Real-World Treatment Patterns and Outcomes of Patients with Chronic Lymphocytic Leukemia (CLL) Receiving First-Line (1L) Therapy in the United States (US)

Abstract Background: There have been many advances in CLL treatments over the past decade, with a number of novel agents targeting molecular pathways within CLL cells receiving approval from the US Food and Drug Administration. Here, we assessed the evolution of molecular testing patterns, treatment patterns, and clinical outcomes over time in patients receiving 1L CLL treatment in a real-world US database. Methods: This was a retrospective cohort study using the Flatiron Health database, a longitudinal database comprising de-identified, patient-level, structured and unstructured data, curated via technology-enabled abstraction. During the study period, the de-identified data originated from approximately 280 cancer clinics (~800 sites of care) in the US. Patients aged 18 years and older who were diagnosed with CLL and initiated 1L treatment between December 2015 and December 2020 were selected. Participants who took part in a clinical trial in any line of therapy, or who had any other primary cancer diagnosis, were excluded. Baseline characteristics, including testing patterns, at initiation of 1L treatment were assessed using descriptive statistics. Treatment patterns and outcomes, such as time to next treatment or death (TTNTD), were analyzed. Kaplan-Meier analysis was used to estimate TTNTD. Results: Among 3654 patients with treatment-naive CLL who were selected from the de-identified database, the mean age at 1L treatment initiation was 70 years (range, 29-85); 64.3% of patients were male; 72.1% were White, 8.2% Black, 3.9% Hispanic/Latino, 1.0% Asian, and 14.9% were of other ethnicity/race. Approximately one-third (34.7%) of patients had Rai stage 0-I disease, 6.9% had stage II, 6.3% stage III, 11.5% stage IV, and 40.6% had undocumented Rai stage. Testing patterns: The majority of identified patients (3202/3654; 87.6%) had undergone cytogenetic testing, fluorescence in situ hybridization, or IGHV mutation testing. Compared with 2015-2016, testing rates were higher in 2019-2020 for chromosome 17p deletion (del(17p); 36.1% vs 45.7%, respectively; p<0.001) and for IGHV mutation status (84.7% vs 89.2%, respectively; p=0.003). Overall, 11.0% of patients had del(17p). Of those tested for IGHV (1472/3654; 40.3%), 58.3% had unmutated IGHV. Treatment patterns: The 10 most commonly used 1L CLL treatments, which overall represented 91.8% of all 1L treatments, and their evolution over time, are reported in Table 1. Of the patients receiving these top 10 1L treatment regimens overall, 45.7% received regimens including novel targeted oral agents, 33.4% received chemo-immunotherapy (CIT), and 19.7% received anti-CD20 monotherapy. Evaluation of each 2-year period shows that treatment patterns for the top 10 1L treatment regimens shifted, with use of novel targeted oral agents increasing from 27.1% (2015-2016) to 63.8% (2019-2020) (p<0.001), while use of CIT and chemotherapy decreased over time (Table 2). Approximately 30.0% (1088/3654) of 1L-treated patients went on to receive second-line treatments. Outcomes: Median TTNTD was 34.4 months for all patients receiving 1L CLL treatment, and 36.5 months for patients who received the 10 most common 1L treatments across the 6-year study period (n=3360). Median TTNTD was 47.0 months for patients who received novel targeted oral agents and 41.5 months for patients who received CIT (unadjusted p=0.16). When evaluating outcomes in patients with high-risk cytogenetics, median TTNTD was 29.1 months for patients with del(17p) and 37.2 months for those with unmutated IGHV, but was longer in those patients who received treatment with novel targeted oral agents (median TTNTD of 43.9 and 46.7 months, respectively; Table 3). Conclusions: This analysis provides the current state of 1L CLL testing and treatment patterns and outcomes in the US from 2015 to 2020. As expected, the use of novel targeted oral agents increased over time, with a corresponding increase in TTNTD. Clinical outcomes were improved in patients receiving novel targeted oral agents, both overall and in high-risk subgroups. Following on from this, a comparative study of TTNTD for novel oral agents versus CIT, and analyses of outcomes of different sequencing of therapies, will be conducted. Figure 1 Figure 1. Disclosures Mato: Nurix: Research Funding; Johnson and Johnson: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Acerta/AstraZeneca: Consultancy, Research Funding; DTRM BioPharma: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; MSKCC: Current Employment; Sunesis: Consultancy, Research Funding; AstraZeneca: Consultancy; TG Therapeutics: Consultancy, Other: DSMB, Research Funding; Genmab: Research Funding; LOXO: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Ravelo: Genentech, Inc.: Current Employment; Roche Holdings: Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. To: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Schuldt: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Johnson & Johnson: Divested equity in a private or publicly-traded company in the past 24 months. Biondo: Genentech, Inc.: Current Employment; Roche: Current holder of individual stocks in a privately-held company.

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Treatment Patterns and Outcomes of Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) Treated with Hypomethylating Agents (HMA) in the United States (US)

Blood ◽

10.1182/blood-2020-134830 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 14-16

Author(s):

Timothy S. Pardee ◽

Jessica Oschwald ◽

Esprit Ma ◽

Tao Xu ◽

Melissa Montez ◽

...

Keyword(s):

Clinical Practice ◽

Research Funding ◽

Community Setting ◽

Patient Characteristics ◽

Treatment Patterns ◽

Survival Outcomes ◽

Newly Diagnosed ◽

Publicly Traded ◽

The Past ◽

The Us

Introduction: AML is an aggressive disease with poor prognosis that predominantly affects older adults. Due to advanced age and associated comorbidities, many patients are not fit for intensive induction chemotherapy. Monotherapy with HMAs such as azacitidine (AZA) or decitabine (DEC) is often still considered as standard of care for these patients, despite mixed evidence from studies regarding the benefit of HMAs alone (Duchmann & Itzykson. Int J Hematol 2019). The aim of the current study is to evaluate patient characteristics, treatment patterns and outcomes of patients with AML treated with HMA monotherapy as first line (1L) in clinical practice in the US. Methods: This is a retrospective observational study of the Flatiron Health database; a nationwide, longitudinal, demographically and geographically diverse database representing more than 2.4 million patients with cancer in the US. The database contains de-identified data derived from electronic health records from over 280 cancer clinics, which are predominantly community oncology practices. Patients ≥18 years, diagnosed with AML between 1/1/2014 and 3/30/2020 (excluding acute promyelocytic leukemia and clinical trial enrollment), and who received HMAs as 1L treatment ≤30 days from AML diagnosis were evaluated. Descriptive analyses were conducted on patient characteristics and treatment patterns. Kaplan-Meier analyses were used to estimate time to last administration (TTLA; from initiation to last observed administration before death, end of follow-up or a gap of 60 days) and median overall survival (OS). Results: A total of 2589 patients with an AML diagnosis were included for analysis, where 574 (22%) were treated with 1L HMAs (AZA: n=341 [59%]; DEC: n=233 [41%]). The median age of 1L HMA patients was 79 years with 63% male. Most patients were treated in the community setting (n=511 [89%]; median age: 79 years); those treated in academic centers were slightly younger (n=63 [11%]; median age: 77 years). Characteristics for non-antecedent hematological disorder (AHD)-AML (n=327) and AHD-AML (n=247) patients are presented in Table 1. Median TTLA with 1L HMA was 77 days with a median of 3 cycles of both AZA and DEC. Of the 168 patients who received second-line (2L) therapy, 82% (n=138) received another low-intensity therapy or combination (of which only 14 received targeted therapies) (Figure 1). Overall, 44% of 1L HMA patients (n=254) had evidence of molecular testing before 1L treatment initiation (this was more common in later years). Of the 228 patients tested for FLT3, 30 (13%) were FLT3 positive; 7 (23%) FLT3-positive patients were treated with 2L or third-line (3L) FLT3-targeted therapies (gilteritinib, midostaurin or sorafenib). Of the 152 patients tested for IDH1/2, 35 (23%) were IDH1/2 positive; 5 (14%) IDH1/2-positive patients were treated with 2L or 3L targeted agents (enasidenib or ivosidenib). A median OS of 6.3 months (95% CI: 5.5-7.5) was observed in the overall 1L HMA cohort. Median OS in 1L HMA patients did not differ with respect to different types of AML (non-AHD-AML: 6.6 [95% CI: 5.5-7.9] months; AHD-AML: 6.0 [95% CI: 4.8-7.5] months, p=0.34) or practice setting (community: 6.0 [95% CI: 5.3-7.0] months; academic: 8.3 [95% CI: 6.9-13.3] months, p=0.14). One-year OS was 31.4% and 30.1% for non-AHD-AML and AHD-AML patients, respectively. Patients treated in the community setting had numerically lower 1-year OS (29.7% [95% CI: 25.8-34.3]) than those treated in the academic setting (39.5% [95% CI: 28.6-54.6]), which reflects the higher rates of 2L treatment in academic practice, though this analysis is unadjusted. Conclusions: This new database enabled a detailed analysis of 1L HMA-treated patients with newly diagnosed AML in routine clinical practice predominantly in the community setting. 1L HMA patients have poor survival outcomes (median OS 6.3 months) which are comparable to other real-world data from SEER-Medicare (Zeidan et al. Blood Adv 2020; median OS 7-8 months; median age: 77 years); but shorter than the median OS of 9-10 months observed in 1L HMA-treated AML patients in clinical trials (DiNardo et al. EHA 2020). Limitations of the study included limited conduct of bone marrow biopsies for response and lack of transfusion data. The observed survival outcomes highlight the importance of further treatment advances to address the unmet need in older patients with AML ineligible for intensive induction chemotherapy. Disclosures Pardee: Rafael: Research Funding; Celgene: Consultancy, Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Pharmacyclics: Speakers Bureau; Rafael Pharmaceuticals: Consultancy; BMS: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy; Genentech, Inc.: Consultancy; Karyopharm: Research Funding. Oschwald:Roche Products Limited: Current Employment. Ma:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Xu:F. Hoffmann-La Roche Ltd: Current Employment, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Montez:F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Ramsingh:Genentech, Inc.: Current Employment; NEKTAR: Current equity holder in publicly-traded company; Exelixis: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Hong:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Choi:AbbVie: Current Employment, Current equity holder in publicly-traded company. Flahavan:Roche Products Ltd.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. OffLabel Disclosure: Discussion will include the use of decitabine for the treatment of AML.

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Hydroxyurea Treatment History and Quality of Life in Patients with Polycythemia Vera: Results from the MPN Landmark Survey in the United States

Blood ◽

10.1182/blood.v126.23.4077.4077 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4077-4077

Author(s):

Ruben A. Mesa ◽

Carole B. Miller ◽

John O. Mascarenhas ◽

Maureen Thyne ◽

Sara Goldberger ◽

...

Keyword(s):

High Risk ◽

Research Funding ◽

Symptom Burden ◽

Employment Equity ◽

Treatment History ◽

The Past ◽

Patient Reported ◽

The Us ◽

Equity Ownership

Abstract Background: Patients with the myeloproliferative neoplasm (MPN) polycythemia vera (PV) require treatment to manage blood cell counts and reduce the risks of cardiovascular/thromboembolic events. Hydroxyurea (HU) is a common cytoreductive treatment; however, some patients discontinue HU treatment because of resistance, intolerance, or frequently a combination of both limitations. Patients may also continue to receive HU despite diminishing or nonexistent clinical benefit, sometimes in combination with persistent need for phlebotomy procedures. This analysis of MPN Landmark survey data examined patient-reported quality of life (QoL) outcomes in patients with PV who were naive to HU (HU-N), were continuing HU (HU-C), or had discontinued HU (HU-D). Methods: Patients with an MPN under active management in the US were eligible to complete an online survey (fielded May - July 2014). This is a report of responses given by patients with PV to questions about symptom burden, QoL, activities of daily living (ADL), and work/productivity. PV-related effects on patients feeling depressed/discouraged, patients feeling anxious/worried, or interference with ADLs were considered to be at high levels if the patient-reported score was ≥4 on a scale of 1 (not at all) to 5 (a great deal). Symptom severity was rated on a scale of 0 (absent) to 10 (worst imaginable). Results: The survey respondents included 380 patients with PV (HU-N, n=159; HU-C, n=181; HU-D, n=40). Mean age was 62.2 years, 65.1 years, and 64.2 years in the HU-N, HU-C, and HU-D groups, respectively. Mean duration of PV was 8.3 years, 10.3 years, and 13.9 years in the HU-N, HU-C, and HU-D groups, respectively. Patients who had not received HU were currently or previously treated with phlebotomy (87.4%), interferon (11.3%), or anagrelide (9.4%); 66.0% of HU-N patients were classified as high-risk based on information provided by the patients in the survey (ie, age 60 or older or history of thrombosis). Among HU-C and HU-D patients, treatment history included phlebotomy (89.5% and 100%, respectively), interferon (7.2% and 52.5%), or anagrelide (15.5% and 35.0%); 79.6% and 82.5%, respectively, were classified as high-risk. Ruxolitinib was not FDA-approved for PV at the time of this survey. Patients reported high levels of feeling anxious/worried and depressed/discouraged as a result of their PV across all subgroups: HU-N, 27.7% and 15.1%, respectively; HU-C, 22.7% and 15.5%; HU-D, 32.5% and 22.5%. Many patients also experienced a high level of PV-related interference with ADLs, which was more common in the HU-D group (30.0%) than the HU-N (11.3%) or HU-C (18.2%) groups. HU-D patients were more likely to have reported ever reducing their work hours (54.2% of the patients who responded) compared with the HU-N (33.3%) and HU-C groups (36.8%). Among all patients, HU-D patients reported a mean of 8.3 doctor visits in the past 12 months, compared with 5.6 in the HU-N group and 6.6 in the HU-C group. Most patients had experienced PV-related symptoms in the past 12 months (Table 1), particularly fatigue, itching, and day/night sweats; fatigue was ranked first as the symptom that patients would most like to resolve. Conclusion: Patients with PV in a large retrospective real-world survey across the US are found to experience burdensome PV-related symptoms and reduced QoL. The findings from this study also show that standard treatments do not address these aspects of PV in many patients, and patients who have discontinued HU may experience an even greater disease burden, possibly because of a lack of effective and/or safe alternative treatment options. Importantly, while 66.0% of the patients in the HU-N group were classified as high-risk, the majority of the high-risk patients in the HU-N group (81.0%) were not treated with cytoreductive agents, suggesting a potential knowledge deficit regarding recommendations for PV management. Collectively, these results illustrate the adverse impact of PV-related symptom burden on patient QoL and reinforce the importance of unmet control of PV-related symptoms in choosing PV therapy. Disclosures Mesa: Novartis Pharmaceuticals Corporation: Consultancy; NS Pharma: Research Funding; Pfizer: Research Funding; Genentech: Research Funding; CTI Biopharma: Research Funding; Incyte Corporation: Research Funding; Promedior: Research Funding; Gilead: Research Funding. Miller:Incyte Corporation: Honoraria, Research Funding. Mascarenhas:Promedior: Research Funding; Roche: Research Funding; CTI Biopharma: Research Funding; Incyte Corporation: Research Funding; Novartis Pharmaceuticals Corporation: Research Funding; Kalobios: Research Funding. Thyne:Incyte Corporation: Speakers Bureau. Paranagama:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Fazal:Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Naim:Incyte Corporation: Employment, Equity Ownership. Mangan:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees.

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Evolving Real-World Treatment Patterns in Patients with Newly-Diagnosed Multiple Myeloma (NDMM) in the United States (U.S.)

Blood ◽

10.1182/blood-2019-124301 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3164-3164

Author(s):

Sikander Ailawadhi ◽

Dorothy Romanus ◽

Dasha Cherepanov ◽

Yu Yin ◽

Meng-Ru Cheng ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Research Funding ◽

Risk Group ◽

Treatment Patterns ◽

Frontline Therapy ◽

Early Cohort ◽

Recent Cohort ◽

The U.S ◽

Over Time

Background Multiple myeloma (MM), a malignant neoplasm of plasma cells in the bone marrow, accounts for up to 1.8% of all cancers in the U.S., most frequently affecting people 65-74 years old. A variety of therapies are available to manage MM, including stem cell transplantation (SCT), immunomodulatory drugs (IMiD), proteasome inhibitors (PI), monoclonal antibodies (mAB), and alkylating agents (alk). Given the heterogeneity of MM and the rapidly evolving therapeutic landscape, MM contemporaneous real-world treatment patterns are not well described. We examined the patient characteristics and first-line (LT1) treatment patterns in NDMM patients. Methods MM patients (≥18 years), diagnosed in April 30, 2015 - April 29, 2017 (early cohort) or in April 30, 2017 - April 30, 2019 (recent cohort), were followed retrospectively from MM diagnosis to last patient activity in the Flatiron Health database - a geographically-diverse, longitudinal electronic health record spanning over 280 community and academic cancer clinics in the U.S. LT1 regimens were described as: 1) containing an IMiD (thalidomide, lenalidomide [R], or pomalidomide), PI (bortezomib [V], carfilzomib, or ixazomib), alk (melphalan, cyclophosphamide [C], bendamustine), mAB (daratumumab, elotuzumab), or combinations of these; and 2) doublet/monotherapy (doublets-) vs. triplet or greater agent (triplets+) combinations. Treatment patterns were examined by SCT status and by cytogenetic risk (high: del17p, t(4;14) and/or t(14;16); standard: ≥1 cytogenetic tests without high cytogenetic risk) and age groups (<65, 65-74, ≥75). Duration of therapy (DOT) and time to next therapy (TTNT) were estimated using Kaplan-Meier methods in the early cohort with longer follow-up. Results Of 4,070 NDMM patients, 3,433 were non-SCT (nSCT: early cohort: n=1,736; recent cohort: n=1,697) and 637 had SCT (early cohort: n=407; recent cohort: n=230). In nSCT patients, mean age at diagnosis was 70 years (SD: 10); 46% were female; 36% had stage III (699/1916, among non-missing), and 15% (392/2574, among non-missing) had high risk MM (25% had unknown cytogenetics). SCT patients were younger at diagnosis (mean [SD]: 61 years [9]); 44% were female; 25% (117/470, in non-missing) had stage III, and 19% (102/547, in non-missing) had high risk MM (14% had unknown cytogenetics). Overall, proportions with known cytogenetic risk were similar within SCT status cohorts over time but were lower in the SCT group (nSCT early vs. recent cohort: 26% vs. 24% had unknown cytogenetics; and in SCT: 15% vs. 13%, respectively). In nSCT and SCT patients, respectively, most common regimens were VRd (d: dexamethasone; 44% and 58%), Rd (16% and 7%), Vd (13% and 1%), and VCd (12% and 4%). In nSCT patients, the use of VRd increased over time (37% [early cohort] to 51% [recent cohort]), while frontline therapy with Rd/Vd doublets (19% to 14%/16% to 9%) and with VCd (13% to 11%) decreased. In the nSCT recent cohort, VRd (51%) frontline therapy dominated, with a slightly higher proportion of patients in the high-risk group vs. standard and unknown risk receiving VRd (56% vs. 53% and 46%); use of doublet therapy with Rd/Vd was lower in the high risk (12%/5%) vs. standard risk group (14%/9%). Irrespective of age, VRd was the most common frontline regimen in the nSCT recent cohort, albeit its use was lower among patients 75+ years of age (43%) vs. younger patients (54% [<65 years] and 59% [65-74 years]); 75+ year old patients had a higher use of Rd/Vd doublets (19%/15%) vs. <65 (10%/5%) or 65-74 (10%/6%) years of age. Triplets+ were more commonly used than doublets- across all cohorts: 59% vs. 41% (nSCT early cohort); 74% vs. 26% (nSCT recent cohort); and 89% vs. 11% (SCT early cohort); 95% vs. 5% (SCT recent cohort). mAB use in the recent cohort was low: 1.4% nSCT and 2.2% SCT patients. In the nSCT early cohort, the median (95% CI) LT1 DOT was 10 months (9-11) and for TTNT was 14 months (13-16). Conclusions PI/IMiD treatment combinations were most commonly observed in both nSCT and SCT patients, with an increase in use from early (40%) to recent (56%) cohort in nSCT patients. Use of triplets, generally, is on the rise from early (60%) to recent cohorts (74%). LT1 TTNT was lower than has been shown in clinical trials. These findings indicate a notable change in treatment patterns over time in nSCT NDMM patients, highlighting the changing landscape of MM management. Disclosures Ailawadhi: Celgene: Consultancy; Takeda: Consultancy; Cellectar: Research Funding; Amgen: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics: Research Funding. Romanus:Takeda: Employment. Cherepanov:Takeda: Employment. Yin:Takeda: Employment. Cheng:Takeda: Employment. Hari:Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Research Funding; Janssen: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Amgen: Research Funding; Spectrum: Consultancy, Research Funding; Sanofi: Honoraria, Research Funding; Cell Vault: Equity Ownership; AbbVie: Consultancy, Honoraria.

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Phase I Dose-Escalation Study of Venetoclax Plus BEAM Followed By Autologous Stem Cell Transplant (ASCT) for Chemoresistant or High-Risk Relapsed/Refractory Non-Hodgkin Lymphoma (NHL)

Blood ◽

10.1182/blood-2021-149580 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 656-656

Author(s):

Joseph Maakaron ◽

Qiuhong Zhao ◽

Jayalakshmi Panicker Balakrishna ◽

Marcin Puto ◽

Wesley Ferguson ◽

...

Keyword(s):

High Risk ◽

Phase I ◽

Dose Escalation ◽

Research Funding ◽

Salvage Chemotherapy ◽

Publicly Traded ◽

Post Transplant ◽

The Past ◽

Car T ◽

Expansion Cohort

Abstract Introduction: Salvage chemotherapy followed by high dose therapy with carmustine, etoposide, cytarabine, and melphalan (BEAM) with ASCT is standard treatment for patients with chemosensitive, relapsed/refractory (r/r) NHL. Patients with inadequate response to salvage chemotherapy portend a worse prognosis. We present a phase I dose-escalation trial of venetoclax combined with BEAM conditioning followed by ASCT for the treatment of r/r or high-risk NHL. An expansion cohort of 10 patients was added at the highest tolerated dose. Venetoclax is an oral BCL-2 inhibitor that has significant single-agent and combination activity in r/r NHL. Preclinical observations showed that venetoclax potentiates the cytotoxicity of chemotherapy, increases synergistic cell kill, and can overcome chemoresistance even in highly aggressive lymphomas. In this trial, we aim to test the safety of the combination of venetoclax plus BEAM followed by ASCT. We hypothesize that venetoclax will help overcome the chemoresistance of these tumors and decrease post-ASCT relapse. Methods: This is an open-label, single-center, phase I trial (NCT03583424) with a dose expansion cohort of venetoclax in combination with BEAM and ASCT for patients with r/r or high-risk NHL. Venetoclax is given for 10 days, starting at D-10 before ASCT, in three dosing cohorts (400, 800, 1200 mg) using a quick ramp-up schedule. There were no dose limiting toxicities; therefore an expansion cohort of 10 additional patients accrued at the 1200 mg dose. Eligible participants include adult, fit patients with B and T-cell NHL refractory after upfront induction therapy, in partial remission or progressed after salvage, requiring ≥ 3 lines of therapy, relapsed within 1 year of induction, or at a high risk of relapse after ASCT (in first complete or partial remission). Patients with small lymphocytic lymphomas, with primary, or uncontrolled secondary, CNS lymphoma patients are excluded. Primary outcome is safety and determination of maximal tolerated dose (MTD). Adverse events (AEs) were recorded using CTCAE v 4.1 between days -10 to -6 then the Bearman scale was used from day -6 until engraftment. Results: Dose-escalation proceeded with no DLT and 19 patients were accrued across three cohorts. Baseline characteristics and safety data for all three cohorts are presented in Table 1. The majority were male (79%) and had stage IV disease (79%). The media age was 61. No unusual toxicities were encountered beyond what is expected with BEAM. No serious AEs were observed between days -10 to -6 that was related to treatment. No tumor lysis syndrome or other toxicities attributable to venetoclax were observed. Engraftment was as expected. Post-transplant, on the Bearman scale, there were no grade 3 toxicities, 5 grade 2, and 8 grade 1 toxicities. In cohort 3, 1 patient died prior to engraftment from fulminant sepsis. At 100 days post-transplant, 63% were in CR and 11% had stable disease. Fourty-seven percent remained in CR at 1 year post transplant (Table 2). After a median follow-up of 654 (range 335-957) days, median progression-free survival (PFS) was 398 days and median overall survival (OS) was not reached (Figure 1). Six patients went on to receive CD19 chimeric antigen receptor T-cell (CAR-T) therapy. Data of response according to BCL2 expression by IHC is presented in Table 3 for the 12 patients who had available data. Median PFS was superior in BCL2 positive group (p=0.04; figure 1C) Discussion: The addition of venetoclax to BEAM appears to be safe and well-tolerated in a typical, elderly population with high-risk disease and produced promising results. While CD19 CAR-T are a consideration, many patients may not have access to these therapies. Venetoclax in combination with BEAM can represent an option for patients with relapsed and refractory NHL. Figure 1 Figure 1. Disclosures Brammer: Celgene: Research Funding; Seattle Genetics: Speakers Bureau; Kymera Therapeutics: Consultancy. Maddocks: Celgene: Divested equity in a private or publicly-traded company in the past 24 months; Karyopharm: Divested equity in a private or publicly-traded company in the past 24 months; Beigene: Divested equity in a private or publicly-traded company in the past 24 months; ADC Therapeutics: Divested equity in a private or publicly-traded company in the past 24 months; Morphosys: Divested equity in a private or publicly-traded company in the past 24 months; KITE: Divested equity in a private or publicly-traded company in the past 24 months; Pharmacyclics: Divested equity in a private or publicly-traded company in the past 24 months; BMS: Divested equity in a private or publicly-traded company in the past 24 months; Merck: Divested equity in a private or publicly-traded company in the past 24 months; Novatis: Divested equity in a private or publicly-traded company in the past 24 months; Janssen: Divested equity in a private or publicly-traded company in the past 24 months; Seattle Genetics: Divested equity in a private or publicly-traded company in the past 24 months. Saad: Kadmon: Research Funding; Amgen: Research Funding; careDx: Consultancy; Incyte Pharmaceuticals: Consultancy; Magenta Therapeutics: Consultancy; OrcaBio: Research Funding. Jaglowski: Novartis: Consultancy, Research Funding; CRISPR Therapeutics: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Juno: Consultancy; Takeda: Consultancy. William: Guidepoint Global: Consultancy; Dova Pharmaceuticals: Research Funding; Merck: Research Funding; Kyowa Kirin: Consultancy; Incyte: Research Funding. OffLabel Disclosure: Venetoclax is a BCL2 inhibitor approved for treatment of hematological malignancies (AML and CLL).

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Treatment Patterns and Outcomes Among Patients with Relapsed/Refractory Follicular Lymphoma Treated in Routine Clinical Practice in the US with Three or More Lines of Therapy

Blood ◽

10.1182/blood-2021-145412 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4080-4080

Author(s):

Jamie T. Ta ◽

Stella Arndorfer ◽

Cristina Julian ◽

Mei Wu ◽

Dominic Lai ◽

...

Keyword(s):

Follicular Lymphoma ◽

Real World ◽

Treatment Initiation ◽

Treatment Patterns ◽

Publicly Traded ◽

The Past ◽

Community Oncology ◽

The Us ◽

Early Progression

Abstract Background: Follicular lymphoma (FL) is an indolent, yet incurable disease, and patients often require several lines of therapy throughout their lifetime (Batlevi et al. Blood Cancer J 2020); however, there are limited real-world data available regarding the treatment of a contemporary cohort of patients with relapsed/refractory (R/R) FL. The objective of this study was to assess real-world treatment patterns and outcomes among patients receiving third- and later-line (3L+) therapies for FL in the US. Methods: This retrospective cohort study used the nationwide Flatiron Health electronic health record-derived de-identified database. During the study period, de-identified data originated from approximately 280 cancer clinics (~800 sites of care) in the US. We selected patients aged ≥18 years with an initial FL diagnosis between January 2011 and January 2021, who had received at least 3 lines of therapy for FL (follow-up ended March 2021). Exclusion criteria included: evidence of clinical trial participation during the study period, high-grade (3b) FL at diagnosis, transformation to an aggressive lymphoma any time before 3L FL treatment, or other anticancer therapies or stem cell transplant 12 months before first-line (1L) FL treatment. Patient demographic and clinical characteristics were assessed using descriptive statistics. Treatment patterns and time to next anti-lymphoma treatment or death (TTNTD) were reported. Median TTNTD was estimated using Kaplan-Meier methods. Results: Of 2,990 patients receiving treatment for FL during the study period, 157 patients who received at least 3 lines of therapy for FL were included. Median age at time of 3L FL treatment initiation was 70 years, and 48.4% (n=76) of patients were male. At initial FL diagnosis, 79.6% (n=125) had low-grade (1-2) FL, 78.3% (n=123) had advanced stage (III/IV) FL, and 68.6% (n=48) of the 70 patients with available Follicular Lymphoma International Prognostic Index (FLIPI) scores had high-risk FLIPI (≥3). Overall, 68.2% of patients had evidence suggestive of early progression of disease within 24 months of 1L FL treatment. The majority of patients were treated at community oncology practices (n=140 [89.2%]). Median time to 3L treatment initiation from diagnosis was 35.6 months, and median follow-up after 3L treatment was 15.4 months. Fifty-two (33.1%) patients received a subsequent fourth-line therapy. The most common 3L treatment regimens received were rituximab (R) monotherapy (n=32 [20.4%]), R plus bendamustine (n=26 [16.6%]), R plus lenalidomide (n=18 [11.5%]), obinutuzumab monotherapy (n=14 [8.9%]), and idelalisib (n=13 [8.3%]; Table). Median TTNTD after 3L treatment was 14.1 months (95% confidence interval: 10-23.6; Figure). Conclusions: Our study provides an update on the heterogeneous treatment landscape for R/R FL in the US for patients receiving 3L+ therapy in real-world clinical practice, the majority of whom were treated in community oncology practices. Many patients requiring 3L+ FL treatment had clinical characteristics predictive of poor prognosis, as evidenced by the high proportion of patients who had evidence of early progression and high-risk FLIPI at diagnosis. Treatment outcomes following 3L therapy remain poor, and approximately one-third of patients required additional treatment beyond 3L. Limitations of this analysis include those inherent to real-world observational databases and the relatively short follow-up of patients with indolent FL in the Flatiron Health database, particularly following 3L FL treatment. Future studies with additional follow-up are warranted. Nevertheless, these findings highlight the ongoing unmet need for novel, effective treatments in this setting in order to improve patient outcomes. Figure 1 Figure 1. Disclosures Ta: Genentech, Inc.: Current Employment. Arndorfer: Genesis Research: Consultancy, Current Employment. Julian: Genentech, Inc.: Current Employment, Current holder of stock options in a privately-held company. Wu: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Lai: Bristol-Myers Squibb: Current equity holder in publicly-traded company; AbbVie: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months; Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Shapouri: F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment.

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Trends in Prescribing Practices for Management of Hemophilia

Blood ◽

10.1182/blood-2021-153828 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2112-2112

Author(s):

Randall Curtis ◽

Jonathan C. Roberts ◽

Nicole Crook ◽

Marquita Decker-Palmer ◽

Rahul Khairnar ◽

...

Keyword(s):

Gene Therapy ◽

Research Funding ◽

Clotting Factor ◽

Prescribing Practices ◽

Publicly Traded ◽

Major Life ◽

The Past ◽

The Us ◽

Life Threatening ◽

High Doses

Abstract Introduction: Over the past 21 years, treatment options for hemophilia have evolved significantly. The objective of this study is to describe the trends observed in clinician prescribing practices for management of hemophilia A (HA) and B (HB) in the United States (US) via three surveys from 1999-2021. Methods: We administered surveys to members of the Hemostasis & Thrombosis Research Society (HTRS) via an in-person paper survey at its annual symposia in 1999 and 2015, and an online survey in 2021. The survey participants included physicians, physician assistants, and nurse practitioners who manage the care of hemophilia patients at hemophilia treatment centers in the US. The surveys collected information regarding: 1) characteristics of clinician practice, 2) prescribed clotting factor products and dosages used for routine bleeds or major life-threatening bleeding, total joint replacement, and port placement, 3) reasons for changing doses, 4) frequency of recommendation for prophylaxis and inhibitor treatment for associated factor and non-factor products, and 5) gene therapy. Results: Forty-one clinicians completed the survey in 1999 and 2021, 53 in 2015. The mean number of patients seen by respondents increased from 142 (range: 0-314) for children and 101 (0-480) for adults in 1999 to 202 (0-900) for children and 154 (0-500) for adults in 2021. The proportion of clinicians prescribing >40 units/kg of Standard Half Life (SHL) Factor IX concentrates for routine bleeding events in HB patients increased from 22.5% in 1999 to 50.9% in 2015, and 87.8% in 2021. The proportion of clinicians reported SHL Factor VIII usage for routine bleeding at a dose of >40 units/kg in HA patients increased from none in 1999 to 11.3% in 2015 and 29.3 % in 2021. The reported rates of prescribing an average >60 units/kg factor to treat major life-threatening bleeds increased from 67.5% in 1999 to 90.3% in 2021 for HB; rates were 2.5% in 1999, 17.3% in 2015 and 7.3% in 2021 for treating HA. For children <4 years old, 22.2% of clinicians prescribed primary prophylaxis all of the time in 1999. This rose to 68.2% in 2015, and 86.5% in 2021. For adults, 12.5% of clinicians prescribed secondary prophylaxis all of the time in 1999, 27.3% in 2015 and 42.5% in 2021. For treatment of patients with HA or HB inhibitors, the proportions of clinicians who reported prescribing immune tolerance induction (ITI) therapy all of the time for pediatric patients were 50%, 75.0% and 63.2% in three surveys, but <25% for adult patients. In the 2021 survey, >91% of clinicians reported prescribing emicizumab to treat HA inhibitors in patients of all ages, while >87% reported prescribing it to treat HA without inhibitor. Clinicians were more likely to always prescribe emicizumab to treat HA patients with inhibitors (63.2% for children and 57.1% for adults), as compared to always prescribing it for those without inhibitors (13.2% for children and 5.7% for adults). The most frequent reported method to treat a patient with a history of inhibitors on emicizumab who had break through bleeds was rFVIIa: 85.4% for children, and 75.6% for adults. The most frequently reported reasons for switching from FVIII to emicizumab were fewer injections/visits (87.8%), and improved patient quality of life (82.9%). Thirty-nine percent of clinicians reported caring for patients currently in gene therapy trials, 27.5% had patients who had completed gene therapy. When asked about potential future prescribing practices, 14.6% reported that they would prescribe gene therapy "all the time", 4.9% would prescribe it "about 3/4 of the time", 29.3% "about 1/2 the time", 29.3% "about 1/4 the time", and 22.0% "rarely or never". Conclusion: These data indicate changes in prescribing practices among hemophilia specialists in the US over the past 21 years. Prescribing of high doses of factor (>40 units/kg) increased, while ITI prescribing practices remained similar over time. To treat patients with major life-threatening bleeds, a larger proportion of clinicians prescribed high doses of factor (>60 units/kg) for patients with HB as compared to HA. Most clinicians frequently prescribed emicizumab for patients with HA inhibitors, but less frequently for those without inhibitors. At this time, there is wide diversity among clinicians in the expected uptake of gene therapy. Disclosures Curtis: Pfizer, Bayer, and Novo Nordisk: Consultancy; University of Southern California: Consultancy. Roberts: Takeda; Speakers Bureau: Novo Nordisk, Octapharma, Sanofi, Takeda.: Research Funding; Genentech, Novo Nordisk, Octapharma, Pfizer, Sanofi, Takeda, uniQure: Consultancy. Decker-Palmer: Genentech Inc. --A member of the Roche Group.: Current Employment, Current equity holder in publicly-traded company. Khairnar: Genentech Inc - A Member of The Roche Group: Current Employment; University of Maryland, Baltimore: Ended employment in the past 24 months; Roche: Current equity holder in publicly-traded company. Wu: Baxalta US Inc., Bannockburn, IL (a Takeda Company), CSL Behring L.L.C., Octapharma USA, Inc., Genentech Inc.: Research Funding. Nichol: Pfizer, Genentech Inc., Baxalta US Inc., Bannockburn, IL (a Takeda Company), Octapharma, CSL Behring, Global Blood Therapeutics, and Novo Nordisk: Research Funding.

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Mechanisms of Adaptation to Ibrutinib in High Risk Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood-2018-99-116739 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 585-585 ◽

Cited By ~ 4

Author(s):

Valeria Spina ◽

Gabriela Forestieri ◽

Antonella Zucchetto ◽

Alessio Bruscaggin ◽

Tamara Bittolo ◽

...

Keyword(s):

High Risk ◽

Chronic Lymphocytic Leukemia ◽

Nuclear Localization ◽

Peripheral Blood ◽

Research Funding ◽

Clonal Evolution ◽

Lymphocytic Leukemia ◽

Adaptation Process ◽

Over Time ◽

Stimulation Of

Abstract Introduction. Ibrutinib inhibits the BTK molecule downstream the B-cell receptor (BCR). Though highly active in high risk chronic lymphocytic leukemia (CLL), the most typical response achievable in patients is a minimal residual disease (MRD) positive partial remission (PR) which is maintained until the development of genetically driven resistance caused by the acquisition of mutations in the BTK or PLCG2 genes. The study aims at characterizing the adaptation process allowing residual CLL cells to persist despite BTK inhibition. Methods. The IOSI-EMA-001 study (NCT02827617) is an observational study consisting in the prospective and longitudinal collection of peripheral blood samples and clinical data from high risk CLL patients treated with ibrutinib. Peripheral blood CLL cells longitudinally drawn from patients before treatment start and at fixed timepoints under ibrutinib were monitored by: i) next generation flow cytometry approaches for changes in proliferation rate, surfaceome, and pathway activation; and ii) CAPP-seq targeted deep next generation (sensitivity ~10-3) for clonal evolution. Results. The study cohort comprised 31 high risk CLL patients, including 15 treatment naïve, 16 relapsed, 80% IGHV unmutated, 42% 17p deleted and 55% TP53 mutated. Median duration of ibrutinib treatment was 45 weeks (24-72 weeks). All patients obtained a MRD positive PR that was maintained in all but one who progressed with a PLCG2 mutation (VAF 3%). Compared to baseline, under ibrutinib therapy CLL cells slowed down their proliferation, as suggested by the decreased expression of Ki-67, the reduction of the proliferating fraction (CXCR4dimCD5bright), and the increase of the resting fraction (CXCR4brightCD5dim). Compared to baseline, under ibrutinib therapy CLL cells also upregulated BCR and adhesion/homing proteins, and decreased the expression of BCR inhibitor proteins. Upon stimulation of the BCR with anti-IgM, the downstream path through pBTK and pPLCG2 was inhibited by ibrutinib, while conversely the downstream path through pAKT and pERK was still inducible throughout all the assessed timepoints. The proportion of CLL cells harboring nuclear localization of NF-kB progressively increased over time under ibrutinib. NF-kB nuclear localization was inducible throughout all the assessed timepoints by CD40L stimulation of the non-canonical NF-kB pathway, but not by anti-IgM stimulation of the BCR/canonical NF-kB pathway. Overall, 880 individual mutations were longitudinally discovered and monitored across a total of 121 sequential timepoints collected during ibrutinib treatment. Clonal evolution was observed in (67.7%) cases, a proportion rate previously documented in CLL treated with chemoimmunotherapy. Clonal evolution appeared to be heterogeneous involving different genes without a stereotypic targeting. Consistently, none of the main driver gene mutations was homogeneously selected or suppressed by ibrutinib suggesting that the biological adaptation of CLL cells under ibrutinib is not genetically driven. Clonal evolution propensity was not associated with any of the biomarkers of the disease, and it did not decrease over time under ibrutinib. Conclusions. Taken together these results suggest that residual CLL cells persisting under ibrutinib therapy adapt their phenotype by upregulating adhesion molecules, chemokine receptors and BCR molecules, and by maintaining a competence of BCR signaling through the PI3K/AKT/ERK pathway. The progressive selection of CLL cells having NF-kB in the nucleus, likely due to the BTK independent non-canonical NF-kB pathway, might explain their survival despite ibrutinib therapy. Finally, clonal evolution is not suppressed by ibrutinib chemotherapy, and despite does not seem to be directly involved in such adaptation process, may ultimately favor the acquisition of BTK and PLCG2 ibrutinib resistance mutations. Disclosures Zucca: Celltrion: Consultancy; AstraZeneca: Consultancy. Ghia:Sunesis: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; AbbVie, Inc: Honoraria, Research Funding; Acerta: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; BeiGene: Honoraria, Research Funding. Montillo:Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Research Funding. Tedeschi:Janssen: Consultancy, Speakers Bureau; Gilead: Consultancy; AbbVie: Consultancy. Gaidano:AbbVie: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Morphosys: Honoraria; Roche: Consultancy, Honoraria.

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Discordance between Treatment Guideline Recommendations and Real-World Practice in a Group of Large Integrated Delivery Networks for Venous Thromboembolism (VTE) Patients: A Closer Look at VTE Patients with Cancer

Blood ◽

10.1182/blood-2021-150493 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1951-1951

Author(s):

Juzer Lotya ◽

Amol Dhamane ◽

Lisa Rosenblatt ◽

Jenny Jiang ◽

Deysia Levin ◽

...

Keyword(s):

African American ◽

Research Funding ◽

Treatment Patterns ◽

Morbidly Obese ◽

Anticoagulant Treatment ◽

Publicly Traded ◽

Patients With Cancer ◽

Integrated Delivery ◽

Delivery Networks ◽

Current Guidelines

Abstract Background: For patients with VTE, current American Society of Hematology (ASH) guideline panel suggests using direct oral anticoagulants (DOACs) over vitamin K antagonists (VKAs) where VKAs are required to be bridged with a parenteral anticoagulant (PAC). For patients with VTE and cancer, current guidelines recommend DOACs over low molecular weight heparin (LMWH) and LMWH over unfractionated heparin (heparin) for the initial treatment of VTE. Limited evidence is available about the patterns of anticoagulant treatment for VTE in routine clinical practice of large healthcare delivery networks in the United States (US) and whether the VTE treatments are aligned with current guidelines. This study aimed to assess real-world anticoagulant treatment patterns among VTE patients using harmonized electronic health record (EHR) data from four Integrated Delivery Networks (IDNs) in the US. Methods: This was a retrospective, longitudinal, multicenter, cohort study using harmonized EHR data from both inpatient and outpatient settings. The study population included adult patients prescribed DOACs, warfarin, and/or PAC therapy as inpatient or outpatient treatment within ≤30 days of VTE diagnosis, between June 2015 through May 2018. Data from the four IDNs was pooled to describe demographic characteristics and treatment patterns among VTE patients overall and by subgroups. Results: A total of 10,527 patients who were treated with OACs after VTE diagnosis were included for analysis. The mean (SD) age was 61.9 (5.98) years, with 46.1% aged 65 or older. More than half (53.2%) were female, and White patients comprised the majority (74.4%), followed by African American patients (22.8%). Obese and morbidly obese patients comprised 39.1% and 16.1% of patients, respectively. Among all VTE patients, warfarin-only (n=3545; 33.7%) was the most commonly used OAC treatment, followed by warfarin + PAC (n=3128; 29.7%), rivaroxaban-only (n=1357; 12.9%), rivaroxaban + PAC (n=853; 8.1%), apixaban + PAC (n=839; 8.0%), apixaban-only (n=762; 7.2%), and Other OAC (n=357; 3.4%) (Table 1). When stratifying VTE patients by age, gender, race and BMI, some variations in OAC treatment were observed. Among both older (≥65 years) and younger (<65 years) patients, warfarin-only was most commonly used, then warfarin + PAC. Warfarin-only was more commonly used among obese (36.3%) and morbidly obese (40.4%) patients than non-obese (29.8%) patients. OAC treatment patterns were generally comparable among men and women. Among White patients, approximately equal proportions of patients received warfarin + PAC (31.9%) and warfarin-only (31.0%). However, among African-American patients, a higher proportion of patients used warfarin-only (40.9%) vs. warfarin + PAC (24.5%). Patterns of anticoagulant treatments including OACs and/or parental anticoagulants among VTE patients with cancer were further analyzed (Figure 1). Among VTE patients with cancer (n=3657), heparin had the highest use (26.7%), then enoxaparin (22.7%); approximately the same proportion of cancer patients received warfarin-only (16.0%) and warfarin + PAC (16.9%). Of DOACs, rivaroxaban-only was the most commonly used treatment (4.9%), then apixaban + PAC (3.5%), and lastly, rivaroxaban + PAC (3.4%) among cancer patients. Conclusion: Current VTE treatment guidelines recommend warfarin to be bridged with PAC, however, warfarin-only therapy remained the most used treatment option followed by warfarin + PAC. While rivaroxaban and apixaban are not required to be bridged with PAC, such practices were observed for a large proportion of apixaban- and rivaroxaban-treated VTE patients. VTE treatment among patients with cancer was not completely aligned with current guidelines, as heparin was more commonly used than LMWH (enoxaparin). Our findings suggest greater efforts are needed to improve anticoagulant treatment practices among VTE patients. Figure 1 Figure 1. Disclosures Dhamane: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Rosenblatt: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Jiang: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Guo: Bristol Myers Squibb: Ended employment in the past 24 months. Dorsch: Agency for Health Research and Quality: Research Funding; National Institutes of Health/National Institute of Aging: Research Funding; American Health Association Health IT Research Network: Research Funding; Janssen Pharmaceuticals: Honoraria; Bristol Myers Squibb/Pfizer: Research Funding; Amgen: Research Funding. Luo: Pfizer Inc: Current Employment, Current equity holder in publicly-traded company.

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To Treat or Not to Treat? Understanding Treatment Patterns in Patients with Lower-Risk Myelofibrosis at the Time of Enrollment in the MOST Study

Blood ◽

10.1182/blood-2020-134958 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 49-51

Author(s):

Rami S. Komrokji ◽

Brady L. Stein ◽

Robyn M. Scherber ◽

Patricia Kalafut ◽

Haobo Ren ◽

...

Keyword(s):

Board Of Directors ◽

Lower Risk ◽

Research Funding ◽

Symptom Burden ◽

Risk Groups ◽

Treatment Patterns ◽

Low Risk ◽

Publicly Traded ◽

Advisory Committees ◽

Therapy Initiation

Background: Myelofibrosis (MF) is a chronic Philadelphia chromosome-negative myeloproliferative neoplasm (MPN) characterized by extramedullary hematopoiesis, bone marrow fibrosis, splenomegaly, constitutional symptoms, and diminished quality of life. Treatment decisions may involve a variety of factors including prognosis and symptomatology. Data regarding real-world disease and demographic factors that contribute to therapy initiation and choice in pts with lower risk MF are limited. This analysis of data from the ongoing Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST; NCT02953704) assessed whether these factors differ for lower risk pts who were treated vs untreated at enrollment. Methods: MOST is a longitudinal, noninterventional, prospective, observational study in pts with MF or essential thrombocythemia enrolled at clinical practices within the US. Pts included in the analysis (≥18 y), had low risk MF by the Dynamic International Prognostic Scoring System (DIPSS; Blood. 2010;115:1703), or intermediate-1 (INT-1) risk by age >65 y alone. Pt data were entered into an electronic case report form during usual-care visits over a planned 36-month observation period. Pt-reported symptom burden was assessed using the MPN-Symptom Assessment Form (MPN-SAF); Total Symptom Score (TSS) was calculated (0 [absent] to 100 [worst imaginable]; J Clin Oncol. 2012;30:4098). Data were analyzed with basic descriptive and inferential statistics. Results: Of 233 pts with MF enrolled at 124 sites between 11/29/2016 and 03/29/2019, 205 were included in this analysis; 28 were excluded for being INT-1 risk for reasons other than age. Of the 205 pts, 85 (41.5%) were low- and 120 (58.5%) were INT-1 risk; 56.5% (48/85) and 59.2% (71/120), respectively, were being treated at enrollment. Pt characteristics are listed in Table 1A. Fewer low- vs INT-1 risk pts were JAK2 V617F or MPL positive, and more were CALR positive. The proportion of pts with palpable splenomegaly was similar for treated low- and INT-1 risk pts. In low risk pts, the proportion of pts with palpable splenomegaly was higher in untreated vs treated pts; whereas, in INT-1 risk pts, the opposite was observed (ie, lower proportion in untreated vs treated pts). Blood counts were generally similar across cohorts, except median leukocytes were lower for low risk treated pts and platelet counts were elevated in low- vs INT-1 risk pts. The proportion of pts with comorbidities was similar across cohorts, except for fewer cardiovascular comorbidities in low- vs INT-1 risk pts. Mean TSS was lower in low- vs INT-1 risk pts, but the proportion of pts with TSS ≥20 was greater in treated vs untreated pts in both low- and INT-1 risk groups. Fatigue was the most severe pt-reported symptom in all cohorts. Differences in mean TSS and individual symptom scores between risk groups were not significant (P > 0.05), except itching was worse among INT-1 risk pts (P=0.03). Physician-reported signs and symptoms were generally more frequent for untreated vs treated pts, irrespective of risk (all P > 0.05). Most low risk (69.4%) and INT-1 risk pts (61.2%) who were currently untreated at enrollment had not received any prior MF-directed treatment (Table 1B); the most common prior treatment among currently untreated pts was hydroxyurea (HU) in both risk groups. Of currently treated pts, HU was the most common MF-directed monotherapy at enrollment in low-risk pts, and ruxolitinib was most common in INT-1 risk pts. No low risk pts and few INT-1 risk pts were currently receiving >1 MF-directed therapy at enrollment. Conclusion: These real-world data from pts with MF enrolled in MOST show that a substantial proportion of both low- and INT-1 risk pts who had received treatment before enrollment were not being treated at the time of enrollment. Although watch-and-wait is a therapeutic option, the finding that many of these lower risk pts had in fact received prior therapies suggests an unmet need for effective and tolerable second-line treatment options. Treated pts had greater pt-reported symptom burden vs untreated pts, which suggests that high symptom burden may contribute to the decision for treatment. Prospective studies are needed to evaluate symptom burden change with therapy initiation. In this regard, future analyses of data from MOST are planned to assess the longitudinal evolution of the clinical characteristics, treatment patterns, and management of pts with MF. Disclosures Komrokji: Geron: Honoraria; Agios: Honoraria, Speakers Bureau; AbbVie: Honoraria; Incyte: Honoraria; Novartis: Honoraria; BMS: Honoraria, Speakers Bureau; JAZZ: Honoraria, Speakers Bureau; Acceleron: Honoraria. Stein:Incyte: Research Funding; Kartos: Other: educational content presented; Constellation Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pharmaessentia: Membership on an entity's Board of Directors or advisory committees. Scherber:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Kalafut:Incyte: Current Employment, Current equity holder in publicly-traded company. Ren:Incyte: Current Employment, Current equity holder in publicly-traded company. Verstovsek:Incyte Corporation: Consultancy, Research Funding; Roche: Research Funding; Genentech: Research Funding; Blueprint Medicines Corp: Research Funding; CTI Biopharma Corp: Research Funding; NS Pharma: Research Funding; ItalPharma: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; Protagonist Therapeutics: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; PharmaEssentia: Research Funding; AstraZeneca: Research Funding; Promedior: Research Funding.

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Healthcare Resource Utilization and Sickness Absence in Newly Diagnosed Multiple Myeloma Patients in Sweden: Trends in a Changing Treatment Landscape

Blood ◽

10.1182/blood-2020-137498 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 17-18

Author(s):

Fredrik Borgsten ◽

Xenia Gatopoulou ◽

Marta Pisini ◽

Magnus Tambour ◽

Frida Schain ◽

...

Keyword(s):

Multiple Myeloma ◽

Sickness Absence ◽

Healthcare Resource ◽

Productivity Loss ◽

Healthcare Resource Utilization ◽

Publicly Traded ◽

The Third ◽

The Past ◽

Over Time

Background In the last decades the introduction of novel drugs has greatly improved the prognosis of multiple myeloma (MM) patients. We have investigated healthcare resource utilization and sickness absence-associated productivity loss over time in a population-wide, retrospective registry study in Sweden. Methods 8,693 patients were identified in the National Cancer Register with a MM diagnosis from July 2001 to December 2015 and followed until 2016. Specialized healthcare usage (inpatient admissions and outpatient visits) were obtained from the Patient Register and costs were estimated by weighted DRG codes. For patients under 66 years of age, sickness absence and salary information were obtained by linkage to the LISA Register. Analyses were performed separately on patients who underwent autologous stem cell transplantation (ASCT) (n=1,425) and on non-transplanted patients (n=7,012) and stratified by diagnosis periods 2001-2005, 2006-2010 and 2011-2015 to reflect increased introduction of effective drugs into clinical care. Median age was 60 years in the ASCT group and 75 years in the non-ASCT group. Results The number of MM patients that underwent ASCT increased over time (n= 282 in 2001-2006 to n= 592 in 2011-2015). MM patients diagnosed most recently had improved overall survival (OS), with five-year OS rate increasing from 52% to 58% to 62% for patients diagnosed in 2001-2005, 2006-2010 and 2011-2015, respectively (p<0.0001). Patients diagnosed during 2011-2015 spent on average 20% and 9% less total time in specialized healthcare than patients diagnosed during 2001-2005 and 2006-2010, respectively (adjusting for sex, age at ASCT, weighted comorbidity score at ASCT and per follow-up year and education at ASCT). This decrease was driven by less usage and time in both inpatient and outpatient care. Adjusted sickness absence time decreased by 41% and 38% in the third follow-up year for patients diagnosed during 2011-2015 compared to patients diagnosed during 2001-2005 and 2006-2010, respectively. Productivity loss costs represented about 45% of total costs (healthcare resource costs ~55%) in the first two follow-up years, but decreased over time. The cumulative median per person cost (healthcare- and productivity-related) over the three follow-up years post-diagnosis decreased by 21% in 2011-2015 (€52,273) compared to 2001-2005 (€66,182), despite an 8% increase in three-year OS over the same period. The number of non-ASCT MM patients also increased over time (n=2,053 in 2001-2005 to n= 2,587 in 2011-2015). Median survival increased from 2.5 years to 3.4 years for patients diagnosed during 2001-2005 compared to 2011-2015. Average total time spent in specialized healthcare was reduced by 29% and 12% for patients diagnosed during 2011-2015, compared to patients diagnosed during 2001-2005 and 2006-2010, respectively (adjusting for sex, age at diagnosis, weighted CCS at diagnosis, weighted CCS per follow-up year and education at diagnosis). This was associated with decreased need for inpatient care and a shift towards more outpatient usage. By the third follow-up year, the adjusted sickness absence time in patients diagnosed during 2011-2015 was reduced by 44% and 23% compared to patients diagnosed in 2001-2005 and 2006-2010, respectively. Productivity loss accounted for approximately 15% of total costs (healthcare resource costs ~85%) and was stable over follow-up years. The cumulative median per-person cost (healthcare- and productivity-related) over three follow-up years was similar for patients diagnosed in 2001-2005 (€25,621) and 2011-2015 (€26,592), despite a 12% increase in three-year OS over the same period. Conclusion The availability of new treatment options for MM patients in Sweden over time was associated with less healthcare usage, less time spent in healthcare and lower productivity loss due to sickness absence for both ASCT and non-ASCT-treated patients. These improved clinical and economic outcomes provide policy makers, healthcare providers and physicians with invaluable real-world insights for cost-benefit considerations in the continued development and introduction of effective treatments for MM. Figure 1 Disclosures Borgsten: Janssen: Current Employment. Gatopoulou:Janssen: Current Employment. Pisini:Janssen: Current Employment. Tambour:Janssen: Current Employment, Current equity holder in publicly-traded company. Schain:Schain Research: Current Employment, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months. Jones:Schain Research: Current Employment. Kwok:Schain Research: Other: Internship . Hjortsberg:Janssen: Current Employment.

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