6/20/2019 Disclosures Updates on Oncologic I have nothing to disclose Emergencies, Including Side Effects of New Therapies Gerald Hsu, MD, PhD Assoc. Clinical Professor of Medicine University of California, San Francisco Hypercalcemia | Old and new Outline • Mr. N: 72M with multiple myeloma. • Dx: 5/2015 in setting of long-standing MGUS • Updates on oncologic emergencies: (since 2003) Hypercalcemia • Prognostic info: IgG kappa, +lytic bone lesions, Tumor lysis syndrome Thrombocytopenia FISH without high-risk mutations Pleural effusions • Treatment: • 6/2015-10/2015: Velcade, cyclophosphamide, dexamethasone • Review of uses and side effects of immunotherapies • PR • 10/2015: Lenalidomide, dexamethasone • CR Progressive hip pain and diminished concentration. 1
6/20/2019 Hypercalcemia | Manifestations Ca 2+ ioniz Ca 2+ mg/dL mmol/L • Progressive mental 10.0 1.4 impairment and renal failure. Mild • A poor prognostic sign. 12.0 2.0 • Treatment is indicated if hypercalcemia is Moderate symptomatic or severe. 14.0 2.5 Severe Hypercalcemia | Mechanisms Hypercalcemia | Review type mechanism Associated cancers Humoral PTHrP • Squamous cancers (most volume repletion and supportive care commonly lung) - NS 200-300 cc/hr • Breast cancer • Renal cancer - oral phos repletion (goal 2.5-3 mg/dL) • Ovarian or endometrial cancer Osteolytic Cytokine mediated • Multiple Myeloma bring down the calcium and PTHrP • Breast cancer - bisphosphonate +/- calcitonin • Lymphoma - either pamidronate or zoledronate - response time: hours for calcitonin; about a day Much less common: • 1,25(OH) 2 D secreting tumors (lymphomas) with bisphophonate • PTH secreting tumors - duration: up to 4 weeks treat underlying cause 2
6/20/2019 Hypercalcemia | New(ish)! Outline Options for treating severe hypercalcemia in AKI (Cr >4.5) • Updates on oncologic emergencies: Hypercalcemia • Full dose bisphosphonate Tumor lysis syndrome Thrombocytopenia • Reduced dose bisphosphonate with slower Pleural effusions infusion rate • (eg. 4 mg zoledronic acid over 1 hour • Review of side effects of immunotherapies or 30 mg pamidronate over 4 hours) • Calcitonin until kidney function improves • RANK ligand inhibitor (ie. denosumab) that is not renally cleared. Tumor Lysis Syndrome | Old and New Tumor Lysis Syndrome | Review Definition: A syndrome resulting from “the metabolic • Mr. T: 70M with CLL with wbc count of derangements that occur with tumour breakdown following the initiation of cytotoxic therapy.” 150,000/uL, progressive anemia and bulky — Cairo & Bishop adenopathy. Laboratory tumor lysis = 2 or more electrolyte abnl • Prognostic info: FISH testing revealed } presence of deletion 17p. - K > 6 mEq/L - Phos > 4.5 mg/dL • Treatment: Considering ibrutinib or venetoclax or 25% change from baseline - UA > 8 mg/dL with or without rituximab. - Ca < 7 mg/dL Clinical tumor lysis = laboratory tumor lysis AND - Cr 1.5x ULN or - cardiac arrhythmia/sudden death or - seizure 3
6/20/2019 Tumor Lysis Syndrome | Review + new Tumor Lysis Syndrome | Review • Fluids 2-3 L/m2/day. (D5 1/4 NS preferable) • HIGH MEDIUM LOW • Hypouricemic agents allopurinol if uric acid is wnl • Burkitt CLL Multiple Myeloma Caution with patients of Asian descent (due to inheritance of HLA allele that • predisposes to severe cutaneous rxns) lymphoma/leukemia febuxostat (alternative to allopurinol) NHL with elevated LDH CML • rasburicase if high-risk or elevated uric acid in intermediate-risk High grade DLBCL • patients ALL (wbc <100K) Other solid tumors ALL (wbc >100K) exception is patients with G6PD deficiency • AML (wbc <100K) In practice, 3 mg dose is commonly used • AML (wbc >100K) small cell lung cancer • Monitoring CLL with high burden For patients at high-risk, serum K, Cr, Ca, Phos, uric acid, LDH q4- • disease + venetoclax germ cell tumors 8H (in addition to 4 hours after first rasburicase dose) Urine output (2 ml/kg/hr) • Thrombocytopenia | Review Outline • Mr. J: 54M with h/o hypertension, CKD, and sickle cell trait presents with 2 weeks abdominal pain, nausea, and vomiting. MEDS: EXAM: IMAGING: • Updates on oncologic emergencies: Atorvastatin -AF 192/130 116 -CT chest/abdomen Hypercalcemia Amlodipine -Lungs with bibasilar without acute findings. Tumor lysis syndrome Carvedilol crackles bilaterally. -U/S of kidneys with Thrombocytopenia Labetalol -Abd soft, NT, ND. moderate echogenicity Pleural effusions Pantoprazole -Neuro non-focal. bilaterally. Senna -Skin with petechiae. LABS: • Review of side effects of immunotherapies wbc 12.4 hb 7.9 plt 69 LDH 719 U (140-271) T bili 1.0 mg/dL (0.1-1.2) PT 14.2 s INR 1.1 PTT 31.4 s (wnl) Smear: “Few schistocytes with additional RBC fragments and blister cells. May be consistent with microangiopathic hemolytic anemia.” 4
6/20/2019 Thrombocytopenia | NEW! For TTP… DIC TTP abnl PT/PTT ADAMTS13 fibrinogen MAHA elev D-dimer low caplacizumab plt VTE PT arterial PTT thromb nl Median time to response: 2.7 days vs. 2.9 days 74% reduction in death, relapse, thromboembolic event +PF4 Ab Fewer days of plasma exchange +SRA Fewer days in hospital (9.9 vs. 14.4 days) HIT Pleural effusion Outline • Mr. T: 68M with CLL and new pleural effusion. •PET CT revealed fdg avid pleural nodules and • Updates on oncologic emergencies: hilar adenopathy. Hypercalcemia •Thoracentesis performed and cytology revealed Tumor lysis syndrome Thrombocytopenia atypical cells suspicious for adenocarcinoma Pleural effusions that is confirmed with additional staining. • Review of side effects of immunotherapies How should we manage the pleural effusion? 5
6/20/2019 Study question: Does talc administration through pleural catheter increase rates of pleurodesis compared with placement of catheter alone? Design: Randomized study. Primary outcome: Rates of pleurodesis. Secondary outcome: Quality of life. All-cause mortality. Duration of hospitalization. Complexity of pleural effusion. Number of therapeutic thoracenteses. N Engl J Med 378(14):1313-1322 April 5, 2018 Patients: 154 patients in the UK with malignant pleural effusions (from solid tumors) and a life expectancy of greater than 2 months. Outline Main finding: Talc group had higher rates of pleurodesis (43% vs. 23%; hazard ratio 2.2, p<0.008). • Updates on oncologic emergencies: Hypercalcemia Tumor lysis syndrome Other findings: Thrombocytopenia Pleural effusions -Talc group had significantly higher measures on quality of life assessments. • Review of side effects of immunotherapies -No significant difference in mortality or difference in number of days spent in hospital. 6
6/20/2019 Cancer cell Cancer cell 2014 Melanoma PD ligand-1 pembrolizumab 2015 Lung nivolumab Renal cell Immune cell 2016 Head & neck Hodgkin lymphoma PD-1 receptor 2017 DNA repair deficiency, MSI-high Bladder atezolizumab Hepatocellular 2018 CTLA-4 Cervical ipilimumab 2019 Breast Cancer (triple neg) “Leave me alone” “You don’t look like you’re from around here” Checkpoint inhibitors | Adverse effects 2018 TOP 5 ONC DRUGS What are the most common side effects? And what are the side effects that are unique to checkpoint 1. Lenalidomide inhibitors? 2. Nivolumab (+31%) $7.6 billion 3. Pembrolizumab (+88%) $7.2 billion When do these side effects typically develop? 4. Trastuzumab 5. Bevacizumab How do I manage immune-related adverse events? 7
6/20/2019 Checkpoint inhibitors | Adverse effects Checkpoint inhibitors | Adverse effects • Mr. S: 71M with metastatic melanoma. RASH: The most common adverse event • Dx: 9/2014 in setting evaluation for anemia and weight loss revealing lung and renal masses. When? Usually within the first few weeks. • Staging: Metastatic. Lung, renal, small bowel, brain, and spine lesions. Biopsy? Yes. Rule out TEN, DRESS, etc. • Treatment: Management: • 10/2014-2/2015: Ipilimumab -If less than 30% BSA ( grade 1 or 2 ), topical steroids • PR with progression of disease in brain and emollients. Oral antihistamines. • 3/2015-presentation: Pembrolizumab -If more than 30% BSA ( grade 3 ), discontinue immunotherapy. Consider oral systemic steroids. Maculopapular rash on back. -If grade 4 (SJS, TEN), discontinue immunotherapy. Admit. IV methylprednisolone 1-2 mg/kg. Checkpoint inhibitors | Adverse effects • Mr. T: 70M with metastatic lung cancer. Adverse events: General Adverse events: Immune • Dx: 4/2014 in setting of evaluation for anemia and weight loss. Skin (7%) Skin (10%) GI (6%) -rash • Staging: IIIA (4/2014); metastatic (7/2014). Musculoskeletal (3%) -pruritis Bilateral lungs, pleural with effusion. Endocrine (2%) -vitiligo • Treatment: Nervous system (2%) GI Respiratory (1%) Musculoskeletal (2%) • 4/2014: Chemoradiation Blood/lymphatic (1%) Endocrine (2%) • 10/2014: Carboplatin/pemetrexed followed by pemetrexed maint. • SD • 8/2015: paclitaxel/trastuzumab • SD • 9/2016: nivolumab Monitoring labs reveal a transaminitis (2.5 x ULN) 8
Recommend
More recommend
