 1.01, p<0.01) and higher NRM (HR 1.02, p<0.01). The use of peripheral blood as stem cell source was independently associated with a higher risk of cGVHD (HR 1.64, p<0.01).Conclusions: Our results indicate that for pts with R/R-AML outcome is better with HSCT from a MSD compared to unmanipulated Haplo donor, mainly due to the higher NRM associated with transplants from Haplo and most probably related to a higher incidence of infections and grade II-IV aGVHD. Chronic GVHD as well as RI are similar, indicating once again that despite the broader HLA disparities with Haplo HSCT the graft versus leukemia effect is probably not stronger than after HSCT from MSD (Ringden O, on behalf of the ALWP; Leukemia 2016). In the absence of a MSD, Haplo HSCT may represent a valid alternative, with nearly one quarter of the R/R-AML pts surviving at 2 years from transplant. Future goals in the Haplo setting should be to reduce NRM and rate of infections in order to further improve outcomes. DisclosuresCiceri:GSK: Other: B-thalassemia gene therapy was developed by Fondazione Telethon and Ospedale San Raffaele and has been inlicenced by GSK that provides funding for the clinical trial, Research Funding. Mohty:Sanofi: Honoraria, Speakers Bureau.

IDH1R132, IDH2R140 and IDH2R172 in AML: Different Genetic Landscapes Correlate with Outcome and May Influence Targeted Treatment Strategies

Introduction: In AML, IDH mutations can be found at a frequency of 7% for IDH1 and 10% for IDH2 . Precision medicine aims at specifically targeting different gene mutations. Novel drugs which inhibit mutated IDH activity, such as AG-120 (for IDH1), AG-221 (for IDH2) or AG-881 (for IDH1 and 2), are currently tested in clinical trials to assess whether they confer better prognosis and overall survival to patients that carry these mutations.Aim: To comprehensively investigate the genetics and prognosis of de novo AML with IDH1 R132, IDH2 R140, and IDH2 R172 mutations.Patients and Methods: In a cohort of 306 de novo AML patients (pts) - all IDH1 or IDH2 mutated - cytomorphology and cytogenetics were available. The cohort comprised 141 females and 165 males, the median age was 65 yrs (range: 21-90 yrs). In all pts a 25-gene panel was investigated by next generation sequencing: ASXL1, BCOR, CALR, CBL, CEBPA, CSNK1A1, DNMT3A, ETV6, FLT3, IDH1, IDH2, JAK2, KIT, KRAS, MPL, NPM1, NRAS, RUNX1, SETBP1, SF3B1, SRSF2, TET2, TP53, U2AF1, and ZRSR2 . FLT3 -ITD and KMT2A -PTD were analyzed by gene scan. All pts were treated with intensive standard chemotherapy. Overall survival (OS) analyses were performed in comparison to a FAB and MRC (Grimwade et al., Blood 2010;116(3):354-365) matched IDH wild type (wt) reference cohort (n=540).Results: In total,106 pts (35%) were mutated in IDH1 R132, 166 (54%) in IDH2 R140 and 34 (11%) in IDH2 R172. Regarding amino acidic substitutions, IDH1 R132 was dominated by the R132H substitution in 44 (41%) and the R132C in 39 cases (37%); IDH2 R140 was largely skewed towards the R140Q substitution which occurred in 92% of cases; IDH2 R172 showed R172K in 32 cases (94%) and R172W in 2 cases (6%).The majority of pts had mutations in two (n=148, 44%) or three (n=78, 23%) of the other 24 analyzed genes (range: 0-6), while only six pts (2%) showed no additional mutations. Among FAB classification, 144 pts (47%) were classified as M1 and 94 (31%) as M2; this rather immature phenotype was most prominent in IDH1 mutated pts with an even higher percentage of M1 (64%) and less of M2 (22%). AML M3 was not present in this cohort at all, indicating a specific occurrence of IDH mutations in distinct AML types. Cytogenetic analyses revealed that 227 pts (74%) had a normal karyotype, 79 (26%) showed an aberrant karyotype with only 6 pts (2%) having a complex karyotype. This is also reflected by a high number of pts in the intermediate MRC group (n=285), while only 6 and 15 pts were grouped to the favorable MRC or adverse MRC group, respectively.Most frequently IDH mutated pts were also mutated in NPM1 (49%), followed by DNMT3A (40%), SRSF2 (29%), FLT3 -ITD (21%), ASXL1 (16%), NRAS (15%), RUNX1 (15%), and KMT2A -PTD(13%). All other analyzed genes were mutated in <10% of cases. Of note, no IDH2 R172 mutated patient carried a NPM1 mutation, but 63% and 50% of pts mutated in IDH1 R132 and IDH2 R140 (p<0.001). This was also true for NRAS with 18% and 17% of pts mutated in IDH1 R132 and IDH2 R140 (p=0.001). FLT3 was mutated rarely in patients with IDH2 R172 (5%) compared to those with mutations in IDH1 R132 (28%) or IDH2 R140 (32%; p=0.001). In contrast BCOR was often mutated in IDH2 R172 mutated pts (32%) compared to 5% and 7% of pts mutated in IDH1 R132 and IDH2 R140 (p<0.001). SRSF2 was frequently mutated in IDH2 R140 mutated pts (43%; p<0.001) compared to pts mutated in IDH1 R132 (13%) and IDH2 R172 (8%). ASXL1 mutations were rare in IDH1 R132 mutated pts (8%; p=0.007) compared to 22% and 16% in IDH2 R140 and R172 mutated pts.Overall survival analysis did not show significant differences between IDH1 and IDH2 mutated and IDH wt pts. However, when separating IDH1 R132, IDH2 R140, and IDH2 R172 mutated pts, the latter group showed a better prognosis (median OS not reached) compared to all others (median OS: 28 months; p=0.040; Fig. 1). Other worse prognostic factors in IDH mutated pts were higher white blood cell count (WBC) and age, or ASXL1, DNMT3A, SRSF2, and TP53 mutations. NPM1 mutations showed a favorable impact. In multivariate analyses, only IDH R172 mutation, WBC, and age remained independent prognostic factors.Conclusions: AML pts with IDH1 R132, IDH2 R140, and IDH2 R172 mutations differ in their morphological and genetic patterns. This translates into a more favorable outcome for IDH2 R172 mutated pts. Therefore, IDH mutated AML need further molecular subclassification to define prognosis and select optimal targeted treatment strategies accordingly. [Display omitted] DisclosuresMeggendorfer:MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

Salvage therapies in transplant-eligible relapsed classic Hodgkin lymphoma, are novel regimens better?

7530 Background: Clinical trials of novel salvage therapies (ST) have encouraging outcomes for relapsed/refractory classic Hodgkin lymphoma (R/R cHL) eligible for autologous stem cell transplant (ASCT). In this observational study, we report efficacies and outcomes of different ST in ASCT-eligible R/R cHL. Methods: Consecutive ASCT-eligible R/R cHL pts at 3 Mayo Clinic sites were included. Demographics and clinical variables at relapse were recorded by medical records review. Time to event endpoints were defined from relapse. Univariate associations were confirmed in multivariate models of age, sex, B symptoms, stage, bulky disease (BD, single mass &gt; 6 cm) extra nodal disease (END), primary refractory disease (PRD) and early relapse (ER, within 1 year). Results: From Jan 2008 to May 2020, 207 ASCT-eligible pts with R/R cHL were included. Median age was 33 (24-43) years, 53% were male, 52% had advanced stage, 24% had BD, 36% had B symptoms, 41% had END, 11% had PRD and 43% had ER. All patients received ST and underwent ASCT; 43 (21%) received 2 ST, 14 (7%) 3 ST and 4 (0.5%) received 4 ST. 6 groups of ST were identified: ifosfamide, carboplatin and etoposide (ICE), bendamustine/brentuximab (BBV), brentuximab vedotin (BV), gemcitabine-based therapy (Gem), checkpoint inhibitor (CPI), and others. Table lists response to first line ST. BBV had significantly higher overall response rate (ORR) and complete response (CR) as first ST in univariate and multivariate models. 114 (79%) after ICE, 30 (97%) after BBV, 15 (56%) after BV, 25 (76%) after Gem, 8 (73%) after CPI and 15 (79%) after other ST underwent ASCT. Higher number of pts were bridged to ASCT after BBV than ICE (p&lt;0.01). 110 (53%) went to ASCT in CR, 74 (36%) in partial response (PR) and 11% in progressive disease (PD). 43 received BV maintenance (BVm) after ASCT. Pts going to ASCT in PR or PD had significantly lower progression free survival (PFS) compared to pts in CR (2 yr PFS: 62%, 18% vs 77%, respectively, p&lt;0.0001) in univariate and multivariate models. There was no difference in PFS and overall survival (OS) by type of ST. BVm was associated with higher PFS (HR 0.3 (CI95 0.2-0.8)) and higher number of ST was associated with lower OS (HR 2 (CI95 1.4-3)) in multivariate model (p&lt;0.001). For pts transplanted in CR, there was no significant difference in PFS and OS by type of ST but higher number of ST predicted lower OS (HR 2.4 (CI95 1.2-3.5), p&lt;0.01). Conclusions: Type of ST did not predict survival, response to and number of ST did. For pts with CR, number of ST not type of ST predicted survival. BBV had higher response rates, higher rates of bridge to ASCT, and may be a preferable ST than ICE. Large, randomized trials are needed to evaluate efficacy of BBV compared to ICE.[Table: see text]

Real World Outcomes of Adult B-Cell Acute Lymphocytic Leukemia Patients Treated with Blinatumomab

Real World Outcomes of Adult B-Cell Acute Lymphocytic Leukemia Patients Treated with Blinatumomab

Efficacy and Safety of Venetoclax (Ven) + Rituximab (R) or Ven + Bendamustine (B) + R Randomized Versus B + R in Patients (pts) with Relapsed/Refractory (R/R) Follicular Lymphoma (FL): Final Analysis of Phase II CONTRALTO Study

Efficacy and Safety of Venetoclax (Ven) + Rituximab (R) or Ven + Bendamustine (B) + R Randomized Versus B + R in Patients (pts) with Relapsed/Refractory (R/R) Follicular Lymphoma (FL): Final Analysis of Phase II CONTRALTO Study

Epidemiology of Extranodal Diffuse Large B Cell Lymphomas in Algeria: A Study of the Algerian Group of Extranodal Lymphomas (GALEG)

Introduction: Primitive extranodal lymphomas are a heterogeneous group of malignant lymphoid hematological developed from the mucosa-associated lymphoid tissue (MATL) or sites that have acquired MALT after repeated stimulation. The particularity of this type of affection reside: the access to diagnosis which is difficult and therapeutic approach which respond to the ATB, antiviral, surgery and RT. They represent 24-48% of lymph node lymphomas and they are increasing. The incidence of lymphoma is growing in the world, it is approximately 16.8 / 105inhabitants. In Algeria in 2012, the incidence of lymph node lymphomas in adults was 2.24 / 100,000. Lymphomas Diffuse large B-cell phenotype (DLBCL) represent 50-60% of lymphomas, it is the most common histological type.Goals of the study:1-analyze the epidemiological characteristics (gender, age, geographical distribution, annual incidence). 2- Identify anatomical sites. 3- Specify the clinical and prognostic featuresPatients and methods: It's is a multicenter, retrospective study over a period between 2010-2014. The study population included all pts over 15 years and having an extranodal DLBCL at 18 hematology centers and 4 cancer centers. Data were collected on data sheets distributed to the various services involved in the study. The diagnosis is made on the histological examination of a biopsy of the affected organ. The clinical, biological and imaging results allowed us to classify and identify prognostic factors for pts.Results: Among 1057 sheets of extranodal lymphomas, the type DLBCL is specified in 562 (53%) cases, distributed in 325 men and 237 women (sex ratio M/F: 1.36). The average age at diagnosis is 51 years (16-88) with a peak in the age group 50-60 years. The overall annual incidence of 0.31/105 inhabitants/year and the specific incidence for patients over 15 years is 0.42 / 105inhabitants/year. PS 0-1: 323 / 543pts (60%). Number of pts (pts) by place of care: Annaba 65, Sétif: 60, CAC Constantine: 53, Tizi Ouzou: 49, Blida Cac: 41, CMPC-hematology: 40, Tlemcen: 30, Beni- Méssous- hematology: 29, CAC CPMC: 24, EHUOran: 23, hematology CAC Batna: 22, CHU Oran: 19, HMRUO: 17, Blida-hematology: 16, HCA:16, SBA: 15, CAC Béni-Messous: 14, EPH Mascara: 10, HMRU Oran: 9, Bejaia: 7, hematology CHU Batna: 2, hematology Cne:1. Number of cases according to anatomical localisation: Stomach: 180, Intestine: 31, Colon 12, Tonsils: 70, Cavum: 31, nasal cavities: 11, Bones: 43, mediastinum: 41, SNC: 29, Skin: 25, Rate / MO :15, Thyroid: 12, soft Parties: 10, Breast: 6, lung / pleural: 5, Liver: 5, Others: 36. The clinical symptomatology is very heterogeneous, specifically of the affected organ. Clinical stage is specified in 549 cases, according to Ann Arbor: SCIE: 272 (49%), SCIIE: 149 (27%), SCIIIE: 31 (6%), SCIV: 97 (18%). The International Prognostic Index adjusted for age (IPIaa) include: for pts less than 60 years: Low (F): 70 (23%), lower intermediate (IF): 130 (43%), intermediate high (IE) : 69 (23%), high (H): 32 (11%); for over 60 years Topics: F: 33 (23%), MI: 53 (37%) IE: 41 (28%), E: 17 (12%).Comments: As with other types of lymphoma, there is a male predominance and a peak incidence in the age group 50-60 years. The higher number of pts in the center and east of the country is probably related to a denser population in these regions. The histological type DLBCL at 53% is in agreement whith what it is conventionally reported. The incidence of 0.31/105inhabitants/year extranodal DLBCL is lower than the overall nodal DLBCL, however, the incidence of extranodal NHL is rarely determined. The number of cases of extranodal lymphomas described in this study is certainly below the actual number because this group of disorders is supported by various specialties related to the location of lymphoma. Extranodal lymphomas has a clinical polymorphism, but it is recognized that gastric and tonsillar locations are the most common, the other despite their rarity, require attention from management. This type of lymphoma is characterized by a preponderance of localized stages unlike ganglion lymphomas where the extended stages predominate. Likewise distribution by IPIaa not exceeding one pejorative factor is more common.Conclusion: Extranodal DLBCL are rare, they are characterized by a diversity clinicopathological that challenges us to homogenization of their treatment in multidisciplinary level. DisclosuresNo relevant conflicts of interest to declare.

Adverse effect profile of patients receiving anti viral treatment for chronic Hepatitis C virus infection

Chronic hepatitis C virus infection is present in 3 - 10 % of Pakistani population and genotype 3 is the most prevalent subtype in our patients. In a suitable candidate interferon along with Ribavirin is the main stay of treatment for these patients. These drugs have short as well as long term safety problem. Morbidity and frequency of discontinuation of therapy correlate directly with the frequency of adverse events while on treatment. Objectives: This observational study has been conducted to find out the adverse effect profile of anti viral treatment for our Chronic HCV patients. Material and method: From 1st March 2005 to 30th March 2005, 100 consecutive patients suffering from chronic HCV infection receiving standard interferon alpha 2 b and ribavirin were included. All of them were inquired on a questionnaire about the adverse events and then analyzed. Results and discussion: In as many as 65 % of the patients receiving anti viral treatment complained of an adverse event. The events were in the form of Flu like symptoms, abdominal pain, sleep disturbance, lack of appetite, dry cough and breathlessness, Depression, persistent fever, anemia, thrombocytopenia, neutropenia and skin rash. Conclusion: A high number of pts receiving anti viral treatment for ch. HCV infection suffer from adverse events.