ALBERT

Description: Myelodysplastic syndromes (MDS) are a complex, heterogeneous group of disorders characterized by the accumulation of somatic mutations in combinations that vary between patients. While individual mutations have been identified that can risk stratify patients or identify targets for therapies, these findings have been relevant to only a minority of patients, as MDS is a disease not of individual mutations but of combinations of genes acting in molecular networks corresponding to several functional and biological pathways. Further, although two patients with MDS may not have mutations in common, they may share a network affected by similar genes. We performed exome sequencing of 201 samples from the bone marrow and peripheral blood of patients with MDS, MDS/MPN, and secondary AML (sAML). Network interactions were retrieved from several publically available databases (InACT, MINT, STRING, etc) and uploaded into cytoscape (an open source software platform for visualizing molecular interaction networks and biological pathways). Functional interactions and pathways were uploaded from Reactome and visualized in cytoscape using Reactome Functional Interaction (FI) network function (Reactome WIKI). Survival analyses were calculated from time of diagnosis to last follow up or death on samples with clinical data. Overall, 3452 mutations were detected with a median of 25 mutations per sample. Network-based analyses identified 745 genes with 293 interactions. Pathway enrichment analysis of the network identified novel pathways that have not been described previously in MDS including: Robo receptor signaling pathway, EphB-Abl signaling pathway, amb2 integrin signaling pathway and NOD-like receptor pathway. Standard clustering analysis (networks with high connections between nodes within the cluster but sparse connections with nodes in different clusters) identified 6 molecular subtypes of MDS, Figure 1. Pathway enrichment analysis of each subtype identified distinct pathways for each: subtype 1 was enriched mainly in immune mediated pathways, RAS/RAF/MAP kinase signaling pathway, EGFR signaling pathway, VEGF signaling pathway, and ERBB signaling pathway; subtype 2 enriched in spliceosome and RNA polymerase transcription pathways; subtype 3 enriched in mitosis and cell cycle pathways; subtype 4 enriched in cadherin and Wnt signaling pathways; subtype 5 enriched in DNA and histone methylation pathways; and subtype 6 with TP53 and DNA damage pathways. To determine the biological importance of the identified subtypes on outcome, we investigated whether each subtype affected clinical characteristics and overall survival. Overall, clinical data was available for 126 patients. Median age was 70 years, 66% have MDS, 17% MDS/MPN, and 17% s AML, 53% have low risk, 21% intermediate, and 26% high risk by the Revised International Prognostic Scoring System (IPSS-R). Clinical characteristics correlated with molecular subtypes: subtype 6 patients were older (median age 76) with higher blasts percentage (median 7%), 50% had sAML, and 20% RAEB-2 (higher risk by IPSS-R), whereas subtype 3 patients were younger (median age 65), has lower blasts percentage (median 2%) and 83% of them had lower risk MDS by IPSS-R. Excluding samples with overlapping subtypes, the median overall survival for patients with subtype 1,2,3,4,5,6 was 33.0, 24.6, 46.6, 22.9, 25.7, 6.6 months, respectively, p= 0.002. Given similar survival for subtypes 2,4, and 5, these were combined in one group, Figure 1. To further identify potential genes in our network for targeted therapies, we searched the publically available targeted therapies databases (TARGET and Therapeutic Target Database). We found 30 potential compounds either in clinical trials or under development that could be explored in MDS. In conclusion: network-based analyses defined molecular subtypes of MDS that were predictive of survival. It also identified potential targets for novel therapies that are in clinical trials or under development. These subtypes may be useful in the development of precision medicine strategies that are specifically directed at the pathways that are enriched in each subtype. Figure 1. Network-based analysis subtypes of MDS and overall survival Figure 1. Network-based analysis subtypes of MDS and overall survival Disclosures Sekeres: TetraLogic: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees.

Description: TET2 mutations are the most common somatic genetic lesions in myeloid neoplasms. TET2 mutant clones have been found also in healthy individuals, increase with age, and convey an increased risk for myeloid clonal diseases. The TET2 gene is very polymorphic, with hundreds of single nucleotide polymorphisms (SNPs) of unknown clinical impact, but with some variants that may be pathogenically important. Similarly, somatic mutations affect all portions of the gene, and can be missense or truncating, homo-, hemi- and heterozygous. While the majority of TET2 mutations are ancestral, they can also be subclonal, implicating the clonal architecture in the consequences of TET2 lesions. This diversity may be hampering establishment of the clear prognostic impact of TET2 mutations. Taking advantage of a large cohort of patients (pts, N=4985 including 1616 MDS, 871 MDS/MPN, 1782 pAML, 304 sAML, 333 MPN, and 79 therapy-related MDS/AML/MDS-MPN) analyzed by targeted deep sequencing for TET2 and other common myeloid lesions, we examined the distribution and impact of TET2 mutations. DNA sequencing of all coding exons of TET2 and 61 other genes representing the most common somatic mutations in myeloid neoplasms. Nonsynonymous alterations not present in SNP database (dbSNP) were annotated as somatic mutations or SNPs if present in myeloid and T cells whenever available. Nonsynonymous alterations not in dbSNP or ExAC databases and not confirmed to be somatic were excluded. Overall, TET2 somatic mutations (TET2mut) were present in 920 pts (18%); 38% of MDS/MPN, 19% pAML, 16% MPN, 16% sAML, 12% MDS, and 13% of therapy related MDS/AML/MDS-MPN. Mutations included 16% missense, 33% frameshift deletions, 18% frameshift insertions, and 33% nonsense. TET2mut pts were older than those with TET2 wild type (TET2wt, 72 vs. 67 yrs, p

Description: Background Achieving a complete remission (CR) in patients with newly diagnosed acute myeloid leukemia (AML) after induction chemotherapy with cytarabine and an anthracycline (7+3) remains an important treatment goal associated with better overall survival (OS). Approximately 25-30% of younger, and up to 50% of older patients (pts) fail to achieve CR. AML pts with residual leukemia at day 14 receive a second cycle of the same regimen; whether these pts have worse survival than pts not requiring re-induction is unclear. Information on pts with primary refractory AML and the best treatment strategy in this setting are limited. Methods Pts with newly diagnosed AML treated at our institution between 1/2000 and 1/2015 were included. Pts received standard induction chemotherapy with cytarabine for 7 days and an anthracycline for 3 days (7+3). Bone marrow biopsies were obtained at day 14 and a second cycle of the same regimen (7+3 for younger adults, 5+2 for older adults) was given to pts with residual leukemia (blasts 〉 5%). All responses were assessed at day 30 +/- 5 days post induction. Response was defined as CR and CR with incomplete hematologic recovery (CRi) or platelet recovery (CRp) per International Working Group (IWG) 2003 response criteria. Cytogenetic risk stratifications were based on CALGB/Alliance criteria. OS was calculated from the time of diagnosis to time of death or last follow up. A panel of 62 gene mutations that have been described as recurrent mutations in myeloid malignancies was used to evaluate whether genomic data can be used to predict response. Results: Among 227 pts with AML, 123 received 7+3 and had clinical and mutational data available. Median age was 60 years (range, 23-82). Median baseline WBC was 8.2 X 109/L (range, 0.3-227), hemoglobin 8.9 g/L (range, 4.7-13.8), platelets 47 X 109/L (range, 9-326), and BM blasts 46% (range, 20-95). Cytogenetic risk groups were: favorable in 12 (10%), intermediate in 68 (56%) [normal karyotype in 44 (36%)], and unfavorable in 42 (34%). A total of 93 pts (76%) responded, 69 (74%) received 1 cycle of induction and 24 (26%) required re-induction at day 14 due to residual leukemia. A total of 39 pts (32%) received allogeneic stem cell transplant (ASCT): 18 (46%) from a matched sibling donor, 16 (41%) from a matched unrelated donor and 5 (13%) had an umbilical cord transplant. With a median follow up of 13.5 months, the median OS for the entire group was 13 months (m, range, 0.1-120). The median OS for pts who failed 1-2 cycles of 7+3 was significantly worse than pts who responded (median 2.6 vs 16.9 m, p = 0.002). When pts undergoing ASCT were censored, the median OS was 2.3 vs 9.9 m, p= 0.003, respectively. Overall, 33 pts (27%) had residual leukemia at day 14 and received re-induction, 24 (72%) achieved a response at day 30+/- 5 days. The median OS for pts who received re-induction was inferior compared to pts who did not (10.1 vs. 16.1 months, p= 0.02). When pts who received ASCT were censored, the OS was similar (8.5 vs. 7.4 months, p = 0.49, respectively). Among the 30 pts with persistent disease following induction therapy at day 30, 11 (37%) died from induction complications, 6 (20%) received salvage therapy with mitoxantrone/etoposide/cytarabine, 3 (10%) received high dose cytarabine, 2 (7%) received azacitidine, and 8 (27%) received best supportive care. Among pts who received salvage chemotherapy 56% achieved CR and proceeded with ASCT. Two pts had ASCT with residual leukemia and relapsed within 3 m of ASCT. Pts who received ASCT after induction failure had a significantly better OS compared to non-transplant pts (median OS 22.0 vs. 1.4 months, p 〈 0.001, respectively); however, this benefit was only seen in pts who had ASCT in CR. We then investigated if genomic mutations can predict response or resistance to chemotherapy. Out of the 62 genes tested, only a TP53 mutation was associated with resistance, p = 0.02. Further, pts with TP53 mutations had significantly inferior OS compared to TP53 wild type regardless of ASCT status (1.4 vs 14.8 m, p〈 0.001) Conclusion: Pts with newly diagnosed AML who fail induction chemotherapy with a 7+3 regimen have a poor outcome. Re-induction with the same regimen at day 14 for residual leukemia converted most non-responders to responders, but was associated with worse OS. ASCT improves outcome only in pts who achieve CR with salvage therapy. TP53 mutations predicted resistance to chemotherapy with 7+3. Disclosures Carew: Boehringer Ingelheim: Research Funding. Sekeres:TetraLogic: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees.

Description: Background Acute myeloid leukemia (AML) is a complex, heterogeneous neoplasm characterized by the accumulation of complex genetic alterations that are responsible for the initiation and progression of the disease. Secondary AML (sAML) represents a progression from antecedent hematologic disorders such as myelodysplastic syndromes (MDS) or myeloprolifrative neoplasms (MPN). Certain acquired mutations have been reported to be specific for sAML when compared to primary AML (pAML), but many limitations exist when cytogenetic grouping or other parameters are taken into account. In addition, some mutations have been shown to impact survival in some studies, but not others. Methods We performed targeted deep sequencing on samples from bone marrow and peripheral blood of pts diagnosed with sAML and pAML and treated at our institution between 1/2003-1/2013. Additional data on pAML was added from The Cancer Genome Atlas (TCGA). A panel of 62 gene mutations described as frequently recurrent mutations in myeloid malignancies were assessed. Cytogenetic grouping was defined by CALGB/Alliance criteria. Differences were compared using Fisher's exact test and the Mann-Whitney U test for categorical and continuous variables, respectively. Overall survival (OS) was calculated from the time of diagnosis to last follow up or death. Results: A total of 496 pts included: 273 with pAML and 223 with sAML. Comparing pAML to sAML, pts were younger (median age 59 vs. 68 years, p

Description: Introduction: Letermovir is a terminase complex inhibitor that was recently approved for prevention of cytomegalovirus (CMV) reactivation after allogeneic hematopoietic cell transplant (HCT). Its favorable side effect profile makes it an attractive alternative to other anti-CMV agents. Nevertheless, its use may present other challenges secondary to enzyme induction, leading to clinically significant drug-drug interactions. Voriconazole is widely used for prophylaxis against invasive fungal infections in the setting of HCT. By virtue of its hepatic metabolism mediated by CYP2C19, the package insert recommends close monitoring of voriconazole trough concentration when given concomitantly with letermovir. The objective of this study was to characterize the extent of interaction between voriconazole and letermovir in allogeneic HCT recipients. The study was approved by the institutional review board. Methods: Patient selection and data collection: An institutional database was queried to identify patients who underwent allogeneic HCT and received antifungal prophylaxis with voriconazole from November 2018 through July 2020. Per the institutional standard operating procedure (SOP), patients initially received intravenous micafungin 50 mg daily which was switched to voriconazole when oral drug administration became feasible. The voriconazole prophylactic dose was guided by CYP2C19 phenotype. Rapid metabolizers (harboring the gain of function variantCYP2C19*17) received 300 mg twice daily whereas others received 200 mg twice daily. Further dose adjustment was warranted if trough concentration, measured at least 5 days after starting voriconazole, did not fall within target range of 1 to 5.5 mg/L. Patients at risk for CMV reactivation who underwent HCT after SOP revision (November 2019) received prophylaxis with letermovir 480 mg daily on day +6 post HCT. After a retrospective review of electronic medical records, HCT recipients were divided into two cohorts;cohort 1included patients who received letermovir prophylaxis whereascohort 2comprised those who did not. Data extracted from medical records included: demographics, hematological disorder, voriconazole dose and trough concentration, and date of letermovir initiation. Statistical analysis: The Student's t-test was used to compare mean voriconazole trough plasma concentration between cohorts 1 and 2. The chi-squared/Fisher's exact test was used to compare rate of subtherapeutic voriconazole trough concentration. Multivariate logistic regression analysis was performed to determine the association between letermovir use and subtherapeutic voriconazole concentration after adjusting for age, gender, race, weight and voriconazole dose. All statistical analyses were performed in SAS (version 9.4) Results: 64 patients were identified (23 in cohort 1 and 41 in cohort 2). Baseline characteristics were comparable except for age (62.0±8.7 years in cohort 1 vs. 58.0±12.2 years, p=0.01); 39% of patients in cohort 1 and 30% in cohort 2 received voriconazole 300 mg twice daily upfront for prophylaxis due to the rapid CYP2C19 metabolizer phenotype whereas the rest received voriconazole 200 mg twice daily (p=0.6). There was no significant difference in mean voriconazole trough plasma concentration (p=0.5) or frequency of subtherapeutic trough (p=0.16) between cohorts 1 and 2 (Figure 1). Multivariate logistic regression analysis indicated that letermovir prophylaxis had no impact on subtherapeutic voriconazole concentration (OR: 0.4, 95% CI: 0.1-1.4, p=0.1). In the subgroup of patients who received voriconazole at 300 mg twice daily, the rate of subtherapeutic concentration did not differ significantly between cohorts 1 and 2 (p=1.0), whereas a non-significant trend in rate of subtherapeutic voriconazole concentration was noted in subgroup of patients who received the 200 mg dose (p=0.1,Figure 2) Conclusions: Our single center experience suggests there may not be a significant interaction between voriconazole and letermovir. Notably, patients receiving the 300 mg dose upfront may not require an additional dose increase to achieve a voriconazole trough within the recommended range despite the concomitant use of letermovir. Our group is collaborating with other centers to corroborate these findings, particularly in patients receiving the standard voriconazole prophylactic dose of 200 mg. Disclosures Grunwald: Forma Therapeutics:Research Funding;Agios:Consultancy;Abbvie:Consultancy;Trovagene:Consultancy;Daiichi Sankyo:Consultancy;Astellas:Consultancy;Daiichi Sankyo:Consultancy;Trovagene:Consultancy;Trovagene:Consultancy;Premier:Consultancy;Astellas:Consultancy;Astellas:Consultancy;Genentech/Roche:Research Funding;Premier:Consultancy;Genentech/Roche:Research Funding;Genentech/Roche:Research Funding;Premier:Consultancy;Janssen:Research Funding;Merck:Consultancy;Forma Therapeutics:Research Funding;Incyte:Consultancy, Research Funding;Celgene:Consultancy;Incyte:Consultancy, Research Funding;Incyte:Consultancy, Research Funding;Pfizer:Consultancy;Celgene:Consultancy;Celgene:Consultancy;Cardinal Health:Consultancy;Merck:Research Funding;Daiichi Sankyo:Consultancy;Agios:Consultancy;Abbvie:Consultancy;Merck:Consultancy;Amgen:Consultancy;Merck:Consultancy;Amgen:Consultancy;Abbvie:Consultancy;Pfizer:Consultancy;Amgen:Consultancy;Pfizer:Consultancy;Agios:Consultancy;Cardinal Health:Consultancy;Forma Therapeutics:Research Funding;Cardinal Health:Consultancy;Janssen:Research Funding.Ai:Incyte:Speakers Bureau;Celgene:Speakers Bureau.Knight:Foundation for Financial Planning:Research Funding.Chojecki:Incyte:Research Funding;Novartis:Other: Investigator Meeting Attendance.Avalos:Juno:Membership on an entity's Board of Directors or advisory committees;Best Practice-Br Med J:Patents & Royalties: receives royalties from a coauthored article on evaluation of neutropenia.Copelan:Amgen:Membership on an entity's Board of Directors or advisory committees.

Description: INTRODUCTION -The prognosis of acute myeloid leukemia (AML) in elderly population is inherently poor due to multiple factors including: frailty, medical co-morbidities and high treatment related morbidity with traditional induction chemotherapy and presence of adverse risk cytogenetics in 17-20% of patients. For patients who are not candidates for intensive chemotherapy, outcomes in terms of complete response/complete response with incomplete hematologic response (CR/CRi) and median overall survival (mOS) have been evaluated using hypomethylating agents(HMA) including azacytidine (AZA)(CR/CRi=18-27.8%, mOS=10.4-24.5 months) and decitabine (CR/CRi= 18-47%, mOS= 7-7.8 months). Recently, addition of venetoclax to HMA has shown to further improve CR/CRi (75%) and mOS (17.5 m). We conducted a systematic review of literature to identify recent studies that were published between 2015-2020 with an aim is to evaluate newer combination drug regimens (CDR) involving hypomethylating agents (AZA and decitabine) in treating elderly patients with newly diagnosed AML. METHODS- A comprehensive literature search was conducted in PubMed, Embase, and Cochrane databases. We included phase I/II studies that used CDR with HMA in elderly patients with newly diagnosed AML. RESULTS- Initial database search lead to 1120 studies. After exclusion (duplicates, case reports/series, relapsed/refractory AML) final analysis included 12 studies (n=655). Seven phase I/II with CDR using decitabine (n=500) were included in our review. Drugs used in combination included gemcitabine ozagamicin (n=40, CR/CRi =45%, mOS= 7 m), cladribine and low dose cytarabine (n=118, CR/CRi= 68%, mOS =13.8 m), vadastuximab talirine (n=53, CR/CRi=70%, mOS=11.3 m) and selinexor (n=5, CR/Cri= 80%) . In addition, three studies compared outcomes of CDR involving decitabine with all trans retinoic acid (ATRA)(n=93, ORR=21.9% vs 13.5%, p=0.06; mOS= 8.2 m vs 5.1 m, p=0.006) or talacotuzumab (CR/CRi= 15% vs 11%, p=0.44; mOS= 5.36 m vs 7.26 m, p=0.78) or bortezomib (CR/CRi= 39% vs 38%, p=0.91, mOS=9.3 m vs 8.9,p=0.18) to decitabine alone. In addition, cladribine and low dose cytarabine with decitabine in patients with adverse cytogenetics showed a decent CR/CRi of 50%, mOS= 10.5 months. In TP 53 positive mutations, CR/CRi was 40% and mOS was 5.4 months. Five phase I/II studies using CDR with AZA (n=155) were included in our review. Drugs included midostaurin (n= 88 , CR/CRi=25-29% mOS= 6-8 m) and pracinostat (n= 50, CR/CRi =46% mOS=19.1 m), In addition, two studies compared outcomes using CDR involving AZA with panobinostat (n=22, CR= 22.4 vs 30.8%, OS at 1 year = 60% vs 70%) or entinostat (n=18, ORR= 0% vs 16.6%, mOS=6 m vs 13 m) to AZA alone. None of the two comparative CDR studies using AZA showed superior outcome compared to AZA alone. CONCLUSIONS - Novel drug combinations involving decitabine including cladribine and low dose cytarabine, vadastuximab talarine showed superior CR/CRi and mOS compared to decitabine alone used in historic studies. In addition, CR/CRi were similar to HMA and venetoclax combination. In small number of patients, CDR with selinexor also showed superior CR/CRi compared to decitabine alone. CDR involving decitabine and ATRA showed superior mOS in direct comparison with decitabine alone. In addition, cladribine, low dose cytarabine and decitabine has shown promising outcomes in patients with adverse cytogenetics. Among CDR involving AZA only Proctinostat showed superior CR/CRi and mOS compared to historic studies with AZA alone. A recent phase III study though involving this CDR in comparison with decitabine was terminated early due to lack of efficacy on preliminary analysis. The above listed efficacious CDR involving decitabine in phase I/II studies need to be evaluated in large, randomized trials to assess for definitive benefit. If proven efficacious in larger studies, they could serve as additional first line CDR options in addition to HMA and venetoclax in treating elderly patients with newly diagnosed AML. Disclosures No relevant conflicts of interest to declare.

Description: Background: Financial toxicity (FT) has been consistently demonstrated to a be a major contributor to morbidity and mortality in a variety of cancers. However, the vast majority of research examining this issue has been in solid tumors, and there has been less investigation of how this concept applies in malignant hematology and even fewer studies looking at an interventional model. This pilot study attempts to identify patients at high-risk due to FT in a busy clinical environment and improve clinical outcomes with comprehensive intervention. Methods: All patients seen at the Malignant Hematology Clinic at the Levine Cancer Institute, a tertiary hospital-based specialty practice, were surveyed at their visits over a six-month period. All patients were aged ≥18 years and diagnosed with hematologic malignancy or bone marrow failure syndrome. The survey consisted of the PROMIS Global-10 measure and two questions from the COST measure. FT was defined as scoring 5 or less (maximum: 10) in agreement with the COST questions: "I know that I have enough money in savings, retirement, or assets to cover the costs of my treatment" and "I am satisfied with my current financial situation." Patients with FT were entered into the interventional cohort and scheduled for a visit with a nurse navigator where they completed a standardized worksheet to identify gaps in care and opportunities for grant funding/other assistance. Patients were seen by a clinical pharmacist for copay review and discussion of assistance programs. Finally, patients were offered the services of a community pro-bono financial planner for help with budgeting, asset management, and general financial advice. Patients were tracked longitudinally for assistance provided, changes in PROMIS scores, and clinical outcomes. Categorical variables, including responses to survey questions, were summarized with frequencies and proportions, while continuous variables were summarized with medians and ranges. Correlation of FT screening scores and COST scores was assessed with Spearman's correlation. Baseline versus post-intervention PROMIS scores were compared with paired t-tests, while McNemar tests for agreement were used to compare ER and IP utilization 3 months prior versus post intervention. Results: A total of 107 patients were included in the intervention. Specific characteristics of the intervention population are listed in Table 1. FT screening scores were found to correlate with the full COST measure (Spearman correlation = 0.45, p

Description: Introduction Gleevec, Imatinib mesylate, is the first in class BCR-ABL tyrosine kinase inhibitor initially approved to treat CML. In February 2016, generic imatinib products became available. As generic products are not required to offer comparative efficacy and safety data, differences may arise. Small reports have found no significant differences in response durability and tolerability in patients transitioned from Gleevec to generic imatinib. Further, lower cost of generic products often influence treatment decisions and patient compliance. We sought to evaluate response durability, tolerability, financial costs, and adherence in patients with chronic phase CML (cpCML) who switched from Gleevec to generic imatinib and newly diagnosed cpCML patients initiated on generic imatinib. Methods We conducted a single-center, retrospective chart review of adult patients who received imatinib therapy for cpCML between June 1, 2015 to November 14, 2019. Patients who received ≥6 months of brand through the Specialty Pharmacy Service (SPS) at Atrium Health prior to switching to generic were included in Group 1 (Switch). Patients who initiated therapy with generic imatinib dispensed from SPS were included in Group 2 (New Start). Durability of response was described determined via peripheral blood BCR-ABL transcripts by PCR and reported major molecular response (MMR) after 12 months generic imatinib therapy. Additional factors characterizing the durability and tolerability of therapy included adverse effects due to drug, dose modifications, adherence rate, prescription cost per month, and frequency of switch between generic products. Results Of 298 patients assessed, 12 patients were evaluable. There were 7 Switch patients and 5 New Start patients. Figure 1. All 12 patients met WHO diagnostic cpCML criteria. No patients in either group had accelerated or blast phase CML, no patients received maintenance imatinib following allogeneic HCT. In the Switch Group, 4 patients (57%) achieved MMR after 12 months of generic therapy. Of the 3 patients that did not achieve MMR, 1 patient relocated prior to 12-month assessment, 1 patient was noted to be non-compliant, and 1 patient had several treatment delays and dose reductions due to toxicities. 1 New Start patient achieved MMR at 12 months. Of those not achieving MMR, 1 was started on a reduced dose (100 mg /day) due to renal dysfunction, 1 had a PDC of 49.10% due to treatment delays while receiving treatment for a different malignancy, and 2 patients had logarithmic decreases in BCR-ABL but had not crossed the MMR threshold after 12 months of therapy. 5 Switch patients (71.4%) reported at least 1 adverse effect related to therapy, 3 of these (42.9%) required dose reduction. The adverse effects requiring dose reductions in the New Start patients included thrombocytopenia (n=2) and myalgia (n=1). All New Start patients reported at least 1 adverse effect with none of these patients requiring a dose reduction. Cost stayed the same or was reduced for 85.7% of the Switch patients, 1 patient experienced a cost increase and did not have co-pay assistance, and 2 patients received copay assistance. Cost of generic therapy was 90% after 12 months on generic therapy for 71.4% Switch patients and 80% New Start patients. Table 1. and Table 2. Conclusion Patients with cpCML switched from brand to generic imatinib and patients newly started on generic imatinib appear to have durable responses and tolerance to generic imatinib. Dose reductions and non-adherence may have contributed to inadequate disease control in patients not achieving MMR in both groups. Patients switched from brand to generic imatinib may develop new side effects necessitating dose reduction. Thrombocytopenia may be more common in patients switched from brand to generic imatinib. Adherence to brand and generic imatinib is high and medication is affordable with most patients paying

Description: Background: Financial toxicity (FT) is defined as financial distress as a result of disease or treatment decisions. FT might be considered analogous to physical toxicity. Patients with high risk hematologic malignancies represent an especially vulnerable group for cost related issues due to heavy healthcare utilization, high costs associated with their treatment, and the potentially deadly consequences of treatment noncompliance. We hypothesized that comprehensive intervention on the financial aspects of care for these patients would lead to decreased mortality. Methods: All patients seen in Leukemia Clinic at the Levine Cancer Institute, a tertiary hospital-based specialty practice, were surveyed prior to their visit over a six-month period. All patients were aged ≥18 years and diagnosed with a high-risk hematologic malignancy (intermediate/high risk AML, high risk ALL, high or very high risk MDS, blast phase CML, or mixed phenotypic acute leukemia). The survey consisted of the PROMIS Global-10 measure and two questions from the COST measure. FT was defined as scoring 5 or less (maximum: 10) in agreement with the COST questions: "I know that I have enough money in savings, retirement, or assets to cover the costs of my treatment" and "I am satisfied with my current financial situation." Patients who met these criteria were entered into the interventional cohort and scheduled for comprehensive intervention based on availability of study staff. Scheduling was done anonymously and without prioritization of perceived need. The intervention consisted of a nurse navigator visit where patients completed a standardized worksheet to identify gaps in care and opportunities for grant funding/other assistance, a clinical pharmacist visit for medication copay review and discussion of assistance programs, and the services of a community pro-bono financial planner for assistance with budgeting, asset management, and general financial advice. Demographic/clinical data were abstracted from the medical record and patients were tracked longitudinally for clinical outcomes. Categorical factors were summarized with proportions and compared between groups with Fisher's exact tests, while continuous factors were summarized with medians and compared between groups with median two-sample tests. Overall survival (OS) was evaluated with Kaplan Meier methods and compared between groups with a log rank test. Cox proportional hazards models were utilized in model selection procedures for OS. Individual prognostics were identified with univariable models, then backward elimination and forward selection (entry/elimination criteria p = 0.10) were carried out to identify a final base model. This was utilized to estimate an adjusted HR for the intervention variable. Results: A total of 105 patients met criteria and were placed in the interventional cohort with the intention to receive the full intervention. Of these patients, 59 (56.2%) were able to be scheduled and receive the full intervention, while the remainder received standard care only. There were no significant differences between the groups when compared by gender, race, age, marital status, insurance type, FT screening score, therapy received, or disease type (Table 1). OS was significantly different between the two groups, with a mortality rate during the study period of only 27% for the patients that received the full FT intervention as opposed to 43% for the patients who received standard care. Adjusted OS at 6 months for the interventional cohort was 81.4% (95% CI 68.9%-89.2%) versus 73.9% (95% CI 58.7%-84.3%) for the non-intervention group; OS rates at 12 months were 73.0% (59.0%-82.9%) and 46.4% (28.9%-63.8%), respectively (Figure 1). On univariate analysis, intervention was significantly associated with survival (HR: 0.44, 95% CI: 0.22 - 0.86, p = 0.017). After adjusting for insurance, race, and age at survey, risk of death in those receiving the intervention was 0.47 times the risk of death in those without the intervention (95% CI: 0.23 - 0.98, p = 0.043). Conclusions: High risk hematologic malignancy patients are at high risk for increased complications due to financial concerns. Intervening on FT in a comprehensive way including navigators, pharmacists, and financial counselors is effective and leads to decreased mortality. Disclosures Knight: Foundation for Financial Planning: Research Funding. Ai:Incyte: Speakers Bureau; Celgene: Speakers Bureau. Chojecki:Incyte: Research Funding; Novartis: Other: Investigator Meeting Attendance. Copelan:Amgen: Membership on an entity's Board of Directors or advisory committees. Grunwald:Pfizer: Consultancy; Agios: Consultancy; Abbvie: Consultancy; Agios: Consultancy; Daiichi Sankyo: Consultancy; Agios: Consultancy; Cardinal Health: Consultancy; Incyte: Consultancy, Research Funding; Trovagene: Consultancy; Daiichi Sankyo: Consultancy; Astellas: Consultancy; Daiichi Sankyo: Consultancy; Trovagene: Consultancy; Abbvie: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Merck: Consultancy; Abbvie: Consultancy; Celgene: Consultancy; Janssen: Research Funding; Trovagene: Consultancy; Premier: Consultancy; Astellas: Consultancy; Astellas: Consultancy; Genentech/Roche: Research Funding; Premier: Consultancy; Premier: Consultancy; Amgen: Consultancy; Cardinal Health: Consultancy; Incyte: Consultancy, Research Funding; Celgene: Consultancy; Genentech/Roche: Research Funding; Genentech/Roche: Research Funding; Forma Therapeutics: Research Funding; Incyte: Consultancy, Research Funding; Merck: Research Funding; Janssen: Research Funding; Forma Therapeutics: Research Funding; Forma Therapeutics: Research Funding; Pfizer: Consultancy; Pfizer: Consultancy; Merck: Consultancy; Amgen: Consultancy; Merck: Consultancy; Cardinal Health: Consultancy.