MD Anderson Experience Research Articles

Safety and Efficacy Outcomes for Patients with High-Risk Multiple Myeloma Receiving Idecabtagene Vicleucel: The MD Anderson Experience

Background: There is a paucity of data regarding the impact of high-risk features on the efficacy and safety of B-cell maturation antigen (BCMA)-directed autologous chimeric antigen receptor (CAR)-T therapy in patients with multiple myeloma (MM). Methods: In this retrospective single-center study we included all MM patients who received idecabtagene vicleucel (ide-cel) between 12/2019-10/2022, either in the setting of a clinical trial (i.e. KarMMa-2 and KarMMa-3) or as a standard of care (SOC). We evaluated the impact of high-risk disease features on the efficacy and safety outcomes. Patients with high-risk MM (HRMM) were defined as having at least one of the following: high-risk cytogenetic abnormalities prior to CAR-T infusion (deletion 17p, translocation (t)(4:14), t(14:16) or 1q gain/amplification (1q+)), extramedullary disease (EMD), plasma cell leukemia and Revised International Staging System (R-ISS) stage 3. Minimal residual disease (MRD) was evaluated using 8-color next-generation flow cytometry (NGF), with a sensitivity of 1/10-5 cells (0.001%) based on the acquisition and analysis of at least 2 million events. Efficacy outcomes included response rates, progression free survival (PFS) and overall survival (OS). Safety outcomes included incidence/grade of cytokine release syndrome (CRS), Immune effector cell-associated neurotoxicity syndrome (ICANS), hematological toxicity and infections. Results: A total of 74 patients were included in our analysis, 49 received SOC ide-cel and 25 were treated on clinical trial. The median age was 65.3 (range 37.9-90.3) years, and 49 patients (66%) were male. Median number of previous lines of therapy was 6 (range 1-18). The HRMM group included 52 patients (70%), and the most prevalent high-risk features were high-risk cytogenetic abnormalities (43%, most often 1q+ (n=26, 81%), followed by del17p (n=17, 33%), t(4:14) (n=9, 17%) and t(14:16) (n=4, 8%)) and EMD (19%). Seventy five percent of patients who received SOC ide-cel had HRMM compared to 25% of those who received ide-cel on clinical trial (p=0.014). Compared to patients with standard-risk MM (SRMM), those with HRMM more often had disease refractory to proteasome inhibitors (p=0.042) or anti-CD38 antibodies (p=0.01), and more often received bridging therapy prior to CAR-T infusion (p=0.021). After bridging therapy, 43% of HRMM patients had progressive disease, compared to 20% of SRMM patients (p=0.21). Sixty seven percent of the entire cohort received prior BCMA-directed therapy before ide-cel, without a significant difference between the two risk groups (p=0.80) ( Table 1). For the entire cohort, overall response rate was 85%, and 51% achieved ≥CR at best response. There was no significant difference between the HRMM and SRMM groups in response rates or in rates of MRD negativity at day 30 and at 3/6/9 months after CAR-T infusion, yet fewer HRMM had MRD negativity at 12 months after CAR-T (50% vs. 100% of evaluable patients, p=0.019). The 6-months PFS for the HRMM group and the SRMM group was 64% and 81%, respectively (p=0.11) ( Figure 1A), and the 6-months OS was 80% and 90%, respectively (p=0.067) ( Figure 1B); Thirty-nine patients in the HRMM group developed CRS (83% of evaluable patients), including one grade 3 and one grade 5 CRS, compared to 15 (75%, p=0.65) in the SRMM group (all grade <3). Eight patients in the HRMM group developed ICANS (17%), including two grade 4 ICANS, compared to 3 (15%, p=0.93) in the SRMM group (all grade <3). We did not observe a difference in rates of neutropenia (p=0.63), anemia (p=0.75) or thrombocytopenia (p=0.53) by day 30, and also not in the rates of infection (p=0.16) between the two groups. In multivariate analysis on the entire cohort, receiving <4 prior lines of therapy (HR 0.06, 95% CI 0.004-0.71, p=0.026) and ECOG≤2 (HR 0.07, 95% CI 0.08-0.53, p=0.01) were associated with superior OS. Conclusions: Patients with HRMM receiving ide-cel had mostly comparable response rates compared to those with SRMM. HRMM patients had numerically worse PFS and OS compared to patients with SRMM, though not reaching statistical significance. Overall rates of CRS/ICANS were comparable between the two groups, yet only patients with HRMM had grade ≥3 of these complications. Patients who received ide-cel after less than four previous lines of therapy had better overall survival.

The importance of facilitating goal-concordant care (GCC) in a pandemic: the MD Anderson Experience with hospitalized COVID-19-positive patients.

Provider-patient communication (PPC) about goals of care (GOC) facilitates goal-concordant care (GCC) delivery. Hospital resource limitations imposed during the pandemic made it vital to deliver GCC to a patient cohort with COVID-19 and cancer. We aimed to evaluate the implementation of a real-time goals of care intervention and to make recommendations for future pandemics with similar clinical scenarios. This is a retrospective cohort study, of all COVID-19 positive patients admitted to The University of Texas MD Anderson Cancer Center between March of 2020 and January of 2021. The cohort included the following: (1) patients 18 years of age or older; (2) positive COVID-19 infection; (3) requiring hospitalization. Medical records were reviewed and all patient data including demographics, comorbidities, and outcomes were collected and analyzed in the Syntropy platform, Palantir Foundry, as part of the institutional Data-Driven Determinants of COVID-19 Oncology Discovery Effort (D3CODE) protocol. A multidisciplinary GOC task force developed processes for ease of conducting GOC-PPC and implemented structured documentation. We looked at ACP documentation pre- and post-implementation alongside demographics, length of stay (LOS), 30-day readmission rate and mortality. There were 494 unique patients identified, 53% male, 61.5% Caucasian, 16.8% African American, and 3.2% Asian. Active cancer was identified in 84.6% patients, of which 65.6% were solid tumors and 34.4% hematologic malignancies. LOS was 9 days with a 30-day readmission rate of 15% and inpatient mortality of 14%. Inpatient ACP note documentation was significantly higher post-implementation as compared to pre-implementation (90% vs 8%, P<0.05). We saw sustained ACP documentation throughout the pandemic suggesting effective processes. The implementation of institutional structured processes for GOC-PPC resulted in rapid sustainable adoption of ACP documentation for COVID-19-positive cancer patients. This was highly beneficial for this population during the pandemic, as it demonstrated the role of agile processes in care delivery models, which will be beneficial in the future when rapid implementation is needed.

Single-agent lenalidomide maintenance after upfront autologous stem cell transplant for newly diagnosed multiple myeloma: The MD Anderson experience.

The optimal duration of lenalidomide (Len) maintenance for patients with multiple myeloma (MM) after autologous stem cell transplantation (autoHCT) is unknown. We conducted a retrospective single-center analysis of adult MM patients that received upfront autoHCT between 2005 and 2021, followed by single-agent Len maintenance. A total of 1167 patients were included with a median age of 61.4 (range 25.4-82.3) years, and high-risk chromosomal abnormalities in 19%. Median duration of maintenance was 22.3 (range 0.03-139.6) months. After a median follow-up of 47.9 (range 2.9-171.7) months, median PFS and OS for the entire cohort were 56.6 (95% CI 48.2-61.4) months and 111.3 (95% CI 101.7-121.5) months, respectively. In MVA, high-risk cytogenetics was associated with a worse PFS (HR 1.91) and OS (HR 1.73) (p < .001 for both). Use of KRD induction and achievement of MRD-negative ≥ VGPR before autoHCT were associated with an improved PFS (HR 0.53 and HR 0.57, respectively; p < .001 for both). Longer maintenance duration, even with a 5-year cutoff, was associated with superior PFS and OS (HR 0.17 and 0.12, respectively; p < .001 for both). A total of 106 patients (9%) developed a second primary malignancy (SPM), mostly solid tumors (39%) and myeloid malignancies (30%). Longer maintenance duration was associated with a higher risk of SPM, reaching statistical significance after >2 years (odds ratio 2.25; p < .001). In conclusion, outcomes with Len maintenance were comparable to those reported in large clinical trials. Longer duration of maintenance, even beyond 5 years, was associated with improved survival.

45. Outcomes of Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interface in Oncologic Amputees: The MD Anderson Cancer Center Experience

PURPOSE: The outcomes of targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) in oncologic amputees have been limited to small series. Herein, we report the MD Anderson experience with the surgical and postamputation outcomes of TMR and RPNI in the oncologic population. METHODS: We conducted a retrospective cohort study of consecutive patients who underwent oncologic amputation followed by TMR or RPNI from November 2018 to May 2022. Patient-reported Outcomes Measurement System (PROMIS) and Numerical Rating Scales for residual limb pain (RLP) and phantom limb pain (PLP) were obtained and compared with published benchmarked outcomes. RESULTS: We compared 68 patients with oncologic amputation at our institution with 727 patients with benchedmarked outcomes. Patients had mean follow-up period of 10.9±8.7 months. Oncologic amputees experienced significant reductions in pain intensity (-5.39; 95%CI,-4.28, -6.50; p<0.001), interference (-11.98; 95%CI, -8.19, -15.8; p<0.001), behavior (-32.95; 95%CI, -25.5,-40.4; p<0.001) and global health (-26.25; 95%CI, -22.09, -30.42; p<0.001) following TMR or RPNI from baseline to final follow-up. Delayed wound healing was the most common complication (14.7%) and tumor recurrence occurred in 36.8% of patients. Compared with benchedmarked outcomes, oncologic amputees who underwent TMR or RPNI demonstrated significantly lower median PLP (0.0 vs. 4.0, p<0.001), RLP (1.0 vs. 4, p<0.001), pain intensity (6.0 vs. 46.6, p<0.001), pain interference (9.5 vs. 55.9, p<0.001), and pain behavior (36.0 vs. 56.7, p<0.001) scores. CONCLUSION: Oncologic amputees who underwent TMR and RPNI demonstrated significant reductions in postamputation pain compared with their baseline and benchedmarked outcomes with relatively low postoperative complications rate.

Outcomes of acute lymphoblastic leukemia with KMT2A (MLL) rearrangement: the MD Anderson experience

AbstractAcute lymphoblastic leukemia (ALL) with t(4;11)(q21;q23)-KMT2A-AFF1 is associated with a poor prognosis. The impact of KMT2A rearrangements other than t(4;11) is uncertain, and the benefit of allogeneic stem cell transplantation (HSCT) is unclear. We reviewed adult patients with ALL treated at our institution from 1984 to 2019 and identified 50 out of 1102 (5%) with KMT2A rearrangement, including 42 (84%) with t(4;11)/KMT2A-AFF1 and 8 (16%) with other gene partners. The median age was 45 years (range, 18-78 years); median white blood cell count was 109.0 3 109/L (range, 0.5-1573.0). The complete remission (CR) rate was 88%, and the rate of measurable residual disease negativity by flow cytometry at CR was 41% (76% overall during follow-up). At the last follow-up, 14 patients were alive. The 5-year overall survival (OS) rate was 18% (95% confidence interval [CI], 9% to 35%), with no difference between t(4;11) and other KMT2A rearrangements (P 5 .87). In a 4-month landmark analysis, the 5-year OS rate was 32% (95% CI, 14% to 70%) in patients who underwent HSCT vs 11% (95% CI, 3-39) in others (P 5 .10). Our study confirms the poor prognosis of ALL with any KMT2A rearrangement and the role of HSCT in these patients.

History of preoperative therapy for pancreatic cancer and the MD Anderson experience.

Systemic chemotherapy improves the survival of patients who undergo pancreatectomy, but whether chemotherapy should be delivered before or after surgery remains debated. At The University of Texas MD Anderson Cancer Center, localized pancreatic ductal adenocarcinoma (PDAC) has been preferentially treated with preoperative therapy-a practice supported by a robust history of institutional and national trials. In the following review, we discuss the historical use of perioperative therapy, our experience with it at MD Anderson Cancer Center and internationally, and the future of treatment and trials for PDAC.

PO-101 Management of direct oral anticoagulant (DOAC)-related bleeding with andexanet alpha or idarucizumab versus prothrombin complex concentrate (PCC) in patients with cancer: the MD Anderson experience

PO-101 Management of direct oral anticoagulant (DOAC)-related bleeding with andexanet alpha or idarucizumab versus prothrombin complex concentrate (PCC) in patients with cancer: the MD Anderson experience

Vedolizumab for Steroid Refractory Lower Gastrointestinal Tract Graft Versus Host Disease

Vedolizumab for Steroid Refractory Lower Gastrointestinal Tract Graft Versus Host Disease

The MD Anderson experience with 3D dosimetry and an MR-linac

A recent extension of image guidance in radiation therapy has been brought about by the introduction of the MR-linac; a hybrid system comprising an MR imager and a medical linear accelerator. The University of Texas MD Anderson Cancer Center is one of seven institutes around the world that have collaborated with the manufacturer to develop this system and bring it into clinical use. In the process, a great deal has been learned about the influence of the magnetic field on radiation dose deposition and upon dosimetry systems. A number of dosimetry systems have been evaluated and issues affecting their performance have been investigated. The potential value of three-dimensional dosimetry systems has been explored.

Morbidity following salvage esophagectomy for squamous cell carcinoma: the MD Anderson experience.

The survival advantage associated with the addition of surgical therapy in esophageal squamous cell carcinoma (ESCC) patients who demonstrate a complete clinical response to chemoradiotherapy is unclear, and many institutions have adopted an organ-preserving strategy of selective surgery in this population. We sought to characterize our institutional experience of salvage esophagectomy (for failure of definitive bimodality therapy) and planned esophagectomy (as a component of trimodality therapy) by retrospectively analyzing patients with ESCC of the thoracic esophagus and GEJ who underwent esophagectomy following chemoradiotherapy between 2004 and 2016. Of 76 patients who met inclusion criteria, 46.1% (35) underwent salvage esophagectomy. Major postoperative complications (major cardiovascular and pulmonary events, anastomotic leak [grade ≥ 2], and 90-day mortality) were frequent and occurred in 52.6% of the cohort (planned resection: 36.6% [15/41]; salvage esophagectomy: 71.4% [25/35]). Observed rates of 30- and 90-day mortality for the entire cohort were 7.9% (planned: 7.3% [3/41]; salvage: 8.6% [3/35]) and 13.2% (planned: 9.8% [4/41]; salvage: 17.1% [6/35]), respectively. In summary, esophagectomy following chemoradiotherapy for ESCC at our institution has been associated with frequent postoperative morbidity and considerable rates of mortality in both planned and salvage settings. Although a selective approach to surgery may permit organ preservation in many patients with ESCC, these results highlight that salvage esophagectomy for failure of definitive-intent treatment of ESCC may also constitute a difficult clinical undertaking in some cases.

Long-Term Outcomes of Management of Olfactory Neuroblastoma: MD Anderson Experience

Long-Term Outcomes of Management of Olfactory Neuroblastoma: MD Anderson Experience

Clinical and Economic Burden of Respiratory Viral Infections in Hematopoietic Stem Cell Transplant Recipients: The MD Anderson Experience

BackgroundRespiratory syncytial virus (RSV), parainfluenza virus (PIV) and influenza virus (Flu) are common respiratory viral infections (RVIs) implicated in hematopoietic stem cell transplant (HSCT) recipients. Despite their possible association with high rates of pneumonia and mortality, their clinical and economic burden has not been well studied.MethodsHSCT recipients with documented RVI who were treated at our institution between September 2012 and October 2015 were included in the study. We used Vizient (formerly University Health Consortium) clinical database to collect and compare total costs, including length of stay, ICU admission rates, intravenous immunoglobulin use, steroid use, and mortality rates among RVIs in HSCT recipients. Encounter-specific demographics, risk factors, underlying cancer, and outcomes were also collected. Multiple linear regression analyses were applied to identify predictors of higher total cost associated with RVI in HSCT recipients at MD Anderson.ResultsAverage total cost per encounter was $49,371 for RSV, $29,679 for PIV, and $15,077 for Flu. A total of 1,636 hospitalization days (d) were attributed to these RVIs with an average of 7 d per RSV, 8 d per PIV, and 5 d for Flu infection. The average ICU admission rate was 12% for RSV, 9% for PIV, and 4% for Flu. Around 11% of total RVI encounters had active graft-vs.-host disease at the time of their RVI. Out of the patients with upper respiratory infection, 20% RSV, 44% PIV, and 21% Flu progressed to pneumonia during the 28 d of the study period. Of the 246 total RVI encounters, overall all-cause mortality rate was 6% (RSV: 8% [8/98], PIV: 1% [1/70] and Flu: 8% [6/78]). Length of stay, ICU admission, and receiving intravenous immunoglobulin were strong predictors of higher cost for all RVIs.ConclusionThis study underscores the significant impact of RVIs in terms of economic and clinical burden in HSCT recipients. Major differences in total costs per encounter across the three RVIs were observed. This cost and clinical data may be helpful for future cost effectiveness studies in this population.Disclosures All authors: No reported disclosures.

Postoperative local-regional radiation therapy in the treatment of parathyroid carcinoma: The MD Anderson experience of 35 years

PurposeWe aimed to investigate outcomes of locoregional radiation therapy (XRT) in parathyroid carcinoma (PC) patients at a single institution over 35 years. Methods and materialsRetrospective review of PC patients who received postoperative locoregional XRT (1980-2015). Patients were grouped according to XRT after PC initial operation or after salvage surgery. All patients with a histopathological diagnosis of PC who had postoperative locoregional XRT at our institution were included. All patients with a histopathological diagnosis of uncertain malignancy, suggestive for malignancy, or atypical parathyroid tumors and those who had XRT outside our institution were excluded. ResultsEight patients received XRT, 4 in each group, with a median follow-up of 12.5 years. The 4 patients who had XRT after initial surgery all had an oncologic operation, including ipsilateral thyroid lobectomy and central neck dissection, and all of these patients were disease-free at last follow-up. Of the 4 patients who received XRT after salvage surgery, only 1 remained disease free. There were no major complications/long-term side effects associated with XRT. ConclusionsXRT is well tolerated as postoperative locoregional treatment of patients with PC. Whether it is needed, and the timing of administering XRT, remains to be established.

A Clinical, Radiologic, and Pathologic Review of Astroblastoma: The MD Anderson Experience (P5.164)

A Clinical, Radiologic, and Pathologic Review of Astroblastoma: The MD Anderson Experience (P5.164)

Routine Clinical Testing for Actionable Mutations in CLL Using Endcll Assay V1: The Initial MD Anderson Experience

Background:Recent large scale genomic profiling and clinical correlation studies of chronic lymphocytic leukemia (CLL) identified clinically significant gene mutations with important clinical prognostic and potential therapeutic implications. Integration of individual clonal and subclonal gene mutation information with existing prognostic markers such as somatic hypermutation and chromosomal aberrations provide comprehensive risk stratification for CLL patients. In addition, mutations in BTK and PLCG2 are associated with resistance to targeted therapies using BTK inhibitors (ibrutinib). We implemented routine clinical testing for CLL patients. We describe our initial experience with EndCLL Assay V1, a high yield targeted NGS assay for routine clinical testing of clinically significant mutations in CLL and B-cell neoplasms.Materials and Methods:DNA from total of 376 blood or bone marrow samples containing >10% CLL cells were tested during the panel validation and subsequent routine clinical testing. Targeted sequencing was performed on 29 genes reported to be mutated in CLL and other B-cell neoplasms. These include ATM, BIRC3, BTK, CALR, CARD11, CD79A, CD79B, CHD2, CSMD3, CXCR4, DDX3X, EZH2, FAT1, FBXW7, KLHL6, LRP1B, MAPK1, MUC2, MYD88, NOTCH1, PLCG2, PLEKHG5, POT1, SF3B1, SPEN, TGM7, TP53, XPO1 and ZMYM3. Panel design included a combination of hotspots, limited exons and all exon coverage as required to detect known clinically significant mutations in the genes targeted in the panel. A total of 500 ng input DNA was used to prepare sequencing libraries using Agilent Haloplex HS chemistry, which incorporates unique molecular barcodes in each DNA molecule being sequenced. Sequencing was performed on MiSeq sequencers (Illumina) followed by data analysis on Agilent SureCall v3.0. The average per base coverage depth ranged from 1500x to 4000x based on the number of samples per run. The analytical sensitivity of the assay was determined to be at 2% to 5% for reliable and reproducible detection of mutations depending on the sequencing coverage and percentage of mutant reads.Results:For cases with available information, the average age was 63.3 years (range: 22-87, median: 64). The male:female ratio was 2:1 and the ratio of cases with unmutated:mutated IGHV was 1.2:1. Positive FISH results for -11q, +12, -13q and -17p were detected in 18%, 23%, 59% and 15% cases respectively. Out of 376 samples tested, 249 (66.2%) showed at least one mutation. Average number of genes mutated per sample was 1.1 (range: 0-5, median: 1) and the average number of total mutations per sample was 1.4 (range 0-7, median: 1). Top 10 mutated genes included TP53, SF3B1, NOTCH1, ATM, BIRC3, XPO1, MYD88, SPEN, BTK and KLHL6 (Figure 1). Patterns of co-mutations and mutual exclusivity were observed (Figure 1). Top 10 mutations (hotspots) are listed in the table. Mutations in 3’UTR of NOTCH1 were detected in 5/376 (%) cases. Resistance mutations in BTK codon 481 were detected in 10 patients on ibrutinib treatment, including 5 cases with >1 mutations and 2 cases with subclonal mutations indicating early treatment resistant clone. Clinical findings in all 10 cases were consistent with proven or emerging treatment resistance. No mutations were detected in PLCG2 (codons 646-685). One patient initially on ibrutinib and on idelalisib treatment showed acquisition of 17p deletion and a subclonal TP53 mutation at the time of ibrutinib resistance and progression to an aggressive disease course. Use of molecular barcodes allowed efficient detection of low level subclonal mutations. Correlations with a comprehensive set of clinicopathologic parameters as well as treatment outcomes are in progress.Conclusion:The targeted EndCLL Mutation Assay V1 allowed a high yield detection of clinically significant mutations in 66% of the patient samples using a clinically sustainable panel design accommodating up to 24 multiplexed samples in a single sequencing run. Use of molecular barcodes allows removal of PCR duplicates and enables accurate calling of subclonal mutations for prognostication. This was evident in simultaneous detection of subclonal BTK mutations allows early detection of emerging ibrutinib resistant clone while obtaining additional prognostic information. Overall, the EndCLL Assay V1 is a valuable addition for CLL patient care. [Display omitted] [Display omitted] DisclosuresJain:Incyte: Research Funding; BMS: Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; Novimmune: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Seattle Genetics: Research Funding; Abbvie: Research Funding; Infinity: Research Funding; Novartis: Consultancy, Honoraria; Genentech: Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Servier: Consultancy, Honoraria. Wierda:Gilead: Research Funding; Genentech: Research Funding; Acerta: Research Funding; Novartis: Research Funding; Abbvie: Research Funding.

High Risk Diffuse Large B Cell Lymphoma: A Comparison of Aggressive Subtypes Treated with Dose Adjusted Chemotherapy-the University of Texas MD Anderson Experience

Background: Diffuse large B cell lymphoma (DLBCL) is the most common type of non Hodgkin lymphoma (NHL).Nearly 50% of high-risk DLBCL patients are not cured with standard rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP). High risk DLBCL may be defined as double hit lymphoma (DHL, translocation of MYC and BCL2 or BCL6), double expressor lymphoma (DEL, over expression of MYC and BCL2), high risk international prognostic index (IPI) of 3-5, high Ki-67, and non-germinal center subtype (non-GCB). The majority of DHL cases occur in the GCB subtype, as opposed to the majority of DEL cases which occur in non-GCB. Hence we sought to compare different high risk subsets treated with dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone and rituximab (DA) EPOCH-R. In single arm phase II clinical trials, dose adjusted (DA) EPOCH-R has shown promising results, with potential greater efficacy in the GCB subtype in subset analyses (Wilson et al, Hematologica 2012). A randomized phase III study comparing RCHOP with (DA) EPOCH-R in newly diagnosed DLBCL has completed accrual, with highly anticipated results due in late 2016.Methods: We conducted a retrospective reviewof all consecutive, newly diagnosed DLBCL patients treated with (DA) EPOCH-R at MD Anderson Cancer Center from 2010 to 2014. Eligible patients were 18 years or greater, had high-risk DLBCL as determined by the treating physician, and had available data of treatment and response. The cell of origin subtype was determined by immunohistochemistry using Hans algorithm, and MYC and BCL2 positivity were defined as BCL2 positive in at least 70% and MYC positive in at least 40% of cells. DHL was defined as rearrangement of MYC and BCL2 or BCL6 by fluorescent in situ hybridization. The objectives were to analyze demographic, prognostic, and treatment variables in comparison with clinical response and survival outcomes in three sub groups which included 1. DHL (GCB) 2. DLBCL without MYC and BCL2 expression (GCB), and 3. DEL (GCB and non GCB). Complete response (CR), overall survival (OS) and progression free survival (PFS) were calculated using standard methods. Statistical analysis was done using Fishers exact test or Chi-square test / Kruskal-Wallis test. Kaplan-Meier method was used for time-to-event analysis including overall survival and progression free survival. The Log-rank test was used to evaluate the difference in time-to-event endpoints between patient groups.Results: We identified 233 high risk DLBCL patients treated with (DA) EPOCH-R. After filtering the data to identify patients which were included in our three groups, we identified 22 patients with DHL (GCB), 46 patients with non DEL (GCB), and 16 with DEL. The demographic features and outcomes are mentioned in the table 1 below. The DHL group had more frequent bone marrow (BM) involvement, and the DHL and DEL groups were more frequently age >60 years and high IPI in comparison to the non DEL GCB group. The CR rate, OS and PFS at 1 year were not significantly different between these three groups. Figure 1 highlights the OS (A) and PFS (B) results of each group.Conclusions: (DA) EPOCH-R is highly effective in patients with subsets of patients with high-risk DLBCL and may be able to overcome prognostic factors which have been shown to be adverse with RCHOP therapy. The results of this retrospective study suggest that OS in DHL, DEL and non DEL (GCB) are not statistically different. Hence, intensive chemotherapy with (DA) EPOCH-R could be considered as a frontline treatment option for patients with high risk DLBCL, pending further confirmation in randomized trials. [Display omitted] [Display omitted] DisclosuresOki:Novartis: Research Funding. Fowler:Infinity: Consultancy, Research Funding; Roche: Consultancy, Research Funding; TG Therapeutics: Consultancy; Celgene: Consultancy, Research Funding; Jannsen: Consultancy, Research Funding; Gilead: Research Funding. Wang:Pharmacyclics: Research Funding; Juno Therapeutics: Research Funding; Acerta Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; BeiGene: Research Funding; Kite Pharma: Research Funding; Onyx: Research Funding; Asana BioSciences: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Fayad:Seattle Genetics: Consultancy, Research Funding. Westin:ProNAi: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Chugai: Membership on an entity's Board of Directors or advisory committees.

Outcomes of Relapsed Core Binding Factor Acute Myeloid Leukemia: an MD Anderson Experience

Outcomes of Relapsed Core Binding Factor Acute Myeloid Leukemia: an MD Anderson Experience

Continuation of trastuzumab beyond disease progression in HER2-positive metastatic gastric cancer: the MD Anderson experience.

Despite the wide spread use of trastuzumab in human epidermal growth factor receptor 2 (HER2) overexpressing metastatic gastric cancer patients, its optimal duration of administration beyond first-line disease progression is unknown. In HER2 overexpressing metastatic breast cancer, trastuzumab continuation beyond first-line disease progression has shown improvement in time to progression (TTP) without an increased risk of treatment related toxicity. HER2-overexpressing metastatic gastric cancer patients were identified from our database between January 2010 and December 2014. We retrospectively reviewed the medical records of 43 patients who received trastuzumab in combination with chemotherapy as first-line and continued trastuzumab beyond disease progression. Forty-three cases were identified, 27 males (62.8%), median age of the patients was 58 years. Thirty-five (81.4%) presented with stage 4 as their initial presentation. Eighty one percent had 3+ HER2 overexpression by immunohistochemistry (IHC) and 18% had 2+ HER2 overexpression confirmed by fluorescence in situ hybridization (FISH). Thirteen (52%) were moderately differentiated, 16 (37.1%) were poorly differentiated. The most common sites of metastasis were liver 35 (81.4%) and lung 14 (32.5%). The most commonly used first-line regimen was oxaliplatin, 5-fluorouracil (5-FU), and trastuzumab in 22 (51.1%) patients. Twenty-five (58.1%) patients received irinotecan, 5-FU and trastuzumab in the second-line. Progression-free survival (PFS) was 5 months (95% CI: 4.01-5.99 months). Five patients are still alive and excluded from calculating the median overall survival (OS) which was 11 months (range, 5-53 months) for the remaining 20 subjects of this second-line group. Trastuzumab was not discontinued due to side effects in any of the study population. In conclusion, this retrospective analysis suggests that continuation of trastuzumab beyond disease progression in patients with HER2-overexpressing metastatic gastric cancer is feasible and safe. Randomized studies are warranted.

Preanalytic Variables in Cytology: Lessons Learned From Next-Generation Sequencing-The MD Anderson Experience.

Context .- As our understanding of genomic alterations underlying solid tumor malignancies continues to evolve, molecular testing of tumor samples is increasingly used to guide therapeutic management. Next-generation sequencing (NGS) provides a novel platform for the simultaneous screening of multiple genes using small amounts of DNA. Several recent studies have described NGS mutational analysis using cytologic specimens. The cytopathologist's role in specimen assessment and triaging is critical to effectively implementing NGS in routine cytology practice. Objectives .- To review the NGS experience and a variety of preanalytic factors that affect NGS success rates of cytologic specimens at our institution. Data Sources .- To evaluate cytology specimen adequacy rates for NGS, we reviewed a 14-month period of image-guided fine-needle aspiration and core needle biopsies, used for testing. In addition, we reviewed data from our previously published studies to evaluate preanalytic factors affecting NGS success in these specimens. Conclusions .- Identifying factors that affect NGS success rates in cytology specimens is crucial for a better understanding of specimen adequacy requirements and for proper use of limited-volume tissue samples. In our practice, which uses direct smears as well as cell block sections, NGS success rates in core needle biopsy and fine-needle aspiration samples are comparable. The chance of successful testing is further increased by procuring concurrent fine-needle aspiration and core needle biopsy samples. The type of glass slides used for direct smears and the method of tissue extraction affect our DNA yield. Validating a DNA input for cytology samples that is lower than that recommended by the manufacturer has significantly increased our NGS success rate.

Continuation of trastuzumab beyond disease progression in patients with metastatic gastric cancer: A retrospective analysis of 25 cases—The MD Anderson experience.

e15560Background: Despite the widespread use of trastuzumab in the management of patients with Human Epidermal growth factor receptors (HER2) - overexpressing metastatic gastric cancer, its optimal...