Search

A Japanese study published in Drugs - Real World Outcomes found that treatment with Janus Kinase (JAK) inhibitors is associated with deep vein thrombosis (DVT) and pulmonary embolism (PE). The study analyzed data from the Japanese Adverse Drug Event Report database and identified 6631 JAK inhibitor-related adverse events, including 60 cases of DVT and 41 cases of PE. The study detected a reporting odds ratio (ROR) signal for DVT and PE for certain JAK inhibitors, including baricitinib, upadacitinib, and tofacitinib. The authors concluded that caution should be exercised when using JAK inhibitors due to the risk of DVT and PE. [Extracted from the article]

A 45-year-old man with a history of bipolar disorder and chronic myeloid leukemia (CML) experienced a lack of efficacy with imatinib treatment and subsequently developed acute pancreatitis (AP) while being treated with nilotinib. The patient presented to the emergency unit with abdominal pain and nausea, and tests revealed elevated serum lipase and amylase levels. Abdominal ultrasonography showed a normal pancreas. The patient's treatment with nilotinib was discontinued, and he received fluid therapy and pain management. His symptoms resolved, and his lipase and amylase levels returned to normal. The adverse drug reaction was considered probable. [Extracted from the article]

Individual case safety reports (ICSRs) in the US FDA Adverse Event Reporting System (FAERS) up until September 2022 were used to evaluate psychiatric AEs reported in patients treated with nonselective RET MKIs including cabozantinib, lenvatinib, sorafenib, sunitinib and vandetanib. Nonselective RET (rearrangement during transfection) multikinase inhibitors (MKIs) used in the treatment of cancer are associated with psychiatric adverse events (AEs), according to findings of a study published in I Frontiers in Pharmacology i . Reported ADRs included aphonia, confusion, disorientation, eating disorders and change in mental status with sorafenib; aphonia, eating disorders, lethargy and hypersomnia with cabozantinib; eating disorders, mutism and thyrotoxic crisis with sunitinib; and eating disorders with lenvatinib. [Extracted from the article]

The risk of some cardiovascular toxicities, in particular pericarditis, may be increased in patients receiving anaplastic lymphoma kinase (ALK) inhibitors, according to a study conducted by researchers from Japan. "Careful monitoring of pericarditis is suggested when ALK inhibitors are administered, in addition to baseline examination considering the cardiovascular toxicity profile of each drug", conclude the researchers. The disproportionality analysis of adverse-event reports from 19 911 ALK inhibitors users showed that pericarditis signals were detected with all five ALK inhibitors, with reporting odds ratios (RORs) ranging from 3.5 (95% CI 1.33-9.46) for brigatinib to 12.9 (95% CI 9.37-17.79) for ceritinib. [Extracted from the article]

However, the patient who received baricitinib developed pulmonary thrombosis and the patient who received upadacitinib developed portal vein thrombosis. B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event In a retrospective, real-world, pharmacovigilance study, involving 11069800 patient reports conducted from food and drug administration's adverse event reporting system utilizing the data from 1 January 2012 to 30 September 2021, et al. patients [ I ages and sexes not stated i ] were described who developed pulmonary thrombosis during treatment with baricitinib or portal vein thrombosis during treatment with upadacitinib I [indications, routes, dosage, duration of treatment to reaction onset and outcomes not stated i ]. [Extracted from the article]

Adverse events in lymphoma patients treated with phosphoinositide 3 kinase Inhibitor in clinical trials: a meta-analysis Annals of Hematology: 13 Jun 2022. Treatment with phosphoinositide 3 kinase (PI3K) inhibitors in patients with lymphoma increases the risks of neutropenia, pneumonia and diarrhoea, according to findings of a meta-analysis published in I Annals of Hematology i . Meta-analysis found that treatment with copanlisib, duvelisib or idelalisib significantly increased the risk of all-grade AEs compared with non-PI3K inhibitors (risk ratio [RR] 0.95; 95% CI 0.92, 0.98) and the risk of high-grade AEs (RR 0.63; 95% CI 0.57, 0.70). [Extracted from the article]

Treatment with anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) may cause psychiatric adverse events (AEs) in patients with advanced ALK-rearranged non-small cell lung cancer (NSCLC), according to findings of a real-world pharmacovigilance study published in I Targeted Oncology i . Psychiatric AEs included mood disorders (39 cases), psychotic disorders (24), anxiety, agitation or irritability (25), sleep disorders, cognitive disorders, eating disorders, fear and panic attacks, and behavioural abnormalities. Data from spontaneous reports submitted to the US FDA Adverse Events Reporting System (FAERS) up until December 2020 were used to investigate psychiatric AEs in patients receiving ALK TKIs for NSCLC (alectinib, brigatinib, ceritinib, crizotinib or lorlatinib). [Extracted from the article]

Janus Kinase (JAK) Inhibitors in Rheumatoid Arthritis Patients: Risk of Major Adverse Cardiovascular Events (MACE) and Malignancies [Excluding Non-Melanoma Skin Cancer (NMSC)] Internet Document: 31 Dec 2021. Treatment with a Janus kinase (JAK) inhibitor (baricitinib, tofacitinib or upadacitinib) in patients with rheumatoid arthritis (RA) may increase the risk of major adverse cardiovascular events (MACE) and cancer, advises the Malaysian National Pharmaceutical Regulatory Agency (NPRA). [Extracted from the article]

FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions Internet Document: 1 Sep 2021. The US FDA is requiring new and updated safety warnings about an increased risk of major adverse cardiovascular events, cancer, thrombosis and mortality for the Janus kinase (JAK) inhibitors tofacitinib [Xeljianz, Xeljianx XR], baricitinib [Olumiant] and upadacitinib [Rinvoq]. [Extracted from the article]

Reporting rates were significantly elevated for baricitinib-related pulmonary embolism (ROR 12.23; 95% CI 8.35, 17.89) and DVT (ROR 14.84; 95% CI 9.64, 22.84); ruxolitinib-related portal vein thrombosis (ROR 4.16; 95% CI 2.70, 6.40) and thrombosis (ROR 1.40; 95% CI 1.20, 1.63); and tofacitinib-related pulmonary thrombosis (ROR 2.36; 95% CI 1.69, 3.31). Janus kinase inhibitor (JAKinib)-related thromboembolic events (TEs) are reported across indications, according to findings of an Arena Pharmaceuticals-funded study published in I Drug Safety i . The US FDA's Adverse Event Reporting System (FAERS) database was searched from January 2010 to September 2019 for cases of deep vein thrombosis (DVT), portal vein thrombosis, pulmonary thrombosis, thrombosis, venous thrombosis or pulmonary embolism reported for all FDA-approved JAKinibs (baricitinib, fedratinib, ruxolitinib, tofacitinib and upadacitinib) across indications including rheumatoid arthritis, ulcerative colitis, psoriasis, psoriatic arthritis, myelofibrosis and acute graft-versus-host disease. [Extracted from the article]

The woman was diagnosed with stage IV lung adenocarcinoma with multiple lung and bone metastases (cT4N3M1c). Thereafter, she underwent bronchoalveolar lavage (BAL) and a transbronchial lung biopsy through the right middle lobe bronchus (B5) and S8, respectively. B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event A 78-year-old woman developed interstitial lung disease (ILD) during treatment with osimertinib for lung adenocarcinoma. [Extracted from the article]

Imatinib-induced pancreatic hypertrophy in patients with gastrointestinal stromal tumor: Association with overall survival. B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event In a multi-centre retrospective study which included 48 patients with gastrointestinal stromal tumour who received imatinib between January 2004 and December 2019, a patient [ I age and sex not stated i ] was described, who developed pancreatic hypertrophy during treatment with imatinib for gastrointestinal stromal tumour. Subsequently, the patient developed pancreatic hypertrophy [ I duration of treatment to reaction onset not stated i ]. [Extracted from the article]

Upon presentation, a chest CT revealed mild bilateral pleural effusion and mild ground-glass opacities (GGOs) in the right lung. A chest CT revealed lung cancer invading the the carina, causing left lung atelectasis (advanced NSCLC). B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event A 60-year-old man developed interstitial pneumonitis during treatment with crizotinib and osimertinib for advanced non-small cell lung cancer (NSCLC) [ I routes not stated i ]. [Extracted from the article]

Next generation sequencing (NGS) with the biopsied tumour revealed epidermal growth factor receptor (EGFR) exon 21 L858R mutation with mutant allele fractions (MAF) of 24.8%. After nine months of icotinib therapy, MRI revealed multi-brain metastasis and enlarged right lung tumour. B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event A 59-year-old man exhibited drug resistance following treatment with osimertinib for non-small-cell lung cancer (NSCLC). [Extracted from the article]

On day 32 after treatment initiation, she developed erythematous papules on the anterior chest wall. B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event An 80-year-old woman developed toxic epidermal necrolysis (TEN) during treatment with osimertinib for adenocarcinoma stage-VIB. Five days after treatment discontinuation, she started treatment with oral prednisolone. [Extracted from the article]

B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event In a single center, retrospective study of 212 patients, who were treated with osimertinib at a Cancer Center In Japan between April 2016 and March 2020, 8 patients (7 women and 1 man) aged 39-73 years were described, who developed organising pneumonia or hypersensitivity pneumonia during treatment with osimertinib for EGFR-mutant non-small cell lung carcinoma (NSCLC). However, 1-7.7 months after the start of treatment, 8 patients developed interstitial lung disease (ILD) in the form of grade 1-2 organising pneumonia (3 patients) and hypersensitivity pneumonia (5 patients) associated with osimertinib use. Among 8 patients who underwent osimertinib re-challenge, only 1 patient with grade 2 ILD experienced relapse of ILD. [Extracted from the article]

The patient, who had NSCLC with epidermal growth factor receptor mutation (EGFR L858R) and without isocitrate dehydrogenases (IDH) mutation, received treatment with gefitinib. However, IDH1 R132C mutation appeared after osimertinib resistance [ I durations of treatments to reaction onset not stated i ] and the patient died in 2 months [ I cause of death not stated i ]. B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event In a study of 476 patients with non-small cell lung cancer (NSCLC) recruited between July 2016 and November 2019, a patient [ I age and sex not stated i ] was described, who developed drug resistance while receiving treatment with gefitinib and osimertinib for NSCLC [ I dosages and routes not stated i ]. [Extracted from the article]

She showed radiological stable disease (SD); however, a liquid biopsy (LB) after 6 months showed persistent EGFR-L858R mutation in the circulating free (cfDNA) cfDNA. The second re-biopsy showed persistent EGFR-L858R and T790M mutations in addition to a new I C797S i mutation in cis-position. EGFR-L858R NSCLC with Pleiotropic Resistance Mechanisms: T790M, C797S, SCLC-Transformation and KRAS, TP53, and BRAF Mutations. [Extracted from the article]

B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event A 22-year-old woman developed thrombocytopenia during treatment with imatinib for acute lymphoblastic leukaemia (ALL). Later, allogeneic peripheral blood stem cell transplantation was performed with post-transplant cyclophosphamide (PT-CY) from her HLA-identical sister. The dose of imatinib therapy was temporarily reduced to 200mg per day due to mild toxicity in the form of transient thrombocytopenia of 53 × 10 SP 9 sp /L [ I time to reaction onset not stated i ]. [Extracted from the article]

In May 2020, CT scan demonstrated bilateral enlargement of internal mammary lymph nodes and biopsy showed metastasis of neuroendocrine carcinoma characterised by medium and large cells, consistent with the diagnosis of LCNEC. B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event An 80-year-old man acquired resistance and experienced transformation of non-small cell lung cancer (NSCLC) to large-cell neuroendocrine carcinoma (LCNEC) during treatment with osimertinib. [Extracted from the article]

The patients had nonresectable non-small cell lung cancer with Exon 19 del gene mutation (n=88), Exon 19 dup (n=1) or L858R (n=34), which were identified during pre-treatment biopsies. B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event A retrospective study described 123 patients [ I ages and sexes not stated i ] with non-resectable non-small cell lung cancer, who received treatment with first or second generation tyrosine kinase inhibitors i.e. afatinib (55 patients), erlotinib (34 patients) or gefitinib (34 patients) across two hospitals in Germany and acquired resistance during the treatments [ I routes and dosages not stated i ]. [Extracted from the article]

Her TEN and immune-mediated pneumonitis were attributed to pembrolizumab and osimertinib. B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event A 72-year-old woman developed toxic epidermal necrolysis (TEN) and immune-mediated pneumonitis during treatment with pembrolizumab and osimertinib for non-small cell lung cancer. Eventually, a diagnosis of drug-induced immune-mediated pneumonitis was made. [Extracted from the article]

The RV biopsy revealed mild cardiomyocyte hypertrophy with infiltration of a few inflammatory cells in interstinum. B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event In a case report, 3 women aged 52-78 years were described, who developed cardiotoxicity in the form of decreased left ventricular ejection fraction (LVEF) and cardiomyocyte hypertrophy during treatment with osimertinib for advanced non-small cell lung cancer patients (NSCLC) [ I dosages and routes not stated; not all outcomes stated i ]. [Extracted from the article]

B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event A 68-year-old woman exhibited acquired drug resistance following treatment with osimertinib for EGFR positive lung adenocarcinoma with neuroendocrine differentiation. Additionally, she also exhibited lack of efficacy during treatment with paclitaxel for EGFR positive lung adenocarcinoma with neuroendocrine differentiation [ I routes not stated; not all dosages stated i ]. However, after 6 months of osimertinib treatment, gradual enlargement of lung lesions and bone lesions consistent with disease progression was noted. [Extracted from the article]

B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event An 84-year-old woman developed congestive heart failure, QTc prolongation and torsade de pointes following treatment with osimertinib for recurrent lung adenocarcinoma. She was diagnosed with congestive heart failure, QTc prolongation and torsade de pointes secondary to osimertinib therapy. [Extracted from the article]

B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event In a report, two women aged 21-year-old and 55-year-old were described, of whom the 21-year-old woman developed nausea, facial swelling, weight gain, hepatotoxicity, hypercholesterolaemia and skin toxicities including acneiform rashes and hyperpigmentation of the face skin during treatment with imatinib or nilotinib. However, she developed imatinib related adverse effects in the form of nausea, facial swelling and body weight gain, which led to long-term treatment interruptions. She was treated with unspecified statins, hepatoprotectors and antibacterial therapy for skin toxicities, but the side effects persisted (mainly acneiform rashes and hyperpigmentation). [Extracted from the article]

B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event In an observational, single-centre and retrospective study including patients receiving Janus kinase inhibitors (JAKi) for RA in the Rheumatology department of Amiens University Hospital between 1 October 2017 and 20 May 2020, four patients [ I ages and sexes not stated i ] were described, who exhibited inefficacy, treatment failure or developed digestive adverse effects during treatment with baricitinib and tofacitinib for rheumatoid arthritis (RA). The remaining one patient exhibited baricitinib treatment failure, whose tofacitinib treatment was continued until the data collection [ I duration of treatment to reaction onset not stated i ]. [Extracted from the article]

Six of the 24 patients developed grade 0-3 proteinuria related to the third-line treatment with everolimus (n=3; total dosage ranging from 140-620mg and treatment duration ranging from 2.1-3.2 months), pazopanib (n=2; total dosage ranging from 20 5800-38 4600mg and treatment duration ranging from 12.7-15.6 months) and sunitinib (n=1; total dosage 4025mg and treatment duration 7.1 months). Three of the 24 patients developed grade 2-3 proteinuria related to the sixth-line treatment with everolimus (n=1; total dosage 1235mg and treatment duration 9.7 months), axitinib (n=1; total dosage 518mg and treatment duration 5.3 months) and pazopanib (n=1; total dosage 6 4400mg and treatment duration 7.4 months). [Extracted from the article]

B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event An approximately 51-year-old man developed resistance during treatment with osimertinib for metastatic lung adenocarcinoma. Based on further investigations, he was diagnosed with lung adenocarcinoma with an EGFR exon 19 deletion mutation (EGFR 19del). Upon his re-examination on 05 August 2019, peritoneal, multiple liver and meningeal metastases of lung adenocarcinoma were considered. [Extracted from the article]

B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event A 48-year-old woman developed acquired resistance during treatment with osimertinib for lung adenocarcinoma [ I route and dosage not stated i ]. Subsequently, the lung adenocarcinoma progressed and her left lung tumour enlarged. A novel myh9-ret fusion occurrence and EGFR T790M loss as an acquired resistance mechanism to osimertinib in a patient with lung adenocarcinoma: A case report. [Extracted from the article]

B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event In a case report, 3 patients [including an 84-year-old woman; I not all ages and sexes stated i ] were described, of whom, one patient developed anorexia during treatment with osimertinib for cT4N3M1c stage IVB adenocarcinoma, and the remaining 2 patients exhibited no therapeutic response during treatment with gefitinib for non-small cell lung cancer [ I not all dosages and routes stated i ]. Case 2: The patient was diagnosed with non-small cell lung cancer (NSCLC) and was found to have L861Q mutation upon gene analysis. Case 3: The patient was diagnosed with non-small cell lung cancer (NSCLC) and was found to have L861Q mutation upon gene analysis. [Extracted from the article]

B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event A 45-year-old man developed resistance during treatment with icotinib and osimertinib for invasive stage IIIA lung adenocarcinoma with liver metastasis [ I routes not stated; not all dosages stated i ]. The man, who underwent a left upper lobectomy was found with invasive stage IIIA lung adenocarcinoma. Therefore, the fourth-line salvage therapy using nivolumab was prescribed, and the therapeutic efficacy was considerable, as evidenced by the decreased CEA, regressed mediastinal lymph nodes, reduced metastases in both left and right liver. [Extracted from the article]

B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event A 70-year-old man developed serositis during treatment with imatinib and hypertension, proteinuria and worsening of nephrotic syndrome that led to membranous nephropathy during treatment with sunitinib for gastrointestinal stromal tumours (GIST) [ I routes and dosages not stated; not all duration of treatments to reactions onset and outcomes stated i ]. The man, who had metastatic GIST, had received treatment with tyrosine kinase inhibitor imatinib for 2 years and then imatinib was replaced with sunitinib due to serositis. Laboratory investigations revealed urine protein to creatinine ratio (UPCR) of 20.76 mg/mg of creatinine and an elevated phospholipase A2 receptor (PLA2R) immunoglobulin G titer of 1:640 and proteinuria. [Extracted from the article]

B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event A 46-year-old woman developed acute liver failure during treatment with imatinib for gastrointestinal stromal tumour (GIST). Liver biopsy showed extensive inflammation of the liver parenchyma primarily comprised of neutrophils and a few lymphocytes with foci of parenchymal loss and bridging necrosis. Imatinib mesylate (Gleevec)-induced acute liver failure successfully treated with prednisolone therapy. [Extracted from the article]

B Author Information b An event is serious (based on the ICH definition) when the patient outcome is: * death * life-threatening * hospitalisation * disability * congenital anomaly * other medically important event A 65 year-old woman developed subdural-haematoma during treatment with imatinib for chronic myeloid leukemia (CML). However, a CT-scan of the head revealed left hemispheric and bilateral frontal acute/subacute subdural haematoma. A CASE OF SUBDURAL HEMATOMA IN A PATIENT WITH CHRONIC MYELOID LEUKEMIA TREATED WITH LOW DOSE IMATINIB MESYLATE. [Extracted from the article]

An assessment of the drug-drug interaction (DDI) potential of three Janus kinase inhibitors suggests a generally favourable disposition, according to results reported in I Drug Safety i , although as victim drugs baricitinib, tofacitinib and upadacitinib "show subtle pharmacokinetic differences that may be considered during polypharmacy". Assessment of the Janus kinase inhibitors as perpetrator drugs did not reveal any concerns from a DDI perspective. [Extracted from the article]

In a study of 5 patients, 3 patients including 2 adult men and a 71-year-old patient [not all ages and sexes stated] were described, who developed pleural effusion, abdominal cramps, muscle cramps, increased lipase level, increased amylase level, diffuse oedema and erectile deficit during treatment with dasatinib, imatinib and ponatinib for chronic myeloid leukaemia-chronic phase (CP-CML) [ I routes not stated; not all dosages, time to reactions onset and outcomes stated i ]. Patient 1: The adult man had a history of CML-CP, for which, he received ponatinib as third-line treatment at the age of 53 years. Patient 2: At the age of 71 years, the patient was diagnosed with accelerated-phase CML. [Extracted from the article]

Laboratory test performed 1 month post imatinib treatment were as follows: ALT 1058 U/L, AST 983 U/L, ALP 151 U/L and bilirubin total 1.9 mg/dL. Laboratory test performed 2 month post imatinib discontinuation were as follows: ALT 172 U/L, AST 114 U/L, ALP 246 U/L and bilirubin total 6.8 mg/dL. Laboratory test performed 6 month post imatinib discontinuation were as follows: ALT 42 U/L, AST 52 U/L, ALP 270 U/L and bilirubin total 5.7 mg/dL. [Extracted from the article]

In a study to assess the frequency of BCR-ABL gene mutations in 92 patients who had been treated with imatinib for more than 3 months, for chronic myeloid leukaemia (CML; the MAPTEST study) in Poland, three patients [1] were described [ I ages and sexes not stated i ], who acquired resistance to imatinib. One of these patients developed E255K mutation at the P-loop during the myeloid blastic crisis phase, another patient developed E255K mutation at the P-loop during the acceleration phase, whereas the remaining patient developed E355G mutation at the substrate-binding region during the acceleration phase. Frequency of BCR-ABL gene mutations in Polish patients with chronic myeloid leukemia treated with imatinib. [Extracted from the article]

At the time of interruption of tyrosine kinase inhibitors (TKI), the patient lost major molecular response to CML, but after re-starting TKI therapy, the patient showed response. During routine screening tests, serum amylase levels were found to be elevated (grade 1) and the pancreatic isozyme levels and serum lipase levels were within the normal limit. The influence of salivary amylase on total amylase elevation in CML patients treated with TKI therapy: a case series of 3 patients. [Extracted from the article]

According to the results of a systematic review and meta-analysis reported in I Gastroenterology i , the incidence of adverse events (AEs) in patients with immune-mediated diseases treated with Janus kinase (JAK) inhibitors is not increased, except for an increased risk of herpes zoster. The review included 82 studies with 66 159 patients, with 53, 11, 16 and 2 studies conducted in patients with rheumatoid arthritis, psoriasis, inflammatory bowel disease or ankylosing spondylitis, respectively. Safety of Janus Kinase Inhibitors in Patients with Inflammatory Bowel Diseases or Other Immune-mediated Diseases: a Systematic Review and Meta-Analysis. [Extracted from the article]

The patients received crizotinib for 3.6-57.8 months (13 patients) or lorlatinib for 4.1-19.1 months (3 patients). Of the 3 patients, who were receiving lorlatinib, 1 patient was found to have mutations including I ALK G1202R i and I ALK F1174L, i VAF 29% and 9%, respectively, which were observed during tumour biopsy. Acquired Resistance Mutations to ALK Inhibitors Identified by Single Circulating Tumor Cell Sequencing in ALK-Rearranged Non-Small-Cell Lung Cancer. [Extracted from the article]

A biopsy of the liver metastasis was done for I ALK i mutations in exons 22, 23 and 25, which revealed the presence of a G to A point mutation in exon 23 of the I ALK i gene that resulted in I G1202R i substitution of the I ALK i tyrosine kinase receptor. During further disease progression, her plasma was sent for circulating free tumour DNA (cfDNA) analysis, and the isolated cfDNA was tested for mutation hotspot regions in 12 genes ( I EGFR i , I ERBB2 i , I ALK i , I BRAF i , I KRAS i , I MAP2K1 i , I MET i , I NRAS i , I PIK3CA i , I ROS1 i , I RET i and I TP53 i ), along with I ALK i , I ROS1 i and I RET i rearrangements. In addition to this, cfDNA testing verified the ongoing presence of the I G1202R i mutation at a frequency of 14.5%, along with the subsistence of the variant 3a/b I EML4 i (6)- I ALK i (20) translocation. [Extracted from the article]

A 53-year-old woman developed bilateral pneumonia and cross-reactivity to anaplastic lymphoma kinase (ALK) inhibitors during treatment with brigatinib for lung adenocarcinoma. Chest X-ray demonstrated bilateral pulmonary infiltrates, which was confirmed by the chest CT scan. [Extracted from the article]

A study of 69 patients described 7 patients (including 4 women and 3 men) aged 51-81 years, who developed congestive heart failure, ischaemic stroke, ischaemic optic neuritis, atrial fibrillation, peripheral ischaemia or ST-elevation myocardial infarction (STEMI) during treatment with imatinib, nilotinib or ponatinib for chronic myeloid leukaemia (CML) [ I routes, dosages and outcomes not stated i ]. Age >60 yrs and the CV toxicity of new generation [tyrosine kinase inhibitors] are predisposing factors." A practical chart to evaluate the cardiovascular risk in chronic myeloid leukemia patients treated with Tyrosine Kinase inhibitors: A report from the Apulian Haematologists and Cardiologists Network. [Extracted from the article]

However, she developed periorbital swelling and pruritic maculopapular exanthema, which involved the trunk and extremities, within 10 days of the initiation of imatinib. B Author comment: b I "Patient had previously started imatinib 400 mg daily but within ten days she developed periorbital swelling and pruritic maculopapular exanthema involving her trunk and extremities." "The patient developed a similar rash within five days of initiation of an alternative tyrosine kinase inhibitor (nilotinib 50 mg/day).". [Extracted from the article]

Comprehensive genomic profiling (CGP) showed EML4-anaplastic lymphoma kinase (ALK) fusion and RICTOR amplification. Repeat CGP on pleural fluid showed EML4-ALK fusion along with secondary CTNNB1 p.S45V mutation and RICTOR copy gain. Subsequently, a fourth CGP was performed on a lung biopsy attained in December 2018, which showed EML4-ALK fusion with CTNNB1 p.S45 and RICTOR amplification along with a new tertiary ALK p.I1171N mutation. [Extracted from the article]

Subsequently, she started receiving dasatinib 50mg daily; however, she developed dyspnoea and productive cough, which led to the discontinuation of the dasatinib therapy. After three months of the treatment, she did not have any jaw pain and infection, and the osteonecrosis of the jaw improved to stage 1. B Author comment: b I "Unfortunately, patient was unable to tolerate numerous [protein-tyrosine kinase inhibitors] therapies.". [Extracted from the article]