Practical guidelines for monitoring and management of coagulopathy following tisagenlecleucel CAR T-cell therapy

Cytokine release syndrome (CRS) is a systemic inflammatory response associated with chimeric antigen receptor T-cell (CAR-T) therapies. In severe cases, CRS can be associated with coagulopathy and hypofibrinogenemia. We present our global multicenter experience with CRS-associated coagulopathy after tisagenlecleucel therapy in 137 patients with relapsed or refractory B-cell acute lymphoblastic leukemia from the ELIANA and ENSIGN trials. These trials included clinical guidelines for fibrinogen replacement during CRS-associated coagulopathy. Hypofibrinogenemia requiring replacement was observed only in patients with severe CRS. A higher percentage of patients who required replacement were <10 years old, compared with those who did not require replacement. Twenty-three patients received replacement for hypofibrinogenemia (<1.5 g/L); 9 of them developed marked hypofibrinogenemia (<1 g/L). Very low fibrinogen levels (<1 g/L) were documented in patients before maximal CRS (n = 1), during maximal CRS (n = 7), and at CRS improvement (n = 1). Although hypofibrinogenemia was the most clinically significant coagulopathy, some patients also developed prolonged prothrombin time and activated partial thromboplastin time and increased international normalized ratio, further increasing the risk of bleeding. Hypofibrinogenemia was effectively managed using fibrinogen concentrate or cryoprecipitate replacement; severe (grade 4) bleeding events were rare (n = 2). CRS-associated coagulopathy with hypofibrinogenemia is manageable according to empiric guidelines of fibrinogen replacement for CAR-T trials. Fibrinogen concentrate should be used when cryoprecipitate is not reliably available. Monitoring fibrinogen levels in patients with moderate or severe CRS is essential for avoiding potentially fatal bleeding events

Understanding the patient experience and treatment benefits in patients with non–small‐cell lung cancer with brain metastasis

Abstract Background Despite the high prevalence of brain metastases (BM) secondary to non–small‐cell lung cancer (NSCLC) (NSCLC/BM), patients' experiences (symptoms and impacts) are not fully understood. This study sought to understand the patient experience with NSCLC/BM and identify a patient‐reported outcome (PRO) measure fit to capture the most important NSCLC/BM symptoms and impacts. Methods A targeted literature review was completed; the National Comprehensive Cancer Network (NCCN)/Functional Assessment of Cancer Therapy–Brain Symptom Index, 24‐item version (NFBrSI‐24) was identified as a relevant measure that assessed the core symptoms and impacts associated with NSCLC/BM. Qualitative interviews composed of concept elicitation and cognitive debriefing with oncologists (n = 3) and adult patients (n = 16) with NSCLC/BM were conducted to confirm the content validity and evaluate the relevance and appropriateness of the NFBrSI‐24 for this condition. Results The NSCLC/BM symptoms and impacts identified in the literature and reported by oncologists and patients were consistent and captured in the NFBrSI‐24. Study participants reported significant burden associated with the symptoms (commonly fatigue, headache) and impacts of NSCLC/BM. Participants indicated that the NFBrSI‐24 captured their most salient experiences with NSCLC/BM and that symptom improvement or a delay in progression, as measured by the NFBrSI‐24, would be meaningful. During the cognitive debriefing, participants generally indicated that the NFBrSI‐24 was comprehensive and easy to understand/answer and that it assessed symptoms they considered most important to treat. Conclusions These results suggest that the NFBrSI‐24 adequately captures an appropriate measure of NSCLC/BM symptoms and impact

Patient-reported outcomes in capmatinib-treated patients with METex14-mutated advanced NSCLC: Results from the GEOMETRY mono-1 study

Introduction: Capmatinib, a MET inhibitor, showed substantial antitumour activity with manageable side effects in patients with MET exon 14 (METex14)-mutated advanced non-small cell lung cancer (aNSCLC) in the GEOMETRY mono-1 study. We report patient-reported outcomes (PROs) from this study. Methods: Enrolled treatment-naïve (1L) or pre-treated (2L+) patients with aNSCLC with a METex14-skipping mutation received 400 mg capmatinib twice daily during 21-day treatment cycles. PROs were collected at baseline and every six weeks thereafter using EORTC QLQ-C30 global health status/quality of life (GHS/QoL), QLQ-LC13 symptoms, and EQ-5D-5L visual analogue scale (VAS) questionnaires. Results: As of 6 January 2020, 27/28 1L and 65/69 2L+ patients had completed PROs at baseline; compliance rates remained >70%. Cough improved early, with meaningful improvements (≥10-point change from baseline) observed throughout cycles (mean change from baseline [SD] by week 7: 1L −13.0 [39.9], 2L+ −8.2 [28.4]; week 43: 1L −28.2 [26.7], 2L+ −10.5 [27.3]). QoL, assessed by GHS/QoL and VAS, improved by week 7 in 1L and 2L+ patients, with improvements generally sustained over time. Median time to definitive deterioration (TTDD) in GHS/QoL was 16.6 months (95% CI: 9.7, not estimable [NE]) in 1L and 12.4 months (95% CI: 4.2, 19.4) in 2L+ patients. Median TTDD for dyspnoea was 19.4 months (95% CI: 12.4, NE) and 22.1 months (95% CI: 9.9, NE) for 1L and 2L+ patients, respectively, and NE for cough and chest pain. Conclusions: Capmatinib was associated with clinically meaningful improvements in cough and preserved QoL, further supporting its use in patients with METex14-mutated aNSCLC. Trial registration: ClinicalTrials.gov registry number: NCT02414139