Design and implementation of a mobile app for the pharmacotherapeutic follow-up of patients diagnosed with immune-mediated inflammatory diseases: eMidCare (Preprint)

BACKGROUND Pharmacotherapeutic management of immune-mediated inflammatory diseases (IMID) has become more complex due to the development of new treatments, such as biological therapies. Mobile health, especially apps, can provide IMID patients with greater autonomy and facilitate communication with healthcare professionals. OBJECTIVE Our objective was to design and implement an app for remote monitoring and communication with IMID patients. We also assessed the usability of and satisfaction with the app. METHODS A multidisciplinary group comprising pharmacists, dermatologists, rheumatologists, gastroenterologists, and nurses was created to design and develop an app for IMID patients in a tertiary hospital. The app functionalities were identified through a focus group with IMID patients and through an observational, cross-sectional, descriptive study of all available apps for IMID patients at App Store and Play Store platforms. Once the app was designed and developed, we started offering the app to all IMID patients who initiated a new biological therapy. We performed an observational, longitudinal study of patients followed using the app to assess the tool's impact on safety, communication, satisfaction, and usability. The inclusion period was from December 2020 to August 2021. The inclusion criteria were age ≥ 18 years, diagnosis of an IMID, and ownership of a Smartphone. Patients with language barriers were excluded. RESULTS We designed an app (eMidCare®) with the following modules: My Medication, My Questionnaires, Adverse Events, Useful Information, Messages, and Patient Profile. A total of 86 patients were installed with the app (the median age was 48.3 [18.1-79.4] years and 62.4 were female). The median (range) follow-up time for app use was 123 (5-270) days. In the My Medication module, 100% of patients registered their biological therapy and 25.9% also used this module to record each dose of medication administered. A total of 82 adverse events (AEs) were registered. Thirty-two percent of the patients registered at least 1 AE. The most frequent AEs were fatigue, injection site reaction, headache, and nausea. Fifty-two percent of patients used the Messages module to communicate with healthcare professionals. The most frequent messages concerned doubts about managing AEs (26.2%) and drug interactions (18.9%). The satisfaction survey yielded a median (range) score of 9.1 (7-10) out of 10. The app sections that patients browsed for the longest time were Messages (21.9%), Start screen (20.9%), My questionnaires (20.4%), My medication (8.8%), and Adverse events (7.1%). CONCLUSIONS We developed an app, eMidCare®, which reminds patients to take their medication, enables them to record AEs, and helps them communicate with healthcare professionals. Approximately one-third of the patients registered the administration of the biological therapies and registered at least 1 AE. The most used and most satisfactory functionality was communication with health professionals. Patient satisfaction and retention were very high.

A phase II study of talimogene laherparepvec for patients with inoperable locoregional recurrence of breast cancer

Talimogene laherparepvec (T-VEC) is an immunotherapy that generates local tumor lysis and systemic antitumor immune response. We studied the efficacy of intratumoral administration of T-VEC as monotherapy for inoperable locoregional recurrence of breast cancer. T-VEC was injected intratumorally at 106 PFU/mL on day 1 (cycle 1), 108 PFU/mL on day 22 (cycle 2), and 108 PFU/mL every 2 weeks thereafter (cycles ≥ 3). Nine patients were enrolled, 6 with only locoregional disease and 3 with both locoregional and distant disease. No patient completed the planned 10 cycles or achieved complete or partial response. The median number of cycles administered was 4 (range, 3–8). Seven patients withdrew prematurely because of uncontrolled disease progression, 1 withdrew after cycle 3 because of fatigue, and 1 withdrew after cycle 4 for reasons unrelated to study treatment. Median progression-free survival and overall survival were 77 days (95% CI, 63–NA) and 361 days (95% CI, 240–NA). Two patients received 8 cycles with clinically stable disease as the best response. The most common grade 2 or higher adverse event was injection site reaction (n = 7, 78%). Future studies could examine whether combining intratumoral T-VEC with concurrent systemic therapy produces better outcomes.

Depot Pure GnRH Antagonist for Long-term Treatment of Ovarian Hyperthecosis Monitored by Multi-Steroid LCMS Profiling

Ovarian hyperthecosis (OHT), severe hyperandrogenism after menopause in the absence of ovarian or adrenal tumors, is usually treated by surgical excision. We report a 58-year-old woman presenting with severe hyperandrogenism (serum testosterone 15.7-31.0 nmol/L, normal female <1.8 nmol/L) with menopausal gonadotropins and virilization but no adrenal or ovarian lesions. Multi-steroid profiling by liquid chromatography-mass spectrometry (LCMS) of adrenal and ovarian vein samples identified strong gradients in left ovarian vein (10-30-fold vs peripheral blood in 17OHP4, 17 OHP5, A4, T, DHEA) but right ovarian vein could not be cannulated with the same findings in a second ovarian vein cannulation. OHT diagnosis was confirmed by an injection of a depot pure GnRH antagonist (80 mg Degarelix, Ferring) producing a rapid (< 24hr) and complete suppression of ovarian steroidogenesis as well as serum LH and FSH lasting at least 8 weeks with reduction in virilization but injection site reaction and flushing and vaginal spotting, ameliorated by an estradiol patch. Serum testosterone remained suppressed at 313 days after the first dose despite recovery of menopausal gonadotropins by day 278 days. This illustrates use of multi-steroid LCMS profiling for confirmation of the OHT diagnosis by ovarian and adrenal vein sampling and monitoring of treatment by peripheral blood sampling. Injection of a depot pure GnRH antagonist produced rapid and long-term complete suppression of ovarian steroidogenesis maintained over 10 months. Hence a depot pure GnRH antagonist can not only rapidly confirm the OHT diagnosis but also induce long-term remission of severe hyperandrogenism without surgery.

Subcutaneous Epcoritamab in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Preliminary Results from the Epcore CLL-1 Trial

Background: Small molecules such as Bruton tyrosine kinase (BTK) and B-cell lymphoma 2 (BCL2) inhibitors have transformed the management of chronic lymphocytic leukemia (CLL). However, such treatments are not curative, and patients (pts) with relapsed or refractory (R/R) CLL following multiple targeted treatments present an emergent challenge with very limited therapeutic options. In addition, success rates of autologous T-cell-based therapies in CLL have been disappointing. In vitro data in CLL cells suggest potentially high efficacy of bispecific T-cell engagers (Martens et al, J Immunother Cancer 2020), but clinical data are extremely limited. Epcoritamab (GEN3013; DuoBody ®-CD3×CD20) is a bispecific antibody that can induce potent activation and cytotoxic activity of CD4+ and CD8+ T cells to specifically eliminate CD20-expressing cells (van der Horst et al, Blood Cancer J 2021). In the first-in-human trial in R/R B-cell non-Hodgkin lymphoma (B-NHL; EPCORE NHL-1; NCT03625037), epcoritamab showed manageable safety and meaningful antitumor activity across a range of aggressive and indolent B-NHLs. The most common treatment-emergent adverse events (AEs) were pyrexia (69%), cytokine release syndrome (CRS; 59%), and injection-site reaction (47%); CRS events were all grade 1-2 and most occurred in cycle 1 (Clausen et al, J Clin Oncol 2021). However, as CLL is characterized by presence of (high numbers of) circulating tumor cells, acquired T-cell dysfunction, and variable expression of CD20, data obtained in B-NHL are difficult to extrapolate to CLL. Herein we present the first results from the dose-escalation part of a phase 1b/2 trial evaluating epcoritamab in pts with R/R CLL. Methods: In this open-label, multicenter, phase 1b/2 trial, toxicity and efficacy of epcoritamab are investigated in adults with R/R CLL (EPCORE CLL-1; NCT04623541). Eligible pts previously received ≥2 lines of systemic antineoplastic therapy, including treatment with (or intolerance to) a BTK inhibitor. Epcoritamab is subcutaneously administered via 1-mL injections in 4-week cycles as follows: once weekly in cycles 1-3, every 2 weeks in cycles 4-9, and monthly in cycles ≥10 until progression or unacceptable toxicity. Step-up dosing during cycle 1 (ie, priming dose followed by an intermediate dose, then full doses) is used in combination with steroid prophylaxis to reduce the risk of CRS. In the dose-escalation part, pts with R/R CLL received epcoritamab at 2 full-dose levels (24 and 48 mg) according to a modified 3+3 design. Primary end points of the dose-escalation part included dose-limiting toxicities (DLTs) during the first 28-day treatment cycle and the incidence and severity of AEs, CRS, immune effector cell-associated neurotoxicity syndrome (ICANS), and tumor lysis syndrome (TLS). Results: The first pt was enrolled on November 30, 2020. As of July 12, 2021, 7 pts with R/R CLL received epcoritamab subcutaneously administered at 2 full-dose levels: 24 mg (n=3) and 48 mg (n=4). Six pts completed the DLT evaluation period, and 5 pts had a full response assessment. Pts had received a median of 4 lines of prior therapy (range, 2-5). Six of 7 pts had poor-risk features of del(17p), TP53 mutations, or both. Three of 7 pts had bulky disease. No DLTs occurred at 24 or 48 mg. The most common treatment-emergent AEs (>30%) were CRS (100%), fatigue (71%), injection-site reaction (43%), and nausea (43%). All pts experienced CRS in the first cycle, but no CRS events were higher than grade 2. No cases of ICANS were observed. TLS was not observed. Antileukemic activity has been observed at both dose levels, with partial responses in 3 of 5 pts. Updated clinical and pharmacokinetic data, including data for additional pts treated with epcoritamab, will be presented. Conclusions: These data suggest that epcoritamab is well tolerated in pts with R/R CLL at dose levels up to 48 mg and has clinical activity in pts with high-risk features. The expansion part of this study in pts with R/R CLL and Richter syndrome will open later this year. Disclosures Kater: Janssen, AstraZeneca: Other: Ad Board, steering committee, Research Funding; BMS, Roche/Genentech: Other: Ad Board, , Research Funding; Genmab, LAVA: Other: Ad Board, Steering Committee; Abbvie: Honoraria, Other: Ad Board, Research Funding. Niemann: CSL Behring, Genmab, Takeda, Octapharma: Consultancy; Abbvie, AstraZeneca, Janssen: Consultancy, Research Funding; Novo Nordisk Foundation: Research Funding. Hutchings: Roche: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Novartis: Research Funding; Incyte: Research Funding; Janssen: Honoraria, Research Funding; Genmab: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; Genentech: Honoraria, Research Funding. Chen: Genmab: Current Employment. Rios: Genmab: Current Employment. Palenski: AbbVie: Current Employment. Li: Genmab: Current Employment. Mato: AbbVie: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; MSKCC: Current Employment; Genmab: Research Funding; Johnson and Johnson: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; LOXO: Consultancy, Research Funding; Nurix: Research Funding; DTRM BioPharma: Consultancy, Research Funding; TG Therapeutics: Consultancy, Other: DSMB, Research Funding; BeiGene: Consultancy, Research Funding; Acerta/AstraZeneca: Consultancy, Research Funding; AstraZeneca: Consultancy; Sunesis: Consultancy, Research Funding.

Characterization and Management of Oral and Dermatological Toxicities in Patients Receiving the CD3 X GPRC5D Bispecific Antibody Talquetamab (JNJ-64407564) for the Treatment of Relapsed and/or Refractory Multiple Myeloma

Background: Talquetamab (JNJ-64407564) is a humanized IgG4 bispecific antibody that targets the CD3 receptor complex on T cells and G-protein-coupled receptor class 5 member D (GPRC5D) a transmembrane receptor protein overexpressed on malignant plasma cells in Multiple Myeloma. After 6.3 months of follow up in RRMM, talquetemab monotherapy at the recommended phase 2 dose yielded an overall response rate of 70%. Talquetemab was well tolerated and here we describe the presentation and management of dermatologic and oral adverse events (AEs) in 78 patients (pts) treated with talquetemab at a single center that is part of a multi-center, multi-national study. Methods: Eligible pts with RRMM were enrolled to the Phase 1, first in human, open-label dose escalation study (NCT03399799) at our site, and received talquetamab intravenously (IV; range 1.5µg/kg -1200µg/kg biweekly or weekly) or subcutaneously (SC; 5µg/kg to 800µg/kg weekly). AEs were graded using CTCAE v4.03. Results: As of July 2021, 78 pts received talquetamab, 53 (67.9%) by IV and 25 (32%) by SC route. Treatment emergent dermatologic AEs were observed in 20 (25.6%) pts. The most common AEs were palmar/plantar desquamation in 22 pts (28.2%, grade 1/2), nail disorders in 14 pts (17.9%, all grade 1), systemic rash in 11 patients (14%, grades 1-3), and injection site reaction in 7 pts (8.9%, all grade 1). Time of onset for dermatologic toxicities was generally within the first 30 days of therapy. In collaboration with dermatology consultation, the management of palmar/plantar desquamation, nail disorders, and injection site reaction has been ammonium lactate 12% cream, triamcinolone 0.1% cream, along with plain Vaseline and Vanicream products applied twice daily. Of the 11 pts with systemic rash, 10 were at or above a dose of 405 µg /kg. Five pts had grade 3 rash requiring dose hold and systemic steroids in conjunction with topical medications. All pts have resumed dosing without recurrence of grade 3 rash. Four of these pts were at a dose level of 800 µg/kg SC. Grade 1-2 rash did not require dose hold and was managed with early intervention of the 3 topical treatments applied to affected areas twice daily. In addition to the above described dermatologic AEs, treatment emergent oral AEs were observed in 38 (48.7%) pts, all grade 1-2. 42 pts developed dysgeusia (53.8%), 16 developed dry mouth (20.5%), and 17 developed dysphagia (21.8% ). Dysgeusia resulted in 3 pts requiring drug interruption. 1 pt requiring dose reduction, and 1 discontinued treatment. The average time to onset for dysgeusia was 26.5 days. Dry mouth resulted in no drug interruptions, reductions, or discontinuations, and had an average onset of 6.7 days. Dysphagia also ranged from grades 1-2, with 3 pts requiring drug interruption. There were no dose reductions or treatment discontinuation. The average time to onset was 41.5 days. Dry mouth, dysgeusia, and dysphagia were more prevalent with higher doses. Along with GI and nutrition consultation, oral AEs have been successfully managed with saliva substitute sprays and rinses. These supportive interventions are instituted promptly at time of onset of symptoms. The above-described treatments for dermatologic and oral AEs were not protocol mandated procedures. Discussion The dermatologic and oral AEs associated with talquetamab have unknown etiologies and are currently under investigation. These AEs are typically low grade, rarely require dose holds or modifications, and have been manageable with early and consistent supportive care. Only one patient to date at our center, has discontinued treatment due to an oral or dermatologic side effect. Talquetamab appears to have a have favorable risk/benefit profile in RRMM with durable responses and manageable toxicities. A standardized regimen of topical and oral supportive care appears to be beneficial in the management of dermatological and oral side effects. Disclosures Farrell: Regeneron: Current Employment. Florendo: Legend Biotech: Current Employment. Catamero: Celgene: Ended employment in the past 24 months, Honoraria; Legend: Honoraria; Oncopeptides: Speakers Bureau. Parekh: Foundation Medicine Inc: Consultancy; Amgen: Research Funding; PFIZER: Research Funding; CELGENE: Research Funding; Karyopharm Inv: Research Funding. Richter: Janssen: Speakers Bureau; Celgene: Speakers Bureau; Adaptive Biotechnologies: Speakers Bureau; Celgene: Consultancy; Janssen: Consultancy; BMS: Consultancy; Karyopharm: Consultancy; Antengene: Consultancy; Sanofi: Consultancy; X4 Pharmaceuticals: Consultancy; Oncopeptides: Consultancy; Adaptive Biotechnologies: Consultancy; Secura Bio: Consultancy; Astra Zeneca: Consultancy. Chari: Janssen Pharmaceuticals: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Novartis Pharmaceuticals: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Consultancy, Research Funding; Takeda Pharmaceutical Company: Consultancy, Research Funding; Karyopharm: Consultancy; Sanofi Genzyme: Consultancy; Oncopeptides: Consultancy; Antegene: Consultancy; Glaxosmithkline: Consultancy; Secura Bio: Consultancy.

877. North American Phase 3/3b Experience with Long-Acting Cabotegravir and Rilpivirine: Efficacy, Safety, and Virologic Outcomes

Background Cabotegravir (CAB) plus rilpivirine (RPV) is the first complete long-acting (LA) regimen recommended by treatment guidelines for the maintenance of HIV-1 virologic suppression. CAB+RPV LA dosed every 4 weeks (Q4W) or every 8 weeks (Q8W) demonstrated noninferior efficacy in multinational Phase 3/3b trials. This post hoc descriptive analysis summarizes efficacy, virologic outcomes, safety, and treatment preference for US and Canadian (CAN) participants through Week (W) 48. Methods This analysis focuses on data for US/CAN participants naive to CAB+RPV (n=376) from the larger pooled population of the ATLAS, FLAIR, and ATLAS-2M Phase 3/3b studies (N=1245). Endpoints included the proportion of participants with plasma HIV-1 RNA ≥ 50 and < 50 c/mL at W48 (FDA Snapshot algorithm), incidence of confirmed virologic failure (CVF; 2 consecutive HIV-1 RNA ≥ 200 c/mL), safety, and treatment preference through W48. Results 376 US/CAN participants received CAB+RPV LA Q4W or Q8W. Median (range) age was 39y (20–74); 14.9% were female, 66.0% were White. At W48, 93.1% (350/376) maintained virologic suppression (HIV-1 RNA < 50 c/mL), 1.9% (7/376) had HIV-1 RNA ≥ 50 c/mL, and 0.8% (3/376) met the CVF criterion, consistent with the overall global pooled population (Table 1). Two of the three participants with CVF had ≥ 2 of the three baseline factors (archived RPV resistance-associated mutations [RAMs], HIV subtype A6/A1, body mass index [BMI] ≥ 30 kg/m2) previously associated with CVF. Among the US/CAN participants with a single baseline factor, none met CVF. Overall, archived RPV RAMs were observed in 3.2% (12/376), HIV subtype A6/A1 in 1.1% (4/376), and BMI ≥ 30 kg/m2 in 26.3% (99/376) of participants. Safety and injection site reaction findings were similar to the overall pooled population (Table 2). Most participants (120/134, 89.6%) preferred LA over oral dosing (7/134, 5.2%). Table 1. Snapshot outcomes following CAB+RPV LA Q4W and Q8W at Week 48 in participants naive to CAB+RPV from ATLAS, FLAIR, and ATLAS-2M (ITT-E population) Table 2. Safety summary through Week 48 following CAB+RPV LA Q4W and Q8W or comparator ART in participants naive to CAB+RPV from ATLAS, FLAIR, and ATLAS-2M Conclusion In US/CAN Phase 3/3b trial participants, CAB+RPV LA was highly effective and well tolerated, with outcomes consistent with the overall pooled population. Baseline prevalence of archived RPV RAMs and subtype A6/A1 was low and aligned with regional prevalence/surveillance data. CAB+RPV LA provides a tolerable and effective injectable LA treatment option for virologically suppressed US/CAN individuals with HIV. Disclosures Babafemi O. Taiwo, MBBS, Gilead (Consultant)Merck (Consultant)ViiV Healthcare (Consultant) Darrell Tan, MD PhD, Abbvie (Grant/Research Support)Gilead (Grant/Research Support)GlaxoSmithKline (Scientific Research Study Investigator)ViiV Healthcare (Grant/Research Support) Parul Patel, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Paula Teichner, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Joseph Polli, PhD, FAAPS, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Louise Garside, PhD, GlaxoSmithKline (Employee) Ronald D’Amico, DO, MSc, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Christine L. Talarico, M.S., GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Rodica Van Solingen-Ristea, MD, Janssen Research and Development (Employee)ViiV Healthcare (Employee) Bryan Baugh, MD, Janssen, Johnson & Johnson (Employee, Shareholder) William Spreen, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Michael Aboud, MBChB, MRCP, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Matthew Bosse, DO, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee)

Invaluable role of histopathology in the diagnosis of cutaneous leiomyosarcoma in insulin injection site reaction

Soft tissue sarcomas (STSs) are rare and may often be misdiagnosed, resulting in delays in treatment. A 67-year-old cisgender woman with type 2 diabetes mellitus and obesity presented to her primary care physician with a mass on her left proximal arm. The clinical opinion of the attending physician was that of an insulin injection site reaction. After further evaluation from the physician, the patient was diagnosed with a lipoma without confirmatory histology. The patient continued to present with an enlarging mass, decline in health status and continued with local wound care. The patient underwent a confirmatory biopsy following which, the patient was diagnosed with leiomyosarcoma. This case report highlights the case of a person with a low or moderate income with a self-reported low health literacy living in a rural community and how STS may be misdiagnosed in medically underserved. The patient’s primary or oncology care team are not involved in the production or review of this case report.

Delayed injection site reaction after mRNA-1273 vaccination in Japan: a retrospective, cross-sectional study

The incidence of delayed injection site reaction after the first dose of mRNA-1273 was 12.5% among females and 1.5% among males in a cohort of primarily elderly Japanese. After the second dose, 48.4% of those who could be contacted reported recurrence. The reaction may be relatively common among Asian females.