Zanubrutinib (Brukinsa)

CADTH recommends that Brukinsa be reimbursed by public drug plans for the treatment of adult patients with relapsed or refractory Waldenström macroglobulinemia (WM), if certain conditions are met. Brukinsa should only be covered to treat patients with relapsed or refractory WM who have received at least 1 prior line of therapy, meet at least 1 criterion for treatment according to International Workshop on WM (IWWM) consensus panel criteria, and have good performance status. Patients eligible for reimbursement of Brukinsa should not have disease transformation, which is WM that has transformed into another type of cancer, or received prior treatment with a drug of the same class (i.e., a Bruton tyrosine kinase [BTK] inhibitor) unless such therapy was stopped because the drug was not tolerated and the disease had not progressed. Brukinsa should only be reimbursed if prescribed by a clinician with expertise and experience in the treatment of WM and monitoring of therapy and if it does not cost more than other treatments for WM.

Histopathology-guided management of ocular surface squamous neoplasia with corneal stromal or scleral invasion using ruthenium-106 plaque brachytherapy

Background/aimTo evaluate the safety and efficacy of ruthenium-106 (Ru-106) plaque brachytherapy in managing invasive ocular surface squamous neoplasia (OSSN).MethodsThis is a retrospective, non-comparative, interventional case series of 42 eyes with OSSN with histopathologically-proven corneal stromal and/or scleral invasion that underwent Ru-106 plaque brachytherapy. Main outcome measures were tumour regression, eye salvage, final visual acuity, treatment complications and metastasis.ResultsAt presentation, the mean tumour basal diameter was 9.3 mm (range 5–26 mm) and thickness 3.1 mm (range 1.5–11 mm). Prior treatment included excision biopsy in two patients (5%), incision biopsy and topical interferon in one each (2%). Following excision with 4 mm clinically clear margins, corneal stromal and/or scleral invasion of OSSN was confirmed in all 42 cases, with the excised base showing invasive squamous cell carcinoma. A total dose of 5000 cGy over a mean duration of 19.7 hours (range 7–41 hours) was provided to an axial depth of 2 mm using Ru-106 surface plaque. Over a mean follow-up of 36.9 months (range 22.3–72 months), complete tumour regression was achieved in all eyes (100%). Two eyes (5%) showed conjunctival tumour growth remote from the site of prior treatment. Visual acuity was maintained at ≥20/200 in 35 eyes (83%), with a loss of >2 Snellen lines in 1 eye (2%). There was no evidence of regional lymph node or systemic metastasis.ConclusionHistopathology-guided use of Ru-106 surface plaque brachytherapy is a safe and an effective adjuvant therapy in the management of corneal stromal and/or scleral invasion of OSSN.

Impact of the line of treatment on progression-free survival in patients treated with T-DM1 for metastatic breast cancer

Background Trastuzumab emtansine (T-DM1) is indicated as second-line treatment for human epidermal growth factor receptor 2 (HER2)-positive metastatic or unresectable locally advanced breast cancer, after progression on trastuzumab and a taxane-based chemotherapy. We wished to determine if the line of treatment in which T-DM1 is administered has an impact on progression-free survival (PFS) and in particular, if prior treatment with capecitabine/lapatinib or pertuzumab modifies PFS of further treatment with T-DM1. Patients and methods We performed a multicenter retrospective study in 3 Belgian institutions. We evaluated PFS with T-DM1 in patients treated for HER2 positive metastatic or locally advanced unresectable breast cancer between January 1, 2009 and December 31, 2016. Results We included 51 patients. The median PFS was 9.01 months. The line of treatment in which T-DM1 (1st line, 2nd line, 3rd line or 4+ lines) was administered had no influence on PFS (hazard ratio 0.979, CI95: 0.835–1.143). There was no significant difference in PFS whether or not patients had received prior treatment with capecitabine/lapatinib (9.17 vs 5.56 months, p-value 0.875). But, patients who received pertuzumab before T-DM1 tended to exhibit a shorter PFS (3.55 months for T-DM1 after pertuzumab vs 9.50 months for T-DM1 without pretreatment with pertuzumab), even if this difference was not statistically significant (p-value 0.144). Conclusion Unlike with conventional chemotherapy, the line of treatment in which T-DM1 is administered does not influence PFS in our cohort of patients with advanced HER2-positive breast cancer.

Real-World Assessment of Prior Treatment Patterns in Patients Receiving Belantamab Mafodotin Using a Longitudinal Pharmacy and Medical Open Source Claims Database

Introduction: Belantamab mafodotin (belamaf) is a first-in-class B-cell maturation antigen-targeting antibody-drug conjugate, with a manageable adverse event profile, that has shown durable efficacy in a broad range of patients with relapsed or refractory multiple myeloma (RRMM) (Lonial et al., Lancet Oncol. 2020). As belamaf is an approved therapy, it is important to understand how it is being integrated into the management of patients with RRMM. The aim of this analysis was to examine baseline demographic and treatment patterns of these patients prior to belamaf in a real-world clinical practice. Methods: This descriptive, retrospective cohort study used IQVIA's longitudinal pharmacy and medical open source claims database, a nationally representative real-world database. The study covered the period from January 2001 to April 2021. Patient inclusion into the study required belamaf treatment initiation and ≥18 years of age at initiation. The first claim date for belamaf during the index period (August 2020 to April 2021) was the index date (ID). Key measures included patient demographics and prior MM treatments. Patient demographics were identified at the ID. Prior MM treatments were assessed during the prior treatment period, which extended from the database start date (January 2001) until the ID. The definition of a line of therapy (LOT) used in this analysis was consistent with published guidance (Rajkumar SV, et al. Blood, 2015;126:921-922). Treatments of interest were identified within the first 28 days of the first observed claim for MM treatment. A new LOT was identified if a new treatment was added after the initial 28 days after the start of the LOT, ≥1 treatment was discontinued (defined by a coverage gap >60 days), or the same LOT was restarted at a later date if ≥1 regimen was administered in between. Different therapeutic classes (e.g. PIs, immunomodulatory drugs, anti-CD38 antibodies) could be used in each LOT either singly or in combinations. Addition/deletion of corticosteriods did not constitute a new LOT. Results: 304 patients with a claim for belamaf were identified in the database and included in the analysis; median age was 70 years and 50.3% were female. Median (range) time from the earliest observed claim for MM treatment during the prior treatment period to the ID was 1,812 (104─6,676) days. Median (range) time from the earliest observed diagnosis for MM during the prior treatment period to the ID was 2,123 (22-7,186) days (~5.8 years). The median number of MM therapeutic classes, overall, received during the prior treatment period was 5; 82.9% of patients with MM received ≥4 classes of MM therapy. Prior therapy for MM was observed for 303 patients; the therapeutic classes of those MM treatments are shown in the Table. The median number of observed LOTs received by patients in the prior treatment period was 5 and 73.0% had ≥4 LOTs. LOT for belamaf may be over/under estimated as reporting on some of the MM medications was embargoed by manufacturers and/or specialty pharmacies for certain periods of time, leading to some incompleteness of data. Embargoed products included lenalidomide, pomalidomide, selinexor, thalidomide, ixazomib, and bortezomib. Although data capture for these MM treatments may not be complete in open source claims, some of the claims data for these medications were included in this analysis, i.e., medical claims for infused medications and pharmacy claims from switch suppliers for oral medications. Conclusions: The real-world evidence analyzed in this study is in line with the baseline characteristics reported for the DREAMM-1 and DREAMM-2 trials (Lonial et al., Lancet Oncol. 2020, Trudel et al., Blood Cancer J., 2019). Patients receiving belamaf have triple-class refractory myeloma with multiple LOTs generally aligned with the current indication. The most frequent prior treatments included proteasome inhibitors, anti-CD38 monoclonal antibodies, immunomodulatory drugs, and corticosteroids. Corticosteroid use is high as it is required to be prescribed in combination with other drugs according to their indications. This study identified patients in the US receiving belamaf and provides early insights into the patient demographic and clinical characteristics as well as number and range of treatments prior to treatment with belamaf. Funding: GSK (Study 214283). Figure 1 Figure 1. Disclosures Boytsov: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Stockl: IQVIA: Current Employment; GlaxoSmithKline: Research Funding. Chen: GlaxoSmithKline: Research Funding; IQVIA: Current Employment. Wang: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Wang: IQVIA: Current Employment; GlaxoSmithKline: Research Funding. Cao: IQVIA: Current Employment. Doherty: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Paka: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company.

Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome without Hematopoietic Cell Transplantation in a Real-World Population in the United States: Patient Characteristics, Prior Treatment Patterns, and Time to Diagnosis

Introduction: Sinusoidal obstruction syndrome (SOS), also known as hepatic veno-occlusive disease (VOD), is a rare form of hepatic injury where liver veins are blocked by damaged endothelial cells (Hildebrandt GC, et al. Br J Haematol. 2020;190:508-19). It is often associated with chemotherapy and radiation therapy given before a hematopoietic cell transplantation (HCT) but may occur outside of the HCT setting (Richardson PG, et al. Expert Rev Clin Pharm. 2018;11:113-24). The most severe form of VOD/SOS is associated with multiorgan dysfunction/multiorgan failure (MOD/MOF) and has a mortality rate of >80% if untreated (Coppell JA, et al. Biol Blood Marrow Transplant. 2018:53:138-45). This study describes the characteristics of VOD/SOS that occurs outside of the HCT setting (non-HCT VOD/SOS) in patients in the United States (US). Methods: This retrospective real-world evidence (RWE) study identified patient records within the TriNetX Dataworks US Network Electronic Medical Records (EMR) database, which covers 67 million patients from 44 healthcare organizations. Inclusion criteria required that patients had ≥1 record of a VOD/SOS diagnosis (ICD-10 code: K76.5) between January 1, 2016 and December 31, 2020, had received ≥1 instance of chemotherapy, antibody drug conjugates (ADC), or radiotherapy within 100 days prior to their first recorded VOD/SOS diagnosis, and had no record of HCT during the study period. Patient demographics and clinical characteristics, prior treatment regimen, and time to VOD/SOS diagnosis were characterized using descriptive statistics. Index treatment was defined as the treatment taken in the 100 days prior to VOD/SOS diagnosis, determined by the following hierarchy list of therapies: radiotherapy, gemtuzumab ozogamicin (GO)/inotuzumab ozogamicin (INO), vincristine, cytarabine, oxaliplatin-based, thioguanine, cyclophosphamide, 5-fluorouracil-based, etoposide, daunorubicin, doxorubicin, PEG-L-asparaginase, fludarabine, actinomycin-D, and other chemotherapies. Results: Of the 67 million patients available in the TriNetX database, 614 patients had documented VOD/SOS during the study period. Of those, 542 had ≥1 record in the EMR prior to the first VOD/SOS diagnosis. Among these 542 cases, 419 (77%) were non-HCT-related (did not have a record of HCT in the entire study period); the other 123 (23%) had a record of HCT (Figure 1). Of the 419 non-HCT VOD/SOS patients, 183 (44%) had ≥1 record of chemotherapy, ADC, or radiotherapy within the 100 days prior to first VOD/SOS diagnosis and comprised the study population. Among those 183 patients, 73 (40%) had a diagnosis of MOD/MOF at the same time VOD/SOS was documented; 61 (33%) were pediatric patients (≤16 years of age). Hematologic malignancies were the most common underlying condition (Table 1). A few patients had prior treatment with GO or INO (1% and 3%, respectively). The top 5 most common chemotherapies administered included cytarabine (25%), cyclophosphamide (20%), vincristine (17%), fludarabine (12%), and doxorubicin (11%). Overall, 103 (56%) non-HCT patients had a VOD/SOS diagnosis ≤21 days from index treatment. The median time from index treatment to VOD/SOS diagnosis was 13 days (interquartile range [IQR]: 1, 43 days) among all 183 patients. Among patients without MOD/MOF, median time was 18 days (IQR: 2, 44 days) and among patients with MOD/MOF, median time was 9 days (IQR: 0, 34 days). Conclusions: In this retrospective RWE study, the number of patients diagnosed with VOD/SOS outside of the HCT setting was approximately 3 times higher than those diagnosed in the HCT setting. Less than half of the patients diagnosed with non-HCT VOD/SOS had prior chemotherapy, ADC, or radiotherapy. Many of the non-HCT VOD/SOS patients were diagnosed with MOD/MOF. Among patients with non-HCT VOD/SOS, approximately half received their last dose of chemotherapy/ADC/radiotherapy >21 days before VOD/SOS diagnosis. Study limitations included those inherent to a retrospective study, the absence of availability of chemotherapy dosing in the database, and inability to detect misdiagnosis or under-diagnosis of VOD/SOS (which may result in under-estimation of the true number of VOD/SOS cases). The unexpected, relatively high number of VOD/SOS cases in the non-HCT setting, compared to the post-HCT setting, demonstrates a substantial unmet need, as there is no VOD/SOS treatment currently indicated for these patients. Figure 1 Figure 1. Disclosures Wang: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Benettaib: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Ni: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Jin: TriNetX: Current Employment. Kuranz: Apellis Pharmaceuticals, Inc.: Other: Payments from Apellis Pharmaceuticals to my institution TriNetX; TriNetX: Current Employment. Amber: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Ben-Joseph: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company.

ITVT-05. Intraoperative Ultrasound Guidance Improves Resection In Gliomas – Results From A Single Centre Propensity Matched Comparative Cohort Analysis Of 2D Vs Navigated 3D Ultrasound In 500 Gliomas

INTRODUCTION Intraoperative ultrasound (iUS) is a promising tool for glioma surgery. Navigated 3-D (n3D) iUS has many benefits over standard 2-D iUS. METHODS This was a retrospective comparative cohort study using propensity score matching (PSM). 500 consecutive histologically confirmed gliomas were divided into 2 cohorts – 2DiUS - Cohort A; and n3DiUS -Cohort B. PSM was used to account for known confounders (250 in each group; 1:1 matching). Gross total resection rates (based on iUS findings as well as postoperative MR) and perioperative morbidity were analyzed across the groups as were factors influencing these outcomes (using univariate as well as multivariate regression models). RESULTS Overall, the majority of the patients were adults (94%), males (71%) with hemispheric tumors (96%). 35% had tumors close to eloquent regions and 23% had received some prior treatment. The majority were high-grade gliomas (85%). 2D iUS was employed mainly for localization (80%) whereas n3D was used predominantly for resection control (84%) [p < 0.001]. GTR rate was higher in the n3D cohort (55.2% vs 38.4% in 2D; p = 0.001). The odds of having a complete resection in the n3D cohort was twice that of the 2D. Prior treatment, hemispheric location, and use of fluorescence were also significantly associated with higher GTR rates on univariate analysis. On multivariate analysis, all of these remained significant. There was no difference in the morbidity rates in the two cohorts. N3D iUS had a higher specificity and positive likelihood ratio in detecting tumor residue. CONCLUSION For hemispheric gliomas undergoing resective surgery, the use of navigated 3D ultrasound improves GTR rates, with no added morbidity. It is more likely to be used for resection control mode than is 2DUS and this is probably because n3DUS is more specific and likely to pick up tumor residues contributing to its better accuracy.

Attenuation of the Airway and Cardiovascular Responses to Extubation in Chronic Smokers by Prior Treatment with Dexmedetomidine, Fentanyl, and their Combination

BACKGROUND: Respiratory complications and hemodynamic changes during and after extubation are more common than during tracheal intubation and induction of anesthesia. AIM: The objective of this study was to compare the efficacy of prior treatment with dexmedetomidine, fentanyl, and their combination on the attenuation of the airway and cardiovascular responses to extubation. METHODS: The subjects were adult chronic male smokers, representing the population in which secondary response to extubation is most common. A randomized double-blinded comparative trial was conducted on 66 patients who were 20–60 years of age, chronic male smokers, scheduled for elective surgeries, and divided into three equal groups according to given drug 20 min before the end of surgery. Group A (n = 22) received 1 ug. kg−1 dexmedetomidine, Group B (n = 22) received fentanyl 1 ug. kg−1, and Group C (n = 22) received a mixture of the previously used drugs in the same doses. Time to and quality of extubation, airway and hemodynamic responses, and post-operative agitation and sedation were recorded. RESULTS: Hemodynamic responses and quality of extubation were better in both Groups A and C than patients in Group B at the expense of increasing time to extubation, post-extubation sedation, and delayed recovery in Group C. CONCLUSION: Single-dose dexmedetomidine 1 ug. kg-1 given 15 min before extubation in chronic cigarette smokers provided better attenuation of the airway and cardiovascular responses to extubation and suctioning with better recovery profile when compared to fentanyl 1 ug. kg-1 and dexmedetomidine mixed with fentanyl in the same previous doses.