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Oncology Exam 4
Frei Chronic Leukemia C
| Question | Answer |
|---|---|
| Leukemia can come in 4 forms: | Acute Lymphocytic Leukemia (ALL) Acute Myelogenous Leukemia (AML) Chronic Lymphocytic Leukemia (CLL) Chronic Myelogenous Leukemia (CML) |
| What is Leukemia? | -Malignant proliferation of a WBC involving the bone marrow -Lymphoma: A mass lesion in the mediastinum or elsewhere AND < 25% blasts in the bone marrow -Leukemia > 25 % blasts in the bone marrow ± a mass lesion |
| Acute Vs Chronic: Acute Onset? Cell type? Survival? Tx? | Rapid, Immature blast cells, May be fatal, Chemotherapy +/- HSCT |
| Acute Vs Chronic: Chronic Onset? Cell type? Survival? Tx? | Gradual, Mature cell, Longer survival, May be resistant |
| Estimated New cases of Leukemia, Lymphoma and Myeloma? | Myelomas (15%) (least common) Leukemias (32%) -Lymphomas (53%) |
| 5-year relative survival rates by year of diagnosis: | changes in 5-year survival rates over the years. Light grey, red, and dark grey is the survival rates ranging over a time frame of 1960 to 2008. This is how our survival rates have changed over the last 50 years *5-year survival rates have increased over the last 50 years for all the different kinds of leukemia cancers |
| Incidence and survival comparison? Which has the highest incidnce? highest mortality? | CLL (highest incidence and most common) AML (highest mortality) |
| Chronic Lymphocytic Leukemia): General info? | -Highest Incidence of all leukemias -High prevalence due to slow progression -Average age of diagnosis is 70 years old, But can happen as young as 30 -Types of CLL: B-cell - most common (95%), T-cell - less common, but progresses more rapidly |
| Risk factors of CLL (Chronic Lymphocytic Leukemia) include? | family history, Age, Sex, Exposure to agent orange, Monoclonal B-cell lymphocytosis |
| Diagosis of CLL is established by ___ ____ of blood | Established by flow cytometry of blood -Presence of monoclonal B lymphocytes ≥5 x 109/L in peripheral blood based on flow cytometry -Clonality of B cells should be confirmed by flow cytometry -Adequate immunophenotyping to establish diagnosis by flow cytometry: kappa/lambda, CD19, CD20, CD5, CD23, CD10, CD200 -if flow cytometry is used to establish diagnosis, also include cytospin for cyclin D1 or fluorescence in situ hybridization (FISH) for t(11;14); t(11q;v) to exclude mantle cell lymphoma (MCL) |
| Symptoms of CLL include? | Fatigue, Fever, swollen lymph nodes, Night sweats, unexplained weight loss, Pain or sense of fullness under ribs |
| Complications of CLL include? | Can develop into lymphoma; increased risk of skin, lung, and colon cancer, anemia, thrombocytopenia, frequent infections |
| Goals in CLL? | -relief of symptoms; correct cytopenias; response |
| Workup case for CLL? | -History & Physical (measurement of liver, spleen, and palpable lymph nodes) -Peripheral Blood Smear -Performance Status -Assess B symptoms (occurs in CLL): Fever (>100.4F), Drenching night sweats, Weight loss (>10% in 6 months) -Perform Flow Cytometry |
| CLL evaluation: TEST BEFORE TREAT: | Test FISH and TP53 mutation before every tx -Test IgVH mutation status before the1st tx -deletion 17p or del(17p)= no chemotherapy -TP53 mutation = No Chemotherapy -IgVH unmutated = NO FCR -IgVH mutated = possible FCR *assess FISH for Del(17p); TP53 mutation status; CPG-stimuated karotype; IGHV mutation status; imaging as appropriate; bone marrow aspirate and biopsy |
| CLL Cytogenetics Analysis: Frei noted that Deletion 11q and Del 17p/TP53 mutatation, why? | Deletion 11 q – may respond well to fludarabine + alkylator ⭐️ Del 17 p/TP53 – poor response to chemoimmunotherapy (asociated with very low survivial |
| Treatments for CLL throughout the years: 2010 change? | BTK inhibitors (Ibrutinib, Acalabrutinib, Zanubrutinib) PI3K inhibitors (Idelalisib, Duvelisib) BCL-2 inhibitors (Venetoclax) Novel CD20 mAb (Obinutuzumab) *where we got our new 1st line tx |
| CLL treatments options include? | Watchful waiting; radiation therapy; chemotherapy; Surgery; Targeted therapy; Transplant (if refractory) |
| CLL – When to Treat: Treatment should begin when... | -Fevers for more than 2 weeks without evidence of infection, extreme fatigue, night sweats, unintentional weight loss (B-symptoms) -Increasing anemia or thrombocytopenia due to bone marrow failure -Bulky or progressive lymphadenopathy or splenomegaly (spleen > 6 cm below costal margin, lymph nodes > 10 cm) -Autoimmune cytopenias not responsive to corticosteroids -Threatened end-organ function -Patient preference |
| Consider the fitness of the pt when it comes to selecting tx: | Cleared for treatment – younger or physiologically fit patients Maybe – older patient who cannot tolerate aggressive therapy No treatment – patient with significant co-morbidities |
| CLL 1st line treatments include what preferred regimens? | Venetoclax + Obinutuzumab Venetoclax + acalabrutinib +/- obinutuzumab Zanubrutinib Acalabrutinib +/- Obinutuzumab |
| ADRs of CLL regimens: Acalabrutinib: DI include? | Avoid CYP3A4 strong inh or inducers Avoid antacids and H2 blockers; avoid grapefruit *remember its given BID PO *Toxicities with Afib and Headache *more issues with Afib and Headache |
| ADRs of CLL regimens: Zanubrutinib: DI include? | Avoid CYP3A4 strong inh or inducers; avoid grapefruit *given BID or daily PO *Toxicities with Infection *infection risk higher with Zanubrutinib |
| ADRs of CLL regimens: Obinutuzumab: DI? CI? Toxicities? | -No DI; Dosing is IV⭐️; -CI: ⭐️Hep B reactivation leading to liver failure; PML; Infusion rxn⭐️; -TLS Prophylaxis: for high-risk pts $; Toxicities include: Neutropenia; Hyperuricemia *PML – progressive multifocal leukoencephalopathy. $ - Patients with high tumor burden, high circulating absolute lymphocyte counts (greater than 25 x 109/L) or renal impairment are considered at risk of tumor lysis syndrome and should receive prophylaxis. |
| ADRs of CLL regimens: Venetoclax: DI? CI? Toxicities? | DI: Avoid CYP3A4 strong or mod inducers; adjust dose if taking strong or mod CYP3A inhibitors or Pgp inhibitors Dosing: Daily, PO⭐️ ⭐️CI: Use of CYP3A inhibitors at initiation and during ramp up phase TLS prophylaxis: Allopurinol and Hydration ⭐️ Toxicities include: Neutropenia and Hyperuricemia |
| Supportive care for CLL includes? | Vaccination, Infection prophylaxis, and Tumor Lysis Syndrome Prophylaxis |
| Supportive care for CLL (Vaccines), which ones? | -Yearly influenza -Pneumococcal conjugate vaccine (PCV20) to newly diagnosed patients who are pneumococcal vaccine naïve then give PPSV23 at least 8 weeks later -Zoster vaccine recombinant, adjuvanted -No live vaccines |
| Supportive care for CLL (Infection prophylaxis), considerations? | -Patients on BTK small molecule inhibitors consider PJP and varicella zoster virus (VZV) prophylaxis -Venetoclax consider fluoroquinolone prophylaxis during neutropenia; consider fungal prophylaxis during neutropenia. -Monitor for fungal infection. |
| Supportive care for CLL (Tumor Lysis Syndrome Prophylaxis), considerations? | Some CLL pts receiving venetoclax or obinutuzumab receive 1) hydration and/or 2) allopurinol or febuxostat |
| Chronic Myelogenous Leukemia (CML) | Most common myeloproliferative disease 1.5 cases per 100,000 population per year More common in men Not familial (identical twin studies) Radiation exposure may contribute to disease development Philadelphia chromosome in healthy population |
| Epidemiology/Etiology of CML | About 15% of all new cases of leukemia are chronic myeloid leukemia. About 1 person in 526 will get CML in their lifetime in the United States. The average age at diagnosis of CML is around 64 years. Mainly affects adults, and is rarely seen in children. |
| Chronic Myelogenous Leukemia (CML) Change in paradigm? | -Movement towards targeted therapy -Establish specific tumor markers -Exploit differences in tumor cells -Maintain efficacy and limit toxicity *not using chemo in CML anymore--> more so targeted agents |
| Chronic Myelogenous Leukemia (CML) diagnosis? | Immature myeloid cells experience a genetic abnormality, known as BCR-ABL, which causes uncontrolled numbers of granulocytes. These granulocytes don’t function normally. So, can see Inc WBC but dec immunity |
| CML (Philadelphia Chromosome) is a? | -Genetic abnormality first described in 1960 -Specific abnormality describe in 1973: translocation of Abl and Bcr genetic information; t(9;22)(q34;q11) -Leads to production of Bcr-Abl protein -Constitutively activated tyrosine kinase -Creates the perfect model for targeted therapy: Nearly uniformly present (95%); Sole abnormality in early stage disease |
| CML Clinical Presentation? | -Leukocytosis -Thrombocytosis (-penia) -Anemia -Basophilia + Eosinophilia -Splenomegaly: Abdominal pain, nausea, Early Satiety -No increased infection risk |
| Natural History for Chronic CML: Survival? | Most pts stay in the chronic phase. 3 – 5 years (prior to TKIs); Imatinib - at 10 Years have 83% survival *increased outcome |
| Definition of Response of CML: | Response: Hematologic (complete CBC, WNL, Non-palpable, spleen. Cytogenic and philadelphia cells: Complete (0), Major (1-35), minor (36-65), Min. (66-95), None (95). Molecular: Complete (non-detectable BCR-ABL transcripts), Major (<0.1% BCR-ABL When you start tx with CML, your going see that the hematologic abnormalities normalized. that means if yiou drew a CBC, yiou would see that their WBC count, anemia, platelets would normalize out--> 1st level of response. |
| Sokal Risk Score: What are factors associated with risk calculation? risk category? | Pt age, spleen size, platelet count, % blast in peripheral blood; *Higher the score, the harder to get the response we're looking for. So a Sokal score that is low would be a good thing (meaning the pt will have a better cytogenic response) Low <0.8; Intermediate: 0.8-1.2; High: >1.2 *Sokal correlates with likelihood of achieving a complete cytogenetic response (cCyr) |
| CML (Chronic Myelogenous Leukemia): Chronic Phase CML--> Low Risk Sokal Score (<0.8), Tx options? | Imatinib1 Dasatinib2 Nilotinib2 Bosutinib2 Asciminib3 |
| CML (Chronic Myelogenous Leukemia): Chronic Phase CML--> Intermediate (0.8-1.2) or High Risk Sokal Score (>1.2)?, Tx options? | Bosutinib2 Asciminib3 Nilotinib2 Dasatinib2 |
| CML (Chronic Myelogenous Leukemia): Chronic Phase CML--> T315I mutation, Tx options? | Ponatinib3 (preferred) Asciminib3 *mutation will override the sokal score so if you see the mutation, choose the agent that would treat the mutation. |
| IRIS (imatinib) | This is the trial that got Imatinib approved. sig. better in survival data compared to other regimens being used |
| Clinical Outcomes of TKIs for 1st line therapy in CML-CP | Takeaway--> Of the 2nd and 3rd generation TKIs have been showing better rates of response compared to what was standard of care, which is Imatinib, so the 2nd and 3rd generation showed better response rates than 1st generation Imatinib |
| Selection of TKIs for 1st line therapy in CML-CP | Focus on where you can't use these drugs--> Nilotinib--> problems with CV, HTN, PAD. -Imatinib is not a good choice for pts with renal disease or GI disease -Dastanib is not a good choice for pts with pleural effusion and/or pulmonary disease (including PAH) -Bosutinib is not a good choice for liver disease, renal disease, or GI disease |
| Asciminib (Scemblix): MOA? FDA indication? | BCR-ABL tyrosine kinase inhibitor, especially targets CML cell with T315I mutation FDA Indications: Chronic myeloid leukemia (CML) With T315I-positive mutation Dose 200 mg po BID Chronic myeloid leukemia (CML) After progression on 2 different TKI Dose 80 mg po daily |
| TKIs include which drugs? | Imatinib (1st gen, NAUSEA) Dasatinib (2nd gen, Fluid retention (pleural/pericardial effusions), Nilotinib (2nd gen, QTc prolongation and metabolic syndrome), Bosutinib (2nd gen, BID, Diarrhea), Ponatinib (3rd gen, vascular occlusion/thromboembolism, Hepatotoxicity) Asciminib (3rd gen, BID, pancreatic toxicity) |
| Imatinib has improved tolerability when taken with ___ | food |
| Which TKI's can be taken w/ or w/o food? | Dasatinib; Ponatinib |
| Which TKIs should we take on an empty stomach? | Nilotinib |
| Which TKI needs to be taken without food? | Asciminib |
| Which TKI should be taken with food? | Imatinib (to improve tolerability), and Bosutinib |
| Stopping TKI therapy: Discontinuation of TKIs appears safe in certain CML patients that meet ALL of the following criteria: | -Adult -Chronic phase CML (most common, at least 90% of pts) -TKI therapy for at least 3 years -Measure BCR-ABL transcript levels -Stable molecular response for 2 years or more -Monthly molecular monitoring for first 6 months, then bimonthly during months 7 – 12, and quarterly thereafter *If loose MMR, must restart TKI within 4 wks |
| Approximately ___ to ____ of pts who d/c TKI therapy after achieving DMR experience recurrence w/in 12 months of tx cessation, in some cases as early as 1 month after d/c of TKI therapy | 40-60%⭐️ |
| Summary of CML Tx: First line therapy? | -Imatinib -Dasatinib -Nilotinib -Bosutinib (chronic phase only); Know agents for mutations; Comparison is limited by short follow-up; long term follow-up is needed; *know DI: PPI drug interaction |
| Which TKI’s have warnings to avoid PPI’s? | Dasatanib, Nilotinib, Bosutinib |
| Which of the following is first line treatment of CLL? | Zanubrutinib |
| Which of the following cancers happens most often in children vs adults? | ALL |
Created by:
Xander635
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