Changes in Multiple Myeloma Treatment Patterns during the Early COVID-19 Pandemic Period

Background: Early during the COVID-19 pandemic patient and provider anxiety concerning in-person visits and travel restrictions may have delayed cancer diagnosis and altered treatment. We evaluated changes in clinical presentation and treatment patterns in multiple myeloma (MM) during the early COVID-19 period compared to historical pre-COVID periods. Methods: Using the nationwide Flatiron Health EHR-derived de-identified database, we compared clinical presentation and treatment patterns in the immediate post-COVID period (2020) to a comparable pre-COVID period (2018 and 2019). We focused on two separate clinical settings: 1) patients newly diagnosed with MM during February-June in the years of interest (NEWPT) with evidence of management within 90 days and follow-up for 7 months; and 2) patients diagnosed with MM during 2014-2019 receiving active treatment as of February (2018, 2019, 2020, ACTIVE) and follow-up for 11 months. Delayed clinical presentation was assessed using baseline (90 days before diagnosis/index date) measures of ISS stage, ECOG performance status, anemia, and kidney function. We examined treatment patterns (choice of regimen) of both cohorts in the two time periods. We compared clinical features of initial presentation in pre-COVID and COVID period using Pearson's χ 2 test. For NEWPT, we also utilized Kaplan-Meier curves and log-rank test to compare time to treatment initiation between the two periods. Multivariable Cox proportional hazards regression model with death as a competing risk was used to determine impact of COVID on treatment initiation by adjusting sex, age at diagnosis, race, insurance, stage, baseline ECOG, and hospital setting. All analyses were conducted in SAS (Version 9.4, SAS Institute, Cary, North Carolina) with 2 sided tests and a type I error of 5%. Results: Our study included 1319 NEWPT (964 pre-COVID and 355 COVID) and 2206 ACTIVE (1014 pre-COVID and 1192 COVID) patients. In the NEWPT cohort, we observed no differences between the pre-COVID and COVID periods in terms of baseline characteristics, including clinical features like stage, ECOG performance status, anemia or kidney function (Table A). Patients in the pre-COVID period were more likely to initiate any treatment (91.1% vs 86.2%, p<.01). Median time to treatment initiation was 30 days pre-Covid and 32 days during the Covid period (log-rank test p=0.04, Figure A). After adjusting for patient demographic, clinical features (extent of anemia, hypercalcemia, kidney dysfunction), and hospital variables (US region, practice type academic vs community), the difference between the two periods was not significant (COVID vs pre-COVID hazard ratio=0.88, 95% confidence interval 0.78-1.10, p=0.07). In NEWPT cohort, compared with their pre-COVID counterparts, patients in COVID period were more likely to receive monoclonal antibody (mAb) (14.4% vs 4.8%, p<.01, Figure B) and used IMID-based regimen as their first line of therapy (80.4% vs 74.3%, p<.01). In ACTIVE cohort, more patients in the pre-COVID period were anemic (Hemoglobin <10 g/L, 14.9% vs 9.7%, p<.01) at baseline than those in the COVID period. As in NEWPT cohort, ACTIVE patients in the COVID period used mAb-based regimen more commonly (28.9% vs 16.9%, p<.01) (Figure C). In addition, fewer ACTIVE treatment patients in the COVID period received cyclophosphamide regimens (7.9% vs 15.1% p<.01). Conclusions: During early COVID-19 pandemic we did not observe evidence of delayed diagnosis or more advanced stage, anemia or kidney disease for NEWPT with MM. MM treatment patterns were notable for higher utilization of mAb, IMID-based therapies and decreased use of cyclophosphamide regimens, without significant change in time to treatment initiation. Reassuringly, changes in treatment-patterns during COVID pandemic were modest, some likely reflecting changes in MM treatment landscape (advances in mAb regimens) rather than direct impact of COVID. Further studies are needed to understand how these changes evolve and affect clinical outcomes over time beyond 2020. Figure 1 Figure 1. Disclosures Neparidze: GlaxoSmithKline: Research Funding; Eidos Therapeutics: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding. Zeidan: Jasper: Consultancy; AstraZeneca: Consultancy; Aprea: Consultancy, Research Funding; Gilead: Consultancy, Other: Clinical Trial Committees; Loxo Oncology: Consultancy, Other: Clinical Trial Committees; Astellas: Consultancy; Agios: Consultancy; Kura: Consultancy, Other: Clinical Trial Committees; Jazz: Consultancy; Pfizer: Other: Travel support, Research Funding; Genentech: Consultancy; Geron: Other: Clinical Trial Committees; BMS: Consultancy, Other: Clinical Trial Committees, Research Funding; ADC Therapeutics: Research Funding; Novartis: Consultancy, Other: Clinical Trial Committees, Travel support, Research Funding; Boehringer Ingelheim: Consultancy, Research Funding; Astex: Research Funding; BeyondSpring: Consultancy; Incyte: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; Epizyme: Consultancy; BioCryst: Other: Clinical Trial Committees; Cardiff Oncology: Consultancy, Other: Travel support, Research Funding; Janssen: Consultancy; Ionis: Consultancy; Amgen: Consultancy, Research Funding; Acceleron: Consultancy, Research Funding; AbbVie: Consultancy, Other: Clinical Trial Committees, Research Funding. Podoltsev: Pfizer: Honoraria; PharmaEssentia: Honoraria; Blueprint Medicines: Honoraria; Incyte: Honoraria; Novartis: Honoraria; CTI BioPharma: Honoraria; Bristol-Myers Squib: Honoraria; Celgene: Honoraria. Shallis: Curis: Divested equity in a private or publicly-traded company in the past 24 months. Ma: Celgene/Bristol Myers Squibb: Consultancy, Research Funding. Davidoff: Amgen: Consultancy; AbbVie: Other: Family member consultancy. Huntington: AstraZeneca: Consultancy, Honoraria; TG Therapeutics: Research Funding; Thyme Inc: Consultancy; Flatiron Health Inc.: Consultancy; Genentech: Consultancy; SeaGen: Consultancy; Novartis: Consultancy; Pharmacyclics: Consultancy, Honoraria; Servier: Consultancy; Bayer: Honoraria; DTRM Biopharm: Research Funding; AbbVie: Consultancy; Celgene: Consultancy, Research Funding.

Impact of telemedicine adoption on accessibility and time to treatment in patients with thoracic malignancies during the COVID-19 pandemic

Background To ensure safe delivery of oncologic care during the COVID-19 pandemic, telemedicine has been rapidly adopted. However, little data exist on the impact of telemedicine on quality and accessibility of oncologic care. This study assessed whether conducting an office visit for thoracic oncology patients via telemedicine affected time to treatment initiation and accessibility. Methods This was a retrospective cohort study of patients with thoracic malignancies seen by a multidisciplinary team during the first surge of COVID-19 cases in Philadelphia (March 1 to June 30, 2020). Patients with an index visit for a new phase of care, defined as a new diagnosis, local recurrence, or newly discovered metastatic disease, were included. Results 240 distinct patients with thoracic malignancies were seen: 132 patients (55.0%) were seen initially in-person vs 108 (45.0%) via telemedicine. The majority of visits were for a diagnosis of a new thoracic cancer (87.5%). Among newly diagnosed patients referred to the thoracic oncology team, the median time from referral to initial visit was significantly shorter amongst the patients seen via telemedicine vs. in-person (median 5.0 vs. 6.5 days, p < 0.001). Patients received surgery (32.5%), radiation (24.2%), or systemic therapy (30.4%). Time from initial visit to treatment initiation by modality did not differ by telemedicine vs in-person: surgery (22 vs 16 days, p = 0.47), radiation (27.5 vs 27.5 days, p = 0.86, systemic therapy (15 vs 13 days, p = 0.45). Conclusions Rapid adoption of telemedicine allowed timely delivery of oncologic care during the initial surge of the COVID19 pandemic by a thoracic oncology multi-disciplinary clinic.

Analysis of racial disparities in time to treatment initiation and survival among patients with advanced cancers.

127 Background: Racial disparities in cancer care have received increased attention in recent years. One previously identified disparity is in the time to treatment initiation (TTI) – a factor closely associated with outcomes. While most research in the US to date has focused on the Medicaid and Medicare populations, this study examined disparities between different racial/ethnic groups in TTI and overall survival (OS) among patients with cancer managed in the community setting. Methods: Using the Flatiron Health electronic health record database, patients diagnosed with advanced non-small cell lung cancer (aNSCLC), metastatic colorectal cancer (mCRC), metastatic breast cancer (mBC), multiple myeloma (MM), advanced gastroesophageal cancer (aGastric), advanced urothelial cancer (aUL), metastatic renal cell carcinoma (mRCC) or advanced melanoma (aMel) and treated with first-line (1L) therapy, with ≥1 month of follow-up during 2014-2019, were included. Patient characteristics, TTI and outcomes were compared across race/ethnicity groups classified as White, Black, Asian and Hispanic/Latino/Other (Other). Results: A total of 81,543 patients were evaluated (37% aNSCLC, 19% mCRC, 15% mBC, 8% MM, 6% aGastric, 5.2% aUL, 5.0% mRCC and 4.1% aMel); 67% were White, 9% Black, 3% Asian and 11% Other. Overall, TTI was similar across race/ethnicity groups (median range 1.1–1.2 months), and 44% of all patients received treatment ≤30 days post-diagnosis. Overall Survival (months). Median OS varied by tumor and race/ethnicity groups (Table). However, multivariate Cox proportional hazards analysis showed that Asian patients had better OS than Black patients in many cancers (hazard ratio [HR] 0.8 aNSCLC, 0.75 mBC, 0.63 aGastric, 0.59 aUL, 0.81 mCRC, 0.68 mRCC), while White patients had better survival than Black patients in mBC (HR 0.8) and aGastric (HR 0.87). Conclusions: In this real-word analysis, TTI did not differ by race/ethnicity group for any of the cancers examined. However, some differences in OS emerged on multivariate analysis – this was longer in Asian than Black patients in aNSCLC, mBC, mCRC, aGastric, aUL and mRCC, and longer in White than Black patients in mBC and aGastric. Given the small sample size in some groups, further analyses are needed to determine the influence of race/ethnicity on cancer care and outcomes.[Table: see text]

Impact of the COVID-19 pandemic on treatment patterns for US patients with metastatic solid cancer

Background: The COVID-19 pandemic has led to delays in patients seeking care for life-threatening conditions; however, its impact on treatment patterns for patients with metastatic cancer is unknown. We assessed the impact of the COVID-19 pandemic on time to treatment initiation (TTI) and treatment selection for patients newly diagnosed with metastatic solid cancer. Methods: We used an electronic health record-derived longitudinal database curated via technology-enabled abstraction to identify 14,136 US patients newly diagnosed with de novo or recurrent metastatic solid cancer between January 1 and July 31 in 2019 or 2020. Patients received care at ~280 predominantly community-based oncology practices. Controlled interrupted time series analyses assessed the impact of the COVID-19 pandemic period (April-July 2020) on TTI, defined as the number of days from metastatic diagnosis to receipt of first-line systemic therapy, and use of myelosuppressive therapy. Results: The adjusted probability of treatment within 30 days of diagnosis [95% confidence interval] was similar across periods: January-March 2019 41.7% [32.2%, 51.1%]; April-July 2019 42.6% [32.4%, 52.7%]; January-March 2020 44.5% [30.4%, 58.6%]; April-July 2020 46.8% [34.6%, 59.0%]; adjusted percentage-point difference-in-differences 1.4% [-2.7%, 5.5%]. Among 5,962 patients who received first-line systemic therapy, there was no association between the pandemic period and use of myelosuppressive therapy (adjusted percentage-point difference-in-differences 1.6% [-2.6%, 5.8%]). There was no meaningful effect modification by cancer type, race, or age. Conclusions: Despite known pandemic-related delays in surveillance and diagnosis, the COVID-19 pandemic did not impact time to treatment initiation or treatment selection for patients with metastatic solid cancers.

193 Evaluation of the ‘One-Stop Diagnostic Head and Neck Lump Clinic' At A Tertiary Head and Neck Centre

An urgent neck lump service was introduced at the Freeman Hospital (Newcastle-Upon-Tyne) in 2017. All 2-week-wait urgent head and neck referrals were triaged into this service. The clinic involves clinical examination by a head and neck specialist and if appropriate an urgent ultrasound scan (USS) in clinic +/- a fine needle aspiration for cytology (FNAC). This centralised system means patients can be diagnosed earlier and thus receive treatment swiftly. This audit aimed to primarily identify: The prevalence/pick-up rate of cancer diagnosed through the clinic The utilisation of USS/FNAC The time-to-treatment initiation Data was collated retrospectively through the electronic record system. The initial evaluation was conducted between June-November 2018 (n = 191). The subsequent re-evaluation was performed between September-November 2019 (n = 159), following increased clinic capacity, implementation of methods to increase awareness and a formal triage process. In the initial evaluation over 6 months (n = 191), 9.9% underwent an USS in the clinic and 9.95% at a later date. 18% of patients underwent a FNAC. 6.8% patients were diagnosed with cancer. The mean time-to-treatment initiation was 36 days. In the re-evaluation over 3 months (n = 159), 23.2% had an USS in the clinic and 30.2% at a later date. 13% of patients underwent a FNAC. 9.4% of patients were diagnosed with cancer. The mean time-to-treatment initiation was 44 days. This affirms the benefits of a swift ‘one-stop clinic’. On average, patients diagnosed with cancer had treatment initiation 40-days post-review. Furthermore, even with a triage process only 1 in 10 patients had cancer.

Integrated treatment of hepatitis C virus infection among people who inject drugs: A multicenter randomized controlled trial (INTRO-HCV)

Background The standard pathways of testing and treatment for hepatitis C virus (HCV) infection in tertiary healthcare are not easily accessed by people who inject drugs (PWID). The aim of this study was to evaluate the efficacy of integrated treatment of chronic HCV infection among PWID. Methods and findings INTRO-HCV is a multicenter, randomized controlled clinical trial. Participants recruited from opioid agonist therapy (OAT) and community care clinics in Norway over 2017 to 2019 were randomly 1:1 assigned to the 2 treatment approaches. Integrated treatment was delivered by multidisciplinary teams at opioid agonist treatment clinics or community care centers (CCCs) for people with substance use disorders. This included on-site testing for HCV, liver fibrosis assessment, counseling, treatment, and posttreatment follow-up. Standard treatment was delivered in hospital outpatient clinics. Oral direct-acting antiviral (DAA) medications were administered in both arms. The study was not completely blinded. The primary outcomes were time-to-treatment initiation and sustained virologic response (SVR), defined as undetectable HCV RNA 12 weeks after treatment completion, analyzed with intention to treat, and presented as hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals. Among 298 included participants, 150 were randomized to standard treatment, of which 116/150 (77%) initiated treatment, with 108/150 (72%) initiating within 1 year of referral. Among those 148 randomized to integrated care, 145/148 (98%) initiated treatment, with 141/148 (95%) initiating within 1 year of referral. The HR for the time to initiating treatment in the integrated arm was 2.2 (1.7 to 2.9) compared to standard treatment. SVR was confirmed in 123 (85% of initiated/83% of all) for integrated treatment compared to 96 (83% of initiated/64% of all) for the standard treatment (OR among treated: 1.5 [0.8 to 2.9], among all: 2.8 [1.6 to 4.8]). No severe adverse events were linked to the treatment. Conclusions Integrated treatment for HCV in PWID was superior to standard treatment in terms of time-to-treatment initiation, and subsequently, more people achieved SVR. Among those who initiated treatment, the SVR rates were comparable. Scaling up of integrated treatment models could be an important tool for elimination of HCV. Trial registration ClinicalTrials.gov.no NCT03155906

Patients with an increased time to treatment initiation have a poorer overall survival after definitive surgery for localized high-grade soft-tissue sarcoma in the extremity or trunk

Aims Time to treatment initiation (TTI) is generally defined as the time from the histological diagnosis of malignancy to the initiation of first definitive treatment. There is no consensus on the impact of TTI on the overall survival in patients with a soft-tissue sarcoma. The purpose of this study was to determine if an increased TTI is associated with overall survival in patients with a soft-tissue sarcoma, and to identify the factors associated with a prolonged TTI. Methods We identified 23,786 patients from the National Cancer Database who had undergone definitive surgery between 2004 and 2015 for a localized high-grade soft-tissue sarcoma of the limbs or trunk. A Cox proportional hazards model was used to examine the relationship between a number of factors and overall survival. We calculated the incidence rate ratio (IRR) using negative binomial regression models to identify the factors that affected TTI. Results Patients in whom the time to treatment initiation was prolonged had poorer overall survival than those with a TTI of 0 to 30 days. These were: 31 to 60 days (hazard ratio (HR) 1.08, p = 0.011); 61 to 90 days (HR 1.11, p = 0.044); and 91 days (HR 1.22; p = 0.003). The restricted cubic spline showed that the hazard ratio increased substantially with a TTI longer than 50 days. Non-academic centres (vs academic centres; IRR ranging from 0.64 to 0.86; p < 0.001) had a shorter TTI. Those insured by Medicaid (vs private insurance; IRR 1.34), were uninsured (vs private insurance; IRR 1.17), or underwent a transition in care (IRR 1.62) had a longer TTI. Conclusion A time to treatment initiation of more than 30 days after diagnosis was independently associated with poorer survival. The hazard ratio showed linear increase, especially if the TTI was more than 50 days. We recommend starting treatment within 30 days of diagnosis to achieve the highest likelihood of cure for localized high-grade soft-tissue sarcomas in the limbs and trunk, even when a patient needs to be referred to a specialist centre. Cite this article: Bone Joint J 2021;103-B(6):1142–1149.

Impact of time to treatment initiation on real-world (RW) outcomes in metastatic pancreatic cancer (mPC) in the United States.

e16254 Background: The COVID-19 pandemic caused disruptions in cancer care delivery and forced oncologists to make recommendations about safely delaying initiation of cancer therapy. Compared to the adjuvant, curative setting, there is a scarcity of information about the impact of time to treatment initiation on outcomes in the palliative setting for gastrointestinal malignancies. We sought to determine the median time to initiation of systemic therapy (TIT) in mPC in the US pre-pandemic, and to assess the impact of TIT on survival outcomes. Methods: We retrospectively analyzed de-identified data of patients with mPC in the Flatiron Health nationwide EHR-derived database. Metastatic diagnosis dates between 01/2014 and 04/2020 were included. Demographics, treatments, and outcomes were collected. TIT was defined as period between diagnosis and initiation of first-line systemic therapy and was split into 3 categories (I: < 2 weeks, II: 2- <4 weeks, and III: 4-8 weeks). Overall survival (OS) was defined from time of diagnosis to time of death. Post-chemotherapy survival (PCS) was time from initiation of first-line therapy to death. Adjusted and unadjusted multinomial logistic regression were used to evaluate the association of demographics and clinical factors with TIT. PCS and OS were estimated with Kaplan-Meier curves. Adjusted (demographics and clinical factors) Cox proportional hazard models were used to estimate the effect of TIT groups on PCS and OS. Category II served as control group. Results: 3231 patients with mPC who received at least one line of treatment were identified. 29% (N= 947), 43% (N=1375), and 28% (N= 909) were in TIT categories I-III respectively. The mean age at diagnosis was 67.4 years, with no significant difference in age (P=0.14) among categories. Median TIT was 20 days. Multinomial logistic regression showed that compared to TIT II, Black patients were less likely than White patients to receive chemotherapy in less than 2 weeks (P=0.02), and those who had recurrent disease were more likely to receive therapy in less than 2 weeks (P< 0.0001). There was no significant difference in median RW OS among the groups (I: 8.13, II: 8.07, III: 9.02 months, P=0.0532). RW PCS was also similar across categories (I: 7.8, II: 7.5, III: 7.8 months, P=0.88). Adjusted cox regression analysis suggests that compared to TIT of 2-4 weeks, TIT 4-8 weeks was associated with higher RW OS (HR, 0.88, 95% CI 0.8-0.97, P=0.009), but not RW PCS (HR, 0.95, 95% CI 0.87-1.05, P=0.32). Conclusions: This real-world analysis suggests that pre-pandemic, most patients with mPC who receive 1st line therapy were treated within 4 weeks of diagnosis. Compared to TIT of 2-4 weeks, TIT 4-8 weeks was associated with higher RW OS in mPC, although the clinical significance is minimal. In crisis situations, efforts to clinically optimize patients with mPC before systemic therapy should continue to be pursued.

Impact of time to treatment initiation on real-world (RW) outcomes in metastatic colorectal cancer (mCRC) in the United States.

3595 Background: The COVID-19 pandemic caused disruptions in cancer care delivery and forced oncologists to make recommendations about safely delaying initiation of therapy. Compared to the adjuvant setting, information about the impact of time to treatment initiation on outcomes in the palliative setting for CRCis scarce. We sought to determine the median time to initiation of systemic therapy (TIT) in mCRC in the US pre-pandemic, and to assess the impact of TIT on survival outcomes. Methods: We retrospectively analyzed de-identified data of patients (pnts) with mCRC in the Flatiron Health nationwide EHR-derived database (metastatic diagnosis dates 01/2013 - 04/202000. Demographics, treatments (tx), and outcomes were collected. TIT, the period between diagnosis and initiation of first-line systemic therapy was split into 3 categories (I: < 2 weeks, II: 2- < 4 weeks, and III: 4-8 weeks). Overall survival (OS) was defined from time of diagnosis to time of death. Post-chemotherapy survival (PCS) was time from initiation of first-line therapy to death. Adjusted and unadjusted multinomial logistic regression were used to evaluate the association of demographics and clinical factors with TIT. PCS and OS were estimated using Kaplan-Meier curves. Adjusted (demographics and clinical factors) Cox proportional hazard models were used to estimate the effect of TIT groups on PCS and OS. Category II was control group. Results: 7,108 pnts with mCRC who received at least one line of tx were identified. 16% (N = 1132), 34% (N = 2406), and 50% (N = 3570) were in TIT categories I-III. The mean age at diagnosis was 63.4 years, with no significant difference in age (P = 0.6) among categories. Median TIT was 28 days. Multinomial logistic regression showed that compared to TIT II, Hispanic pnts were more likely than Whites to receive chemotherapy in 4-8 weeks (OR 1.4, 95% CI 1.12- 1.7, P= 0.0022). Females were more likely to receive treatment in 4-8 weeks (OR 1.14, 95% CI 1.03- 1.27, P= 0.01). Pnts without documented KRAS testing were more likely to receive tx within 2 weeks (OR 1.3, 95% CI 1.05- 1.48, P= 0.01). Median RW OS favored group III (I: 18.1, II: 22.6, III: 26.9, P< 0.0001). Adjusted Cox regression analysis suggested that Blacks had a higher hazard of death compared to Whites, (HR, 1.14. 95% CI 1.03 -1.27, P = 0.01) Also, compared to TIT of 2-4 weeks, TIT < 2 weeks was associated with lower RW PCS (HR, 1.22, 95% CI 1.11- 1.33, P= 0.0001), and RW OS (HR, 1.25, 95% CI 1.14- 1.37, P= <0.0001). In contrast, TIT 4-8 weeks was associated with higher RW PCS (HR, 0.81, 95% CI 0.75- 0.87, P= 0.0001) and RW OS (HR, 0.78, 95% CI 0.72- 0.83 P= <0.0001. Conclusions: This RW analysis suggests that pre-pandemic, 50% of patients with mCRC who receive first-line therapy were treated within 4 weeks of diagnosis. We observed disparities in TIT. Paradoxically, RW survival increased with TIT, with the best outcomes reported in those treated in 4-8 weeks.