SURG-13. Multiplicity does not affect outcomes in patients with surgically treated brain metastases

Abstract Background Having multiple brain lesions has been considered a negative prognostic factor in patients with brain metastases. The role of surgery in the management of these patients remains a matter of debate. Methods We retrospectively reviewed our patients who underwent surgical resection of brain metastases from January 2018 to December 2019, and examined outcomes including overall survival (OS), progression free survival (PFS) and rates of local failure. Results We identified 130 patients who underwent surgical resection as the primary treatment modality of brain metastases. At the time of surgery, 117 patients harbored 1–3 lesions, 13 had more than 3 lesions. Overall survival at two years for our entire cohort was 46%. The difference in OS between patients with > 3 metastases (21%) and 1–3 metastases (49%) was not statistically significant (HR=1.34, 95% CI: 0.67–2.68, p=0.41). Similarly, 27% of patients had PFS at two years, with 25% in the multiple metastases group and 28% in the comparison group (HR=1.19, 95% CI: 0.63–2.23, p=0.59). Additionally, 32% of patients overall experienced local failure at two years and there was no significant difference between patients with >3 metastases (15%) and those with fewer (33%) (HR=0.68, 95% CI: 0.21–2.19, p=0.52). A multivariate regression model examining multiple preoperative features revealed large tumor volume to be the only independent predictor of limited OS (p = 0.017) and PFS (p = 0.023), and local failure (p = 0.031). Conclusions In carefully selected patients, surgical resection is a reasonable management option for patients with multiple brain metastases.

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RTHP-33. A SINGLE INSTITUTION RETROSPECTIVE ANALYSIS ON SURVIVAL BASED ON TREATMENT PARADIGMS FOR PATIENTS WITH ANAPLASTIC OLIGODENDROGLIOMA

Neuro-Oncology ◽

10.1093/neuonc/noz175.904 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi216-vi217

Author(s):

Jacob Young ◽

Yalan Zhang ◽

Annette Molinaro ◽

Jennie Taylor ◽

Jennifer Clarke ◽

...

Keyword(s):

Overall Survival ◽

Surgical Resection ◽

Univariate Analysis ◽

Anaplastic Oligodendroglioma ◽

Radiation Toxicity ◽

Single Institution ◽

Current Standard ◽

Entire Cohort ◽

Significant Difference

Abstract Anaplastic oligodendrogliomas are a type of high grade glioma defined molecularly by the 1p19q co-deletion. Currently, there is no curative therapy, and some studies have estimated median survival is estimated to be approximately 5 years. Current standard of care includes surgical resection followed by radiation and chemotherapy. However, the benefit of up-front radiation with chemotherapy compared to chemotherapy alone following surgical resection has not been shown in a randomized control trial. Given the long-term cognitive consequences of radiation therapy and the high percentage of patients who lives beyond 15 years with AO, there is an effort to balance longevity with radiation toxicity. As such we performed a retrospective single institution analysis of survival of patients with anaplastic oligodendroglioma over 20 years. 159 patients were identified as diagnosed with an anaplastic oligodendroglioma between 1996–2016. Of those, 57 patients were found to have anaplastic olidodendroglioma at original diagnosis and had long term follow-up. Sixty-six percent of patients were between the ages of 30–50 and mean KPS was 87.3. At the time of analysis, 33% of patients had died. In this cohort, 60% of patients were initially treated with radiation and chemotherapy (either temozolomide or CCNU) at diagnosis and 40% were treated with chemotherapy alone. Median overall survival for the entire cohort was 142 months. The related risk of progression in the upfront chemotherapy only group is approximately 5.87 times higher than the patients who received radiation and chemotherapy (Hazard ratio=5.87, 1.92–17.90, p=0.002). However, there was no significant difference in overall survival in patients treated with upfront chemotherapy compared to patients treated upfront with chemotherapy and radiation (p=0.14). On univariate analysis, there was no association between age, KPS, EOR, or upfront vs. delayed radiation and survival. As such initial treatment with chemotherapy alone may be an option for some patients with anaplastic oligodendroglioma.

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Upfront Brain Radiotherapy Improves Intracranial Progression-Free Survival but not Overall Survival in Lung Adenocarcinoma Patients with Brain Metastases: A Retrospective Single-Institutional Analysis from China

10.21203/rs.3.rs-40353/v1 ◽

2020 ◽

Author(s):

Aijun Jiang ◽

Meng Ni ◽

Li Li ◽

Fen Zhao ◽

Yuanhu Yao ◽

...

Keyword(s):

Overall Survival ◽

Brain Metastases ◽

Lung Adenocarcinoma ◽

Gene Mutation ◽

Therapeutic Option ◽

Progression Free Survival ◽

Free Survival ◽

Entire Cohort ◽

Brain Radiotherapy ◽

Subgroup Analyses

Abstract Aims: There is no consensus on the optimal opportunity of brain radiotherapy (BRT) for the patients with lung adenocarcinoma and brain metastases (BM). In the present study, we performed a retrospective review to investigate the differential benefit of upfront BRT for lung adenocarcinoma patients with BM.Methods: A total of 354 lung adenocarcinoma patients with BM from the Affiliated Cancer Hospital of Shandong University met inclusion criteria for the study. Patients were divided into two groups: upfront BRT and deferred BRT. Intracranial progression-free survival (iPFS) and Overall survival (OS) were measured from the date of brain metastases. Subgroup analyses according to gene mutation status were also performed.Results: For the entire cohort, the median iPFS of upfront BRT and deferred BRT was 16.3 and11.3 months, respectively (p =.001). The median OS of upfront BRT and deferred BRT was 27.6 and 31.5 months, respectively (p =0.813). Subgroup Analyses indicated that upfront BRT yielded a significantly longer iPFS than deferred BRT (p = 0.003) only for patients with no sensitive gene mutation. In all subgroups, the median OS was not significant different for upfront BRT and deferred BRT.Conclusion: This single-institutional retrospective showed that in patients with lung adenocarcinoma and BM, upfront BRT was associated with significantly longer iPFS, but no OS difference between upfront BRT and deferred BRT was observed. Considering the reported neurocognitive toxicities of upfront BRT, deferred BRT might be considered as an acceptable therapeutic option for the treatment of patients with lung adenocarcinoma and BM.

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Upfront brain radiotherapy improves intracranial progression-free survival but not overall survival in lung adenocarcinoma patients with brain metastases: a retrospective, single-institutional analysis from China

10.21203/rs.3.rs-40353/v2 ◽

2020 ◽

Author(s):

Aijun Jiang ◽

Meng Ni ◽

Li Li ◽

Fen Zhao ◽

Yuanhu Yao ◽

...

Keyword(s):

Overall Survival ◽

Retrospective Study ◽

Brain Metastases ◽

Lung Adenocarcinoma ◽

Gene Mutation ◽

Progression Free Survival ◽

Free Survival ◽

Brain Radiotherapy ◽

Significant Difference ◽

Subgroup Analyses

Abstract Aims: The optimal timing of brain radiotherapy (BRT) for lung adenocarcinoma patients with brain metastases (BM) remains controversial. In this retrospective study, we performed a retrospective review to investigate the differential benefit of upfront versus deferred BRT for lung adenocarcinoma patients with BM.Methods: A total of 354 lung adenocarcinoma patients with BM treated in the Affiliated Cancer Hospital of Shandong University met the inclusion criteria for the study. Patients were divided into two groups: upfront BRT and deferred BRT. Intracranial progression-free survival (iPFS) and overall survival (OS) were measured from the date of brain metastases. Subgroup analyses according to gene mutation status were also performed.Results: Among the entire cohort, the median iPFS with upfront BRT (16.3 months) was longer than that with deferred BRT (11.3 months, p=0.001). However, the median OS did not differ significantly between patients who received upfront BRT and deferred BRT (27.6 and 31.5 months, respectively, p=0.813). Subgroup analyses indicated that upfront BRT yielded a significantly longer iPFS than deferred BRT (p=0.003) only for patients without EGFR gene mutation. In all subgroups, the median OS showed no significant difference between upfront BRT and deferred BRT.Conclusion: This single-institutional retrospective study showed that in patients with lung adenocarcinoma and BM, upfront BRT was associated with a significantly longer iPFS but no improvement in OS compared with deferred BRT. Considering the neurocognitive toxicities of BRT previously reported in the literature, deferred BRT might be considered as an acceptable therapeutic option for the treatment of patients with lung adenocarcinoma and BM.

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Serum HE4 as a prognostic marker in cervical cancer: a retrospective study

10.21203/rs.3.rs-75394/v1 ◽

2020 ◽

Author(s):

Woo Yeon Hwang ◽

Dong Hoon Suh ◽

Kidong Kim ◽

Yong Beom Kim ◽

Jae Hong No

Keyword(s):

Cervical Cancer ◽

Overall Survival ◽

Tumor Marker ◽

Progression Free Survival ◽

Patient Characteristics ◽

Figo Stage ◽

Primary Treatment ◽

Positive Lymph Node ◽

Large Tumor ◽

Free Survival

Abstract Background Human epididymis protein 4 (HE4) is a tumor marker that has been well-investigated in ovarian and endometrial cancers. The aim of this study was to evaluate the prognostic value of serum HE4 as a tumor marker in patients with cervical cancer. Methods Serum HE4 levels from 67 cervical cancer patients were measured by immunoassay before starting primary treatment between September 2014 and May 2018. A mean serum HE4 level of 72.6 pmol/L was used to divide the patients into low and high HE4 groups. The patient characteristics, clinicopathological variables, and survival outcomes were compared between the 2 groups. Results There were 55 (82.1%) patients in the HE4 < 72.6 pmol/L group and 12 (17.9%) patients in the HE4 > 72.6 pmol/L group at the date of diagnosis. Higher HE4 levels were significantly associated with older age at diagnosis (age < 50: 0.0% vs. age ≥ 50: 100.0%; P = 0.002), menopause (premenopause: 8.3% vs. postmenopause: 91.7%; P = 0.009), higher FIGO stage (stage I-II: 25.0% vs. III-IV: 75.5%; P = 0.008), large tumor size (< 4.0cm: 41.7% vs. ≥4.0 cm: 58.3%; P = 0.029), positive lymph node metastasis (negative: 41.7% vs. positive: 58.3%; P = 0.049), and involvement of the parametrium (negative: 25.0% vs. positive: 75.0%; P = 0.006). Higher levels of HE4 was a predictive factor for worse overall survival but not for progression-free survival, although elevated HE4 levels were not found to be independent factors for the prediction of either overall survival or progression-free survival. When subgroup analysis was performed by histological type, similar results were obtained for patients with squamous cell carcinoma. Conclusions Our data revealed that high levels of HE4 expression were correlated with poor OS, indicating that elevated HE4 levels are associated with a poor prognosis for patients with cervical cancer.

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LINAC-based stereotactic radiosurgery/radiotherapy for brain metastases in patients with breast cancer

Journal of Radiotherapy in Practice ◽

10.1017/s1460396921000029 ◽

2021 ◽

pp. 1-9

Author(s):

Ankita Gupta ◽

Budhi Singh Yadav ◽

Nagarjun Ballari ◽

Namrata Das ◽

Ngangom Robert

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Progression Free Survival ◽

Rank Test ◽

Karnofsky Performance Score ◽

Breast Cancer Patients ◽

Free Survival ◽

Prior Surgery

Abstract Background: Brain metastases (BM) are common in patients with HER2-positive and triple-negative breast cancer. In this study we aim to report clinical outcomes with LINAC-based stereotactic radiosurgery/radiotherapy (SRS/SRT) for BM in patients of breast cancer. Methods: Clinical and dosimetric records of breast cancer patients treated for BM at our institute between May, 2015 and December, 2019 were retrospectively reviewed. Patients of previously treated or newly diagnosed breast cancer with at least a radiological diagnosis of BM; 1–4 in number, ≤3·5 cm in maximum dimension, with a Karnofsky Performance Score of ≥60 were taken up for treatment with SRS. SRT was generally considered if a tumour was >3·5 cm in diameter, near a critical or eloquent structure, or if the proximity of moderately sized tumours would lead to dose bridging in a single-fraction SRS plan. The median prescribed SRS dose was 15 Gy (range 7–24 Gy) and SRT dose was 27 Gy in 3 fractions. Clinical assessment and MR imaging was done at 6 weeks post-SRS and then every 3 months thereafter. Intracranial progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method and subgroups were compared using log rank test. Results: Total, 40 tumours were treated in 31 patients. The median tumour diameter was 2·3 cm (range 1·0–4·6 cm). SRS and SRT were delivered in 27 and 4 patients, respectively. SRS/SRT was given as a boost to whole brain radiotherapy (WBRT) in four patients and as salvage for progression after WBRT in six patients. In general, nine patients underwent prior surgery. The median follow-up was 7·9 months (0·2–34 months). Twenty (64·5%) patients developed local recurrence, 10 (32·3%) patients developed distant intracranial relapse and 7 patients had both local and distant intracranial relapse. The estimated local control at 6 months and 1 year was 48 and 35%, respectively. Median intracranial progression free survival (PFS) was 3·73 months (range 0·2–25 months). Median intracranial PFS was 3·02 months in patients who received SRS alone or as boost after WBRT, while it was 4·27 months in those who received SRS as salvage after WBRT (p = 0·793). No difference in intracranial PFS was observed with or without prior surgery (p = 0·410). Median overall survival (OS) was 21·7 months (range 0·2–34 months) for the entire cohort. Patients who received prior WBRT had a poor OS (13·31 months) as compared to SRS alone (21·4 months; p = 0·699). Conclusion: In patients with BM after breast cancer SRS alone, WBRT + SRS and surgery + SRS had comparable PFS and OS.

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IMMU-08. MODELING UPFRONT GLIOBLASTOMA SURGICAL RESECTION AND STEROID USE REVEALS IMMUNOSUPPRESSIVE CHANGES AND SUGGESTS THAT PERIPHERAL LYMPHOCYTE COUNTS ARE ASSOCIATED WITH TUMOR VOLUME AND PROGNOSIS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.439 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii106-ii106

Author(s):

Balint Otvos ◽

Tyler Alban ◽

Matthew Grabowski ◽

Defne Bayik ◽

Robert Winkelman ◽

...

Keyword(s):

Bone Marrow ◽

Overall Survival ◽

Surgical Resection ◽

Cd8 T Cells ◽

Tumor Volume ◽

Progression Free Survival ◽

Peripheral Lymphocyte ◽

Steroid Use ◽

Free Survival ◽

Steroid Administration

Abstract Glioblastoma (GBM) and its treatment produces systemic immunosuppression, which is being targeted by immunotherapies. However, it remains unclear how surgical resection and steroids specifically in GBM alter the immune system. To further explore this issue, immunocompetent C57Bl/6 mice were intracranially inoculated with syngeneic glioma cells (GL261 and CT-2A) and growth of tumors was evaluated by MRI. Host immune cell populations were analyzed during surgical resection and steroid administration. Mice with surgically resected tumors had a longer median survival compared to mice subjected to tumor biopsies, and had increased bone marrow sequestration of both CD4 and CD8 T cells with corresponding decreased blood lymphocytes. Furthermore, physiologic doses of dexamethasone administered perioperatively decreased tumor edema, but increased the number and proliferative capacity of both marrow and circulating MDSCs while generating no survival benefit. Independent of therapy or dexamethasone, intracranial tumor volume correlated linearly with decreased CD4 and CD8 T cells in peripheral blood, and increased T cell sequestration within the bone marrow. We validated these parameters in steroid-naïve newly diagnosed GBM patients and observed decreased lymphocytes correlated linearly with increased tumor volume. When initial lymphocyte counts in both steroid-naïve and steroid-administered patients were used in univariate and multivariate models predicting progression-free survival and overall survival, decreased initial lymphocyte counts were an independent predictor of decreased progression free survival and decreased overall survival, with steroid use and initial tumor size falling out of significance during stepwise selection. Taken together, tumor volume is linearly correlated with marrow sequestration of lymphoid cells, but both surgery and steroid administration further suppress active immune responses along lymphoid and myeloid lineages. Furthermore, decreasing peripheral lymphocyte counts at diagnosis of GBM indicate an immune system less able to mount responses to the tumor and portent a worse progression free and overall survival.

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Evaluation of efficacy and toxicity of nivolumab combined with or without docetaxel in patients with advanced NSCLC

Cancer Immunology Immunotherapy ◽

10.1007/s00262-021-02964-x ◽

2021 ◽

Author(s):

Yang Wang ◽

Jun Nie ◽

Ling Dai ◽

Weiheng Hu ◽

Jie Zhang ◽

...

Keyword(s):

Overall Survival ◽

Advanced Nsclc ◽

Objective Response ◽

Progression Free Survival ◽

Meaningful Improvement ◽

Free Survival ◽

Significant Difference ◽

Grade 3 ◽

Doublet Chemotherapy ◽

Platinum Doublet

Abstract Background The combination of PD-1/PD-L1 inhibitor and chemotherapy has been clinically confirmed to be beneficial as the first-line treatment of patients with advanced NSCLC. This study aimed to assess the effect of nivolumab + docetaxel versus nivolumab monotherapy in patients with NSCLC after the failure of platinum doublet chemotherapy. Materials and methods The efficacy and toxicity of nivolumab + docetaxel combination therapy versus nivolumab monotherapy were compared in this retrospective study. Primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and toxicity. Results Between November 2017 and December 2019, 77 patients were included in this study, with 58 patients in the nivolumab group and 19 in the nivolumab + docetaxel group. The median follow-up was 18 months, and the PFS was 8 months for patients receiving nivolumab + docetaxel and 2 months for those receiving nivolumab alone (p = 0.001), respectively. Nivolumab + docetaxel showed superior OS compared with nivolumab, with the median OS unreached versus 7 months (p = 0.011). Among patients without EGFR/ALK variation, compared to nivolumab monotherapy, nivolumab + docetaxel showed better PFS (p = 0.04) and OS (p = 0.05). There was no significant difference in grade 3–4 adverse events (AEs) between the two groups (p = 0.253). Conclusions The combination of nivolumab and docetaxel demonstrated a meaningful improvement in progression-free survival and overall survival compared to nivolumab monotherapy, in patients with NSCLC after the failure of platinum doublet chemotherapy, irrespective of EGFR/ALK variation status.

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Treatment outcomes of recurrent and metastatic adenoid cystic carcinoma: A retrospective analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e18056 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e18056-e18056

Author(s):

Julie Elaine McGrath ◽

Punita Grover ◽

Joanne Xiu ◽

Chadi Nabhan ◽

Jennifer Hsing Choe ◽

...

Keyword(s):

Overall Survival ◽

Adenoid Cystic Carcinoma ◽

Real World ◽

Kinase Inhibitors ◽

Checkpoint Inhibitors ◽

Predictive Biomarkers ◽

High Rate ◽

Entire Cohort ◽

Adenoid Cystic ◽

Significant Difference

e18056 Background: Adenoid cystic carcinoma (ACC) is a rare malignancy of glandular tissue with a high rate of local recurrence and metastatic disease. Despite being regarded as an indolent disease, the clinical course of recurrent and metastatic ACC (R/M ACC) is highly variable. Responses to chemotherapy (chemo) are uniformly poor. Several multi-targeted tyrosine-kinase inhibitors (mTKIs), EGFR inhibitors (EGFRi) and other targeted agents have been studied in single-arm early phase trials with response rates ranging from 0-16% and progression free survival ranging from 2.5-17 months. However, there have been no comparative clinical trials and it is not known if one treatment strategy is superior. We undertook this retrospective study to assess the real-world clinical outcomes in patients with adenoid cystic carcinoma using the Caris Life Sciences database. Methods: Real world overall survival (rwOS) for cases of ACC was obtained from insurance claims data and Kaplan-Meier estimates were calculated from the date of collection to the date of last contact. Cases were divided into subgroups based on treatment received – chemo (including platinum agents, taxanes, 5FU, topoisomerase inhibitors, anthracyclines), EGFRi (cetuximab, erlotinib, lapatinib), mTKIs (pazopanib, axitinib, sunitinib, cabozantinib, lenvatinib, sorafenib) and immune checkpoint inhibitors (ICIs) (atezolizumab, ipilimumab, pembrolizumab, nivolumab). Results: 368 patients (pts) were identified with ACC, 16 were locally recurrent and 216 tumors were taken from metastatic sites. 50 pts received chemo, 6 were treated with EGFRi and 15 with mTKIs. Pts who received combination EGFRi and chemo or mTKI and chemo were excluded. The median overall survival (mOS) all patients with metastatic ACC was 2.8 years (yrs). The mOS of pts with R/M ACC was 3 yrs for chemo, 2.9 yrs for EGFRi and 1.5 yrs for mTKIs. There was no significance in mOS between chemo vs mTKIs (HR 0.85, 95% CI 0.3 - 2, p = 0.72) and chemo vs EGFRi (HR = 0.88, 95% CI 0.3 - 2.5, p = 0.78). We further compared the outcomes of those treated with EGFRi (n = 8) with mTKIs (n = 19) in the entire cohort. For most pts, these agents were given as front line therapy. 25% (2/8) of patients had received treatment prior to EGFRi and 20% (4/9) prior to mTKIs (p = 1). There was no significant difference in mOS with HR 0.6 (95% CI 0.16 - 2.6), p = 0.6. We also compared the mOS of patients who received ICIs (n = 22) with those who did not (n = 346) but there was no significant difference (mOS 3.19 vs 3.17 yrs respectively, HR 0.87, 95% CI 0.47- 1.61, p = 0.65). Conclusions: There was no significant difference in the mOS between pts with R/M ACC who were treated with chemo, EGFRi or TKIs and in those who received ICIs compared to those who did not in our limited patient population. This highlights the need for predictive biomarkers for better patient selection with the goal of personalizing treatment strategies for this disease.

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Are Hormonal Agents Better Than Chemo İn Metastati̇c Castrati̇on Resistant Prostate Cancer?

10.21203/rs.3.rs-199255/v1 ◽

2021 ◽

Author(s):

Serkan Yıldırım ◽

Atike Pınar ERDOĞAN ◽

Cengiz Yılmaz ◽

Ferhat Ekinci ◽

Gülcan Bulut ◽

...

Keyword(s):

Overall Survival ◽

Therapy Group ◽

Hormonal Treatment ◽

Progression Free Survival ◽

Free Survival ◽

Chemotherapy Group ◽

Randomized Controlled Studies ◽

Significant Difference ◽

Hormonal Therapies ◽

Multi Center Study

Abstract İNTRODUCTİONIn this study, we aim to determine which treatment is more appropriate in castration-resistant chemotherapy-naive patients. Therefore, docetaxel and agents active in the androgen pathway (abiraterone and enzalutamide) were compared retrospectively in patients progressing on ADT.MATERİAL METHODThe study was designed as a retrospective and multi-center study. Patients from 5 centers in Turkey were included in the study. The primary endpoint of the study was ovreall survival and the secondary endpoint was progression-free survival.RESULTSMedian overall survival of the chemotherapy group was 18.66 months, it was 16.26 months in the hormonal treatment group. There was no statistically significant difference between the groups (p = 0.311). Median progression-free survival of the chemotherapy group was 5.6 months, while it was 9 months in the hormonal therapy group. There was statistically significant difference between the groups (p = 0.024).CONCLUSİONThere was statistical difference in progression-free survival in favor of hormonal therapies in our study. The difference did not reflect on overall survival and there was no difference between hormonal therapies and docetaxel. Heterogeneity in the selection of patients is considered to lead to this result; however, larger randomized controlled studies are needed to determine the most appropriate treatment in these patients.

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Outcomes in AML patients receiving HMA + venetoclax combination with prior HMA exposure.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e19011 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e19011-e19011

Author(s):

Bakos Keegan Jonathan ◽

Dena Blanding ◽

Christopher Andrew Rangel ◽

Sarah Pasyar ◽

Elizabeth Goodwin Hill ◽

...

Keyword(s):

Overall Survival ◽

Tp53 Mutation ◽

Clinical Laboratory ◽

Retrospective Chart Review ◽

Progression Free Survival ◽

Poor Response ◽

Patient Characteristics ◽

Entire Cohort ◽

Kaplan Meier ◽

Poor Outcomes

e19011 Background: Venetoclax (Ven) is a BCL-2 inhibitor approved in combination with hypomethylating agents (HMAs) in newly diagnosed AML patients who are not candidates for intensive induction based on impressive response rates (CR+CRi of 66.4%) and median overall survival (14.7 months) compared to HMA therapy alone (DiNardo CD, NEJM, 2020). Ven was also used in combination with 10 days of a HMA (Decitabine) in a phase II study. In the subgroup of patients with relapsed AML, some of which previously received HMA, the ORR, CR+CRi, and median OS were 62%, 42%, and 7.8 months respectively. (DiNardo CD, Lancet, 2020). To our knowledge there are no studies specifically looking at patients with AML receiving HMA + Ven with previous exposure to a HMA agent. Methods: We conducted a single center retrospective study of AML patients who received HMA + Ven therapy after previously receiving a HMA agent. Baseline demographic, clinical, laboratory, pathology, and outcomes data were collected by retrospective chart review. Response criteria was determined by 2017 ELN recommendations. Kaplan Meier was constructed to summarize time to event data. Results: A total of 17 patients were identified that met these criteria. 7 patients (41%) had progressed on prior HMA treatment, 11 patients (65%) received prior intensive chemotherapy, and 5 patients (29%) received previous Allogenic SCT prior to HMA+Ven therapy. 10 patients (59%) had either a TP53 mutation or 17p deletion and 11 patients (65%) had complex cytogenetics (≥ 3 cytogenetic abnormalities). Other patient characteristics are included in table below. For the entire cohort, the ORR (CR, CRi, PR) was 41% and the CR/CRi rate was 6%; The ORR in the following subgroups for previous HMA failure, TP53 mutation/17p deletion, and complex cytogenetics were 14%, 30%, and 36% respectively. The median Progression free survival and overall survival for the entire cohort was 2 months (1-4 months 95% CI) and 3 months (1-5 months, 95% CI) respectively. 15 patients (88%) were deceased and all deaths were attributed to AML (12/15) or infection (3/15). None of the patients went on to receive an Allogenic SCT. Conclusions: Although a limited sample size which includes many patients with a TP53/17p aberration, complex cytogenetics, Allogenic SCT relapse, and/or heavily pre-treated AML, this data describes poor outcomes in patients receiving HMA+Ven after previous HMA exposure. Patients with previous HMA failure in particular had a poor response rate. None of the patients received 10 day decitabine and it is unclear if this had any effect on the results. It would be beneficial to supplement this data with experience from multiple centers. Patient Characteristics (N = 17).[Table: see text]

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