Stanford Cancer Research Articles

Belumosudil Combination Therapy in Refractory Chronic Graft-Versus-Host Disease

Background: There are now 3 FDA approved oral drugs for chronic graft-versus-host disease (cGVHD) after 1-2 or more prior lines of therapy- ibrutinib, ruxolitinib and belumosudil. Encouraging overall response rates have been reported for all 3 agents; however, complete responses are rare and there are still a large number of patients who do not respond or lose the response over time. One of the approaches to overcome potential resistance to single agent use is to combine the new agents with each other or with other therapies (such as extracorporeal photopheresis (ECP), sirolimus, MMF) as there can be synergy across agents with different mechanisms of action. The 3 new drugs are all kinase inhibitors that block lymphocyte activation pathways and the production of proinflammatory cytokines. Preclinical studies showed their potential effects in cGVHD. Since the FDA approvals, it has been possible to use these drugs in various combinations for cGVHD treatment in daily clinical practice. In this retrospective review, we summarize our institution's real-world practice of using the ROCK2-inhibitor belumosudil in combination therapies since its FDA approval in July 2021. Methods: We conducted a retrospective chart review of patients treated with belumosudil in combination with other therapeutic agents at the Stanford Cancer Institute from July 2021 to July 2022. We collected descriptive statistics of standard outcomes of response as defined by the 2014 NIH Consensus Project on Criteria for Clinical Trials in cGVHD. Refractory cGVHD was defined as steroid-refractory or steroid-dependent cGVHD. Results: A cohort of 26 patients were evaluated (Table 1). The most common organ affected was skin (n = 20), followed by mouth (n = 19), eyes (n = 15) and joints/fascia (n=15). Patients were treated with a median number of 3 lines of prior therapies before initiating belumosudil. Combination therapies with belumosudil included several 3-4 drug combinations with concurrent use of ruxolitinib, ECP, prednisone, sirolimus or CNI. In instances in which belumosudil was combined with ruxolitinib, belumosudil was the add-on drug. The median follow-up period following initiation of belumosudil was 213.5 days. The overall response rate (ORR) following the addition of belumosudil was 77% (20/26). Responses to belumosudil used in combination were based on organ symptom scoring and global rating by clinician assessment according to the 2014 NIH Consensus Criteria and were seen in 85% (17/20) patients with skin involvement; 53% (8/15) patients with joint/fascial involvement, 33% (5/15) patients with eye involvement, 30% (3/10) patients with lung involvement, 11% (2/19) patients with mouth involvement, and 13% (1/8) patients with liver involvement (Table 2). No responses were seen in patients with GI (lower tract) involvement. No clinically evident adverse drug reactions occurred in the belumosudil combinations although variable dosing of the combined agents was used with the approved belumosudil dose of 200 mg po daily. Infectious adverse events occurred in 42% (11/26) of patients, consistent with the immunosuppressive effects of cGVHD therapies. Of these, 36% (5/14) was due to SARS-CoV2 infection, 29% (4/14) cytomegalovirus reactivation, 21% (3/14) bacterial infection, 7% (1/14) rhinovirus infection, and 7% (1/14) respiratory syncytial virus. The number of infection events with the new agent combination of belumosudil plus ruxolitinib was reviewed separately and was not increased over the other belumosudil combinations. No deaths have occurred in this cohort of 26 patients to date. Conclusion: In our institutional practice, administration of belumosudil in combination therapy appears safe, tolerable, and effective in patients with established, refractory cGVHD. The results of our retrospective study highlight the feasibility of the next phase of belumosudil research for combination therapy in this difficult-to-treat population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

NCOG-27. A SINGLE-INSTITUTION RETROSPECTIVE SERIES OF SARS-COV-2 INFECTION IN ADULT GLIOMA PATIENTS

Abstract A subset of cancer patients is particularly vulnerable to SARS-Cov-2 infection; however, real-world outcomes-based data on primary central nervous system tumor patients is sparse. This retrospective case series describes a cohort of adult glioma patients seen at Stanford Cancer Center between 1/20/2020 through 5/24/2022 who contracted SARS-Cov-2. We identified 18 patients with a diagnosis of glioma, with a median age of 54 years, who were infected with Covid-19. One patient contracted Covid-19 twice during this two-year period. Of these patients, four had pathology confirmed low-grade glioma, defined as oligodendroglioma or astrocytoma WHO grade 2, and 14 patients had high-grade glioma, defined as astrocytoma or glioblastoma WHO grade 4. Median KPS at time of infection was 70. Six individuals had notable cardiovascular comorbidities including coronary artery disease, obesity, and/or diabetes. All but one patient was vaccinated against Covid-19, and 6 were taking dexamethasone at the time of infection. Three patients required hospital admission for management of Covid-19 symptoms, although none required ICU-level of care. None died from Covid-related complications; however, two died from complications of their underlying cancer at the end of study. Our data suggest that glioma patients seen at Stanford Cancer Center do not experience an exceptionally high Covid-19 infectivity, hospitalization, or mortality rate, especially when compared to other vulnerable populations such as lung cancer patients. High vaccination rates, fairly low prevalence of cardiovascular comorbidities, and adherence to pandemic precautions among this cohort may have contributed to these results.

Charting the Course Toward More Equitable Health Care Systems.

Departments of Health Policy, Epidemiology and Population Health, and (by courtesy) Pediatrics, Stanford School of Medicine, Stanford, CA Adams receives funding from the Diabetes Research for Equity through Advanced Multilevel Science Center for Diabetes Translational Research (DREAMS-CDTR) (P30 DK092924) and the Stanford Cancer Institute (P30 CA124435). She is also supported by an endowment through the Stanford Cancer Institute as the Stanford Medicine Innovation Professor. The author declares no conflict of interest. Correspondence to: Alyce S. Adams, PhD, 300 Pasteur Drive, Room M121K, Stanford, CA 94305. E-mail: [email protected].

CT-095 Disparities and Incomplete Capture of Race/Ethnicity Data in Adults With Hematologic Malignancies Referred for Cellular Therapies

Numerous reports demonstrate disparities in access to care, clinical trial enrollment, and survival outcomes in various hematologic malignancies based on race/ethnicity. Based on 2020 US Census data, the Stanford Cancer Institute catchment area includes a population of 32% Non-Hispanic White (NHW), 32% Hispanic, 25% Asian, and 5% Non-Hispanic Black (NHB). To examine reporting of race/ethnicity and disparities in referral for, and receipt of, cellular therapies based on race/ethnicity in our region. In this retrospective review of patient electronic medical records, we assessed race and ethnicity among adults referred to Stanford for hematopoietic cell transplantation (HCT) and chimeric antigen receptor T-cell (CAR-T) between 2018 and 2022. Race/ethnicity data were evaluated as was receipt of cellular therapy. For the 3,532 referred patients identified, 49% (N=1,743) were NHW compared to 17% (N=599) Hispanic, 15% (N=522) Asian and 5% (N=104) NHB patients; 19% (N=672) of referred patients had unknown race/ethnicity. Among those referred, 48% (N=1,695) actually received HCT and 9% (N=333) received CAR-T. The racial/ethnic distribution of HCT recipients were proportional to the referral population: 49% (N=836) NHW, 18% (N=312) Hispanic, 16% (N=273) Asian, 6% (N=95) NHB, and 25% (N=418) unknown, while CAR-T recipients were somewhat less likely to be NHB than the referral population: 54% (N=181) NHW, 17% (N=59) Hispanic, 13% (N=42) Asian, 3% (N=10) NHB, and 25% (N=82) unknown. Social determinants of health were not routinely captured among referred or treated patients. Approximately 20% of adult patients referred and receiving cellular therapies have unknown race/ethnicity. Referred patients did not match our catchment area, with Hispanic patients comprising 50% fewer referrals than anticipated. The race/ethnicity of patients treated was overall consistent with the distribution of patients referred, suggesting that disparities are occurring more at the referral level. These data have prompted an interventional project aimed at better capturing race/ethnicity and social determinants of health among all adults referred for HCT and CAR-T cell therapy at Stanford.

Feasibility of large scale distress screening at an academic center and associated network sites using an adapted patient-reported outcome instrument and reflexive suicide screening.

278 Background: Regular distress screening of patients with cancer is mandated by cancer care guidelines, with 25-50% of patients with cancer experiencing some level of distress. The COVID-19 pandemic amplified symptoms of distress and shifted oncologic care delivery towards telemedicine. In light of challenges faced with implementation of such screening, especially during this pandemic, we sought to assess the feasibility of implementing patient-focused distress screening at a large academic cancer center and its associated network sites. Methods: We designed a modified distress screening tool with reflexive suicidality and mental health screening consisting of 1) Wellness Reflection, a questionnaire that incorporates questions from Patient-Reported Outcomes Measurement Information System-Global Health (PROMIS-GH) to monitor patients’ physical, mental, and social health and to assess patients’ needs for extra support, and 2) modified Patient Health Questionnaire 2+9 (PHQ 2+9) tool to screen for depression and suicide risk. This tool was used to triage patients in need of further assessment by the clinical team, including consideration for referrals to cancer supportive services. The two-tiered distress screening tool was delivered to patients at Stanford Cancer Center and 5 affiliate sites for in-person clinic visits starting September 2019. The Wellness Reflection was launched starting June 2020 for video visits. Results: From October 1, 2019 to May 14, 2021, 147,165 questionnaires representing 46,341 patients were collected. The overall Wellness Reflection questionnaire response rate was 55%; the video visit questionnaire response rate was ̃70%, higher than the in-person visit response rate of ̃50%. About 6% of questionnaires analyzed showed a request for more support, most commonly emotional and physical/symptom support, and this was consistent during the COVID-19 pandemic. 18.6% of questionnaire responses screened positive for further assessment, and those that triggered reflexive suicidality screening had a 17% positive PHQ 2+9 rate. Following assessment, 13,631 referrals to cancer supportive services were generated. Conclusions: The adoption of commonly available patient-reported outcome tools, including PROMIS-GH and PHQ 2+9, as a large-scale distress screening method for both in-person and tele-health clinic visits during the COVID-19 pandemic is feasible at a large academic cancer center and network sites. The volumes of positive screens and referrals were lower than expected despite broader implementation of distress screening and amplified symptoms of distress due to the pandemic.

An assessment of patient-provider communication surrounding tumor genetic profiling in thoracic oncology.

285 Background: Thoracic oncologists regularly order mutational testing for lung cancer, called the Stanford Actionable Mutation Panel (STAMP) at the Stanford Cancer Center, that assesses for somatic tumor based mutational testing. This project surveyed patients who had this testing and assessed their understanding of the test’s purpose and results in thoracic oncology. We also gathered information about which providers on the care team are conducting this counseling and time spent on patient education. Methods: This quality assurance project was deemed exempt from IRB review. We obtained an EHR query of patients who had the STAMP testing between July 2020 and July 2021, which was kept in a password protected file in a secured shared folder. Patients were contacted by phone using Doximity Dialer and answers were recorded in Redcap as the questionnaire was administered over the phone. Patient responses were labeled using a random number generator and no protected patient information was recorded. Results: The EHR query of patients who had the STAMP test performed in the last year resulted in 77 unique patients and 34 patients agreed to complete the survey. The majority of respondents (73.5%) knew that their physician or oncologist had ordered the STAMP test for them. Of those patients, the majority (84%) stated that their provider, most commonly their oncologist, explained the purpose of the test. The majority of respondents (64%) stated that their provider, most commonly their oncologist, had discussed the test results with them, which usually took approximately 5-10 minutes. Almost all respondents (93.8%) felt that they had time to ask the questions they had regarding their results. 43.8% of respondents stated that their test results changed their treatment options and 18.8% were unsure. Similarly, 43.8% of respondents stated that they had a targetable mutation, while 25% were unsure. Overall, 42.9% of respondents felt confident in their understanding of their test results, 33.3% were very confident, 4.8% felt neutral, and 19% were not confident in their understanding. Conclusions: In this single center survey, thoracic oncology teams appear to be communicating effectively with their patients about the purpose and results of molecular testing. However, patients were more uncertain about how the test influenced their treatment, identifying a potential area of improvement in patient education.

A brief report on the mutational landscape in non-small cell lung cancer of South Asian patients: Comparison at a US and an Indian Institution.

Background:Various molecular underpinnings of lung cancer have been noted in Asian populations, especially with targetable oncogenic drivers such as EGFR mutations and ALK rearrangements, although they have been lesser described in South Asian/Indian patientsMethods:Tumour molecular testing results from non-small cell lung cancer (NSCLC) patients with a name of South Asian origin and diagnosed from 2005 to 2019 at the Stanford Cancer Center in the United States were retrospectively reviewed and compared to the results of molecular testing from PGIMER in Chandigarh, India, from the patients diagnosed from 2011 to 2019Results:We identified 72 patients of South Asian (largely Indian) origin, of whom 64 patients (51% female) had mutational testing at Stanford. Of the tested patients, 33% of cases harboured either an EGFR exon 19 deletion or exon 21 L858R mutation, and 12.5% had ALK rearrangements. At PGIMER, a larger sample of 1,264 patients was identified (33% female), with 22.5% of patients having two main EGFR activating mutations, and 9.5% harbouring an ALK rearrangementConclusions:South Asian, largely Indian, patients with NSCLC appear to have a higher chance of harbouring EGFR mutations and ALK translocation as compared to Caucasians. The percentage of South Asian patients with these molecular abnormalities was largely similar in two different geographical locations. These findings corroborate prior single-institution findings and emphasise the importance of molecular testing.

Abstract 3603: Reverse fate mapping of CD19-targeted CAR T cells in patients with large B-cell lymphoma

Abstract Autologous T cells genetically engineered to express a chimeric antigen receptor targeting CD19 (CD19-CAR) have achieved high complete response rates in patients with hematologic malignancies, but >50% of patients progress following therapy. Here, we sought to understand key T-cell intrinsic factors impacting efficacy, namely CAR T-cell expansion, persistence, and homing to the tumor. Using an approach called reverse fate mapping, we followed individual T-cell clones at the single-cell level from pre-manufacture apheresis to the infusion product, tumor-involved lymph node, and blood at peak and late expansion in 12 adult patients with relapsed or refractory large B-cell lymphoma treated with axicabtagene ciloleucel, an FDA-approved CD19-CAR T-cell immunotherapy. The resulting CAR T-cell atlas comprises matched transcriptome (scRNA-seq) and surface protein expression (CITE-seq) for 322,028 cells from 44 samples, with 119,397 unique T-cell receptor (TCR) clonotypes identified. This atlas enabled us to ask questions like: “What were the phenotypes of the most successful CAR T-cell clones at the time of infusion or pre-manufacture apheresis?” We found that T-cell clonotypes with juvenile features at apheresis, including IL7R expression, were the most successful at expansion to higher frequencies in the infusion product, while clones with effector gene expression programs, such as those encoding perforin and granzymes, contracted between apheresis and product. Conversely, it was GZMK-expressing T cells in pre-manufacture apheresis that were dominant in the tumor early following CAR T-cell infusion. Further, T-cell clonotypes with active effector programs at infusion dominated at peak expansion. Finally, we defined active expression modules and pathways in the infusion product for CAR T-cell clones that homed to the tumor or became dominant at late expansion. These analyses pinpoint the molecular mechanisms that could be modulated to rationally steer CAR T-cell differentiation trajectories at the genetic or pharmacological level. This work was supported in part by the Parker Institute for Cancer Immunotherapy, California Institute for Regenerative Medicine, Kite Pharma, and Stanford Cancer Institute. Citation Format: Zinaida Good, Mark P. Hamilton, Jay Y. Spiegel, Sreevidya Kurra, Moksha Desai, Snehit Prabhu, Eric Yang, Michael G. Ozawa, Paul J. Hanson, Fang Wu, Matthew J. Frank, John H. Baird, Lori Muffly, Gursharan K. Claire, Juliana Craig, Katherine A. Kong, Dhananjay Wagh, John Coller, Sylvia K. Plevritis, Bita Sahaf, David B. Miklos, Crystal L. Mackall. Reverse fate mapping of CD19-targeted CAR T cells in patients with large B-cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3603.

Accuracy of Electronic Medical Record Follow-Up Data for Estimating the Survival Time of Patients With Cancer.

For real-world evidence, it is convenient to use routinely collected data from the electronic medical record (EMR) to measure survival outcomes. However, patients can become lost to follow-up, causing incomplete data and biased survival time estimates. We quantified this issue for patients with metastatic cancer seen in an academic health system by comparing survival estimates from EMR data only and from EMR data combined with high-quality cancer registry data. Patients diagnosed with metastatic cancer from 2008 to 2014 were included in this retrospective study. Patients who were diagnosed with cancer or received their initial treatment within our system were included in the institutional cancer registry and this study. Overall survival was calculated using the Kaplan-Meier method. Survival curves were generated in two ways: using EMR follow-up data alone and using EMR data supplemented with data from the Stanford Cancer Registry/California Cancer Registry. Four thousand seventy-seven patients were included. The median follow-up using EMR + Cancer Registry data was 19.9 months, and the median follow-up in surviving patients was 67.6 months. There were 1,301 deaths recorded in the EMR and 3,140 deaths recorded in the Cancer Registry. The median overall survival from the date of cancer diagnosis using EMR data was 58.7 months (95% CI, 54.2 to 63.2); using EMR + Cancer Registry data, it was 20.8 months (95% CI, 19.6 to 22.3). A similar pattern was seen using the date of first systemic therapy or date of first hospital admission as the baseline date. Using EMR data alone, survival time was overestimated compared with EMR + Cancer Registry data.

Characterization of Metastatic Non-Small Cell Lung Cancer and Oligometastatic Incidence in an Era of Changing Treatment Paradigms

Because of the limitations of current staging systems and evolving definitions, there are limited data on oligometastatic non-small cell lung cancer (NSCLC) epidemiology. The purpose of this study was to evaluate metastatic disease burden and the incidence of oligometastatic disease using recent clinical trial eligibility criteria. A cohort of patients with metastatic NSCLC, diagnosed from 2016 to 2019, were randomly sampled from a curated tumor registry. Definitions for oligometastatic disease were obtained from relevant clinical trials. The Stanford Cancer Institute Research Database was used to identify baseline patient factors, systemic and local therapy, extent and location of metastatic lesions, and survival outcomes. Among 120 patients presenting with metastatic NSCLC, the majority had de novo metastatic disease (75%) with a median of 4 metastatic lesions involving 3 organ systems. Of these, 37.5% would have been eligible for at least 1 oligometastatic trial, with 28.3% meeting criteria for the MD Anderson Cancer Center trial, 20.0% for NRG-LU002, 6.7% for SINDAS, and 16.7% for SABR-COMET. By adding malignant pleural effusions and early progression as exclusionary criteria, only 54.1% of patients with ≤3 synchronous metastases were eligible for consideration of local therapy. Early progression on systemic therapy was associated with worse survival (10.0 vs 42.4 months; P < .001), whereas presence of malignant pleural effusions was not. Of those tumors identified as oligometastatic, 44.4% received local therapy and 28.9% underwent ablative therapy to all sites. There was a trend toward greater overall survival (44.4 vs 24.9 months; P=.055) and progression-free survival (8.0 vs 5.4 months; P=.06) in patients meeting eligibility for at least 1 oligometastatic trial. Around 48% of patients with metastatic NSCLC had ≤3 metastases at presentation and 28% met clinical trial criteria for oligometastatic disease. Future research is needed to better define the oligometastatic state and identify patients most likely to benefit from local therapy.

QIM22-191: Expansion of Tobacco Cessation Treatment Within the Stanford Cancer Institute: 6-Month and 24-Month Outcomes

QIM22-191: Expansion of Tobacco Cessation Treatment Within the Stanford Cancer Institute: 6-Month and 24-Month Outcomes

Uncovering interpretable potential confounders in electronic medical records

Randomized clinical trials (RCT) are the gold standard for informing treatment decisions. Observational studies are often plagued by selection bias, and expert-selected covariates may insufficiently adjust for confounding. We explore how unstructured clinical text can be used to reduce selection bias and improve medical practice. We develop a framework based on natural language processing to uncover interpretable potential confounders from text. We validate our method by comparing the estimated hazard ratio (HR) with and without the confounders against established RCTs. We apply our method to four cohorts built from localized prostate and lung cancer datasets from the Stanford Cancer Institute and show that our method shifts the HR estimate towards the RCT results. The uncovered terms can also be interpreted by oncologists for clinical insights. We present this proof-of-concept study to enable more credible causal inference using observational data, uncover meaningful insights from clinical text, and inform high-stakes medical decisions.

Editorial introductions.

Editorial introductions.

Natural Language Processing to Identify Cancer Treatments With Electronic Medical Records.

Knowing the treatments administered to patients with cancer is important for treatment planning and correlating treatment patterns with outcomes for personalized medicine study. However, existing methods to identify treatments are often lacking. We develop a natural language processing approach with structured electronic medical records and unstructured clinical notes to identify the initial treatment administered to patients with cancer. We used a total number of 4,412 patients with 483,782 clinical notes from the Stanford Cancer Institute Research Database containing patients with nonmetastatic prostate, oropharynx, and esophagus cancer. We trained treatment identification models for each cancer type separately and compared performance of using only structured, only unstructured (bag-of-words, doc2vec, fasttext), and combinations of both (structured + bow, structured + doc2vec, structured + fasttext). We optimized the identification model among five machine learning methods (logistic regression, multilayer perceptrons, random forest, support vector machines, and stochastic gradient boosting). The treatment information recorded in the cancer registry is the gold standard and compares our methods to an identification baseline with billing codes. For prostate cancer, we achieved an f1-score of 0.99 (95% CI, 0.97 to 1.00) for radiation and 1.00 (95% CI, 0.99 to 1.00) for surgery using structured + doc2vec. For oropharynx cancer, we achieved an f1-score of 0.78 (95% CI, 0.58 to 0.93) for chemoradiation and 0.83 (95% CI, 0.69 to 0.95) for surgery using doc2vec. For esophagus cancer, we achieved an f1-score of 1.0 (95% CI, 1.0 to 1.0) for both chemoradiation and surgery using all combinations of structured and unstructured data. We found that employing the free-text clinical notes outperforms using the billing codes or only structured data for all three cancer types. Our results show that treatment identification using free-text clinical notes greatly improves upon the performance using billing codes and simple structured data. The approach can be used for treatment cohort identification and adapted for longitudinal cancer treatment identification.

Heterogeneous Definitions of Secondary Acute Myeloid Leukemia (AML) Yield Distinct Outcomes in Response to First-Line Treatment with Hypomethylating Agents (HMA) and Venetoclax (Ven)

Background:The combination of HMA and venetoclax is now standard of care for patients with AML who are not candidates for intensive chemotherapy. Elderly patients are more likely to have secondary AML (sAML), although the presence of an antecedent hematologic malignancy is often not apparent by history. Lindsley et al (Blood, 2015) showed that a somatic mutation in SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 is >95% specific for sAML and associated with worse outcomes. While outcomes with HMA/ven in patients meeting standard criteria for sAML have recently been reported (Pullarkat, ASCO 2021), we set out to conduct a real-world analysis of sAML patients receiving HMA/ven, including those with a secondary mutation profile (SMP) as described by Lindsley et al. We hypothesized that-when treated with HMA/ven-outcomes of patients with SMP may be most similar to those with de novo AML.Methods:Patients diagnosed with AML at Stanford Cancer Institute from 4/2017-3/2021 and treated with front-line HMA/ven were retrospectively reviewed. These included patients previously treated with HMA monotherapy for an antecedent hematologic malignancy and those who had previously received ≤ 3 cycles of HMA monotherapy for AML. Responses were classified per the modified International Working Group response criteria. Overall survival (OS) was assessed for all patients, and for patients who had a complete response (CR) or CR with incomplete hematologic recovery (CRi), duration of response (DoR) was also assessed. Statistical analyses were performed in R using the logrank test, with hazard ratios (HR) computed using the Cox proportional hazards model. For multivariate analyses, p-values for a specific variable were calculated using Cox proportional hazards regression.Results:82 patients met criteria for inclusion; 78 had valid response assessments and 49 (62.8%) had achieved a CR or CRi at first response assessment. Median age was 72 years, with 3 patients younger than 60. 62 patients were male, median ECOG performance status (PS) was 1, median Charlson Comorbidity Index (CCI) was 6, median time to death or end of follow-up from the start of treatment was 366 days, and 58% of patients had adverse risk AML per ELN guidelines. Fig 1a demonstrates demographics for de novo, sAML (excluding SMP), and patients with SMP AML. 13 patients met criteria for AML-MRC, 23 patients had prior history of antecedent hematologic malignancy (18 with MDS or CMML, 5 with MDS/MPN overlap or MPN), 12 had tAML, and 20 patients possessed a SMP and did not meet criteria for the other three categories of sAML. 14 patients with de novo AML were characterized by the absence of any of the above factors. Patients with de novo AML were less likely to have adverse risk disease (29% vs. 64% in others) and had lower CCI scores (mean 5.1 vs. 6.2) but had no significant differences in age, gender, follow-up time, or PS.There was no statistically significant difference in rates of CR/CRi between the different subgroups or the different types of sAML; 69% of patients with de novo AML, 79% of SMP patients, and 57% of patients with other types of sAML achieved a CR or CRi. However, SMP patients had response durations and OS patterns similar to patients with de novo AML (Fig 1b and 1c), and when grouped with de novo patients, both DoR (HR = 3.5, p = 0.047, Fig 1d) and OS (HR = 2.1, p = 0.042, Fig 1e) were significantly longer than those of the sAML patients. Neither DoR nor OS were significantly longer when the SMP patients were grouped with sAML patients (respectively: HR = 3.3, p = 0.22, Fig 1f; HR = 1.5, p = 0.37, Fig 1g). In multivariate Cox proportional regression adjusting for age, ELN risk category, CCI, and PS, worse OS for sAML patients was maintained relative to the SMP and de novo patients (HR 2.9, p = 0.036), although the difference in DoR was no longer significant (HR 4.4, p= 0.10).Conclusions:Patients meeting standard definitions of sAML had worse outcomes than those with de novo AML when treated with HMA/ven in a retrospective, real-world analysis. Although a secondary mutation profile as described by Lindsley et al may be helpful in identifying patients with sAML, when treated with HMA/ven, patients with this profile have outcomes that align more closely with those of patients with de novo AML. [Display omitted] DisclosuresMannis: Astex, Forty Seven Inc/Gilead, Glycomimetics, and Jazz Pharmaceuticals: Research Funding; AbbVie, Agios, Astellas Pharma, Bristol Myers Squibb, Genentech, MacroGenics, Pfizer, and Stemline: Consultancy.

Fixed Duration Combination Therapy with Ibrutinib (ibr) and Venetoclax (ven) Leads to Deep Responses in Relapsed/Refractory (rel/ref) Chronic Lymphocytic Leukemia (CLL): Results of a Phase 2 Study

Fixed Duration Combination Therapy with Ibrutinib (ibr) and Venetoclax (ven) Leads to Deep Responses in Relapsed/Refractory (rel/ref) Chronic Lymphocytic Leukemia (CLL): Results of a Phase 2 Study

Association of treatment type with patient-reported quality of life in cancer distress screening.

178 Background: Routine distress screening is recommended for all patients with cancer. In 2015, Stanford Cancer Center implemented such screening using a modified PROMIS-GH questionnaire. With the recent growth of oncology drugs, novel medications have been perceived as better tolerated than chemotherapy. We analyzed patient reported quality of life with global mental health (GMH) and global physical health (GPH) scores for different medication classes. Methods: Patients who completed a questionnaire at our center between 6/1/2015 and 12/31/2020 were included. Medications were classified as chemotherapy, targeted therapy, endocrine therapy, or immunotherapy using guidance from SEER.Rx ontology. Baseline (B) and treatment (Tx) questionnaires were completed before any treatment initiation of each medication type and within 3 months of each treatment, respectively. GPH and GMH scores were calculated using PROMIS T-scores stratified by medication type for B and Tx questionnaires. We analyzed for differences based on demographics and diagnoses. Clinically significant differences were defined as a 3-point difference in T-scores, which then prompted statistical comparison with t-tests to compare the B and Tx scores to each other and to the US population mean of 50. Results: We analyzed 28,180 questionnaires from 11,644 patients (59% women, median age 64; 23% stage I and II, 12% stage III, 23% stage IV, 51% missing). B and Tx mean GMH scores did not differ clinically compared to the US mean or to each other (baseline: 49.03 +/- 9.16, post: 48.5 +/- 9.1). However, both mean GPH scores were statistically and clinically lower (baseline: 44.2+/- 10.38, post: 42.4 +/- 10.1,) compared to the US mean (p &lt; 0.001). Changes in scores by treatment category are shown in the table below. There was a statistically significant difference in post-treatment GPH scores for chemo-immunotherapy patients when compared to both corresponding baseline scores (p &lt; 0.001) and post treatment chemotherapy alone scores (p &lt; 0.001). There was no clinically significant difference in scores when stratified by age, sex, primary language, insurance, disease stage or type. Conclusions: In this large retrospective study, we found that patients being treated for cancer did not report worse GMH scores compared to the US mean population, but do report lower GPH scores. While most scores varied little relative to other treatment types, those receiving chemo-immunotherapy had lower GPH scores when comparing baseline to treatment and to the US mean, warranting further investigation, given increasing use.[Table: see text]

Association of telemedicine use with disparities in cancer distress screening for patients with limited English proficiency.

147 Background: Distress has a significant impact on the quality of life for patients with cancer, however, implementation of such screening is variable. There is limited data in this area for patients who have limited English proficiency (LEP). Given data suggesting worsening disparities in medical care with telemedicine use, we evaluated the completion of distress screening and interpreter use for LEP patients with telemedicine. Methods: We analyzed assigned (complete and incomplete) questionnaires from 10/2019-3/2021 at Stanford Cancer Center (n = 181,105). We defined LEP as a patient electronic health record (EHR) demographic listing either a non-English preferred language or a request for an interpreter. We defined telemedicine as any video or phone visit. Data was analyzed with Fisher's test for differences. Given limitations in EHR data, we conducted a validation subset chart review for LEP patients in Thoracic and Gastrointestinal (GI) oncology which have the two highest % of LEP patients (n = 177 patients). The subset list was obtained for the above timeframe from the interpreter services group. We analyzed EHR notes from visit day for written mention of professional vs family interpreter use. Results: Overall, 14% of our cohort had LEP, highest prevalence in the Thoracic (21%) and GI groups (16%), with a total of 48 languages represented (Spanish, Mandarin &amp; Vietnamese as the 3 most common). There was a significant difference in the English and Non-English groups in overall completion rates of the screening questionnaire (62% in English population vs 49% for LEP, p &lt; 0.001). Completion rates for telemedicine vs. in person visits were overall higher for both English (78.9% vs. 55%, p &lt; 0.001) and LEP (65.1% vs. 43.7%, p &lt; 0.001) groups respectively. The overall screening completion rate for all visits was 57%, with a 62% completion rate with telemedicine and 51% completion with in-person visits (p = 0.2). In the LEP validation subset, there were 18 languages represented with the similar distribution as the larger cohort. Of all clinical notes reviewed, 48.8% included written mention of professional interpreter use, while 25.5% noted interpretation by a family member. There was no difference in professional interpreter use between visit types (̃50%), but with higher rate of family interpretation with telemedicine (35%) vs with in person visits (21%) (p = 0.04). Conclusions: Patients who have some level of limited English proficiency complete distress screening questionnaires less frequently compared to English speaking patients, which highlights the need to improve access to distress screening and supportive care. However, we found similar completion rates with in person vs telemedicine visits, with a signal for increased use of family members as interpreter with telemedicine. This warrants further analysis of the family role and patient understanding during these virtual visits.

Coaches Activating Reaching and Engaging Patients (CAREPlan): A randomized controlled trial combining two evidence-based interventions to improve goals of care documentation.

2 Background: In our prior work, community or lay health worker-led goals of care interventions improved goals of care documentation by clinicians and decreased health care use at the end of life. Other studies have demonstrated improvements in provider-patient communication and goals of care documentation using the Serious Illness Care Program. The objective of this study was to determine whether the combination of these two interventions could improve goals of care documentation among patients with advanced stages of genitourinary cancers at an academic center. Methods: A randomized controlled trial was conducted from April 3, 2019, through October 30, 2019, among patients with metastatic or recurrent cancer on at least second line therapy in the urologic oncology clinics at Stanford Cancer Center. Patients were randomized to usual care or the intervention with a lay navigator trained to assist patients with establishing end-of-life care preferences using the Serious Illness Conversation Guide. The primary outcome was goals of care documentation by the primary oncologist. We used intent to treat analyses, descriptive statistics to compare demographic and clinical factors, and a logistic regression adjusting for imbalance to determine the effect on the primary outcome. Results: Two-hundred participants were randomized and included in the intent to treat analysis. Median age was 72 years, majority were male (n=175, 87.5%) and self-identified as non-Hispanic white (n=123, 61.5%). The majority had prostate cancer (n=110, 53.5%), followed by kidney cancer (n=51, 25.5%), and urothelial cancer (n=29, 14.5%) and most had stage IV disease at diagnosis (n=186, 93%). There were no significant differences in demographic or clinical factors except for gender; there were more females on the control arm (n=8 vs n=17, p=0.01) thus analysis of the primary outcome was adjusted for gender. The adjusted analysis showed that at 12 months post-enrollment, the intervention significantly increased goals of care documentation by the primary oncologist as compared to the control group (53.7% vs 32.6%, p=0.002). Conclusions: The CAREPlan program increased goals of care documentation by the primary oncologist at this single academic medical center. Clinical trial information: NCT03856463.

Implementation of a cloud-based electronic patient-reported outcome (ePRO) platform in patients with advanced cancer

BackgroundPatient reported outcomes (PROs) have been associated with improved symptom management and quality of life in patients with cancer. However, the implementation of PROs in an academic clinical practice has not been thoroughly described. Here we report on the execution, feasibility and healthcare utilization outcomes of an electronic PRO (ePRO) application for cancer patients at an academic medical center.MethodsWe conducted a randomized trial comparing an experimental ePRO arm to standard of care in patients with advanced cancer in the thoracic, gastrointestinal, and genitourinary oncology groups at Stanford Cancer Center from March 2018 to November 2019. We describe the pre-implementation, implementation, and post-implementation phases of the ePRO arm, technological barriers, electronic health record (EHR) integration, clinician burden, and patient data privacy and security. Feasibility was pre-specified to be at least 70% completion of all questionnaires. Acceptability was based on patient and clinician feedback. Ambulatory healthcare utilization was assessed by reviewing numbers of phone messages, electronic portal messages, and referrals for supportive care.ResultsOf 617 ePRO questionnaires sent to 72 patients, 445 (72%) were completed. Most clinicians (87.5%) and patients (93%) felt neutral or positive about the ePRO tool’s ease of use. Exposure to ePRO did not cause a measurable change in ambulatory healthcare utilization, with a median of less than two phone messages and supportive care referrals, and 5–6 portal messages.ConclusionsWeb-based ePRO tools for patients with advanced cancer are feasible and acceptable without increasing clinical burden. Key lessons include the importance of pilot testing, engagement of stakeholders at all levels, and the need for customization by disease group. Future directions for this work include completion of EHR integration, expansion to other centers, and development of integrated workflows for routine clinical practice.