Mutations Galore
3 mutations associated with favorable risk AML?
Favorable: remember multiples of 8 (8;21 CBF, inv 16, CEBPAx2, NPM1, RUNX1 with RUNX, IDH2, APL 15:17)
Target of Gemtuzamab?
Gemtuzamab: CD33 (High yield: increases risk for sinusoidal obstruction syndrome)
Patient comes in with WBC 150k and lots of blasts on peripheral smear. On questioning they are altered, SOB and report blurry vision. You suspect leukostasis. What are 3 potential treatment options to consider?
Leukapheresis
Hydrea
AraC
Induction chemo
Flow pattern: CD33+, CD34-, HLA-, DR-
What is the suspected diagnosis?
APML - promyelocytes differentiated one step above blasts
AML would be CD34+ CD33+
First line treatment for metastatic HER2+ breast cancer ?
Phase III CLEOPATRA trial (Clinical Evaluation of Pertuzumab and Trastuzumab)
Looked at docetaxel (i.e. taxotere), herceptin (i.e. trastuzumab) and pertuzumab (THP) vs. TH + placebo
Combined treatment with pertuzumab, trastuzumab, and taxane is standard of care first-line therapy for HER2+ metastatic disease
3 mutations to check for possible treatment options in 2nd line HR + metastatic breast cancer?
ESR1 mutation (Elacestrant)
PIK3CA mutation (Alpelisib + Fulvestrant)
gBRCA mutation (PARPi)
HER2 low would be after chemo
Name 3 FLT3 inhibitors?
FLT3 inhibitors are divided into first generation multi-kinase inhibitors (such as sorafenib, lestaurtinib, midostaurin) and next generation inhibitors (such as quizartinib, crenolanib, gilteritinib)
What lab value indicates high risk APML?
WBC >10
Can consider adding Gemtuzumab Ozogamicin (GO, Mylotarg)
Also consider prophylaxis for differentiation syndrome with steroids.
Keep in mind the highest mortality with APML is at diagnosis and induction - biggest concern is intracranial hemorrhage.
AML mutation associated with abnormal eosinophilia on peripheral smear?
inv(16) = t(16;16) = CBF-MYH11 AML (good risk)
3 indications for sending germline BRCA testing (which patients)?
NCCN guidelines recommend testing any female with a personal history of breast cancer under age 45 or a personal history of breast cancer diagnosed before age 50 and a second primary breast cancer, one or more relatives with breast cancer, or an unknown or limited family medical history
A personal history of triple negative breast cancer diagnosed at age 60 or younger.
A personal history of two or more types of cancer
A personal history of ovarian cancer
A personal history of male breast cancer
A personal history of breast cancer and one or more relatives with breast cancer diagnosed before age 50, two or more relatives diagnosed with breast cancer at any age, one or more relatives with ovarian cancer, one or more relatives with male breast cancer, or two or more relatives with prostate cancer or pancreatic cancer
A personal history of breast cancer and Ashkenazi (Eastern European) Jewish ancestry
A personal history of prostate cancer or pancreatic cancer with two or more relatives with BRCA-associated cancers
A history of breast cancer at a young age in two or more blood relatives, such as your parents, siblings or children
A relative with a known BRCA1 or BRCA2 mutation
One or more relatives with a history of cancer that would meet any of these criteria for gene testing
HIGH YIELD: ENSURE THIS IS BRCA GERMLINE TESTING NOT SOMATIC TESTING
Most likely mutation associated with Alkylating agents in t-AML
-5/-7/TP53 = alkylating agents
TP53 (located on 17p13.1)
Alkylating agents (Platinum, Cyclophosphamide) with MDS and abnormality in chromosome 5 or 7 (present 5-7 years after chemo)
What are main differences in the side effect profiles of Letrozole (Aromatase Inhibitors) vs SERMs?
Menopausal symptoms are the same!
DVT and uterine cancer are not a concern with AI
With AI, bone loss in postmenopausal is a concern and should be monitored with baseline DEXA scan and every 2 years afterwards. With Tamoxifen, bone loss in premenopausal. Has protective effect on postmenopausal.
AI class also causes arthralgias and myalgias: occur in 50% of patients.
Newly diagnosed AML started on 7+3. Day 8 of treatment pt develops bilateral ear pain, swelling and redness. What's the diagnosis and associated drug?
Cytarabine ears (toxic erythema of chemotherapy)
Cytarabine can also cause neurotoxicity
At least 2mm margins for lumpectomy are considered negative and reduce ipsilateral recurrence. Lumpectomy is usually followed by XRT.
3 indications for allo transplant in AML?
Intermediate to Poor risk in CR after cycle 1
Anybody in CR2
Primary refractory AML
Most likely mutation associated with Topoisomerase II inhibitors and alkylating agents in t-AML
11q23.2 = KMT2A = Topo II
Topo II inhibitors (Anthracylines or Etoposide) no MDS and abnormality in chromosome 11q23 MLL KMT2A (usually 1-3 yrs after chemo);
Substrate that leads to anaphylactoid reactions for
1) Docetaxel
2) Paclitaxel
polysorbate 80 = docetaxel
Cremophor = Paclitaxel
What are the 3 main mechanisms of hypercalcemia of malignancy
Humoral hypercalcemia (PTHrP leads to downstream increase in osteoblasts)
Local osteolytic (local cytokines secreted by tumors and activates osteoblasts)
1,25 Vit D secreting lymphomas
AML mutation associated with cup shaped myeloblasts on peripheral smear?
NPM1 mutated AML
4 Minimum criteria for a diagnosis of inflammatory breast cancer (Based on International panel of experts published guidelines)
A rapid onset of erythema (redness), edema (swelling), and a peau d'orange appearance (ridged or pitted skin) and/or abnormal breast warmth, with or without a lump that can be felt.
The above-mentioned symptoms have been present for less than 6 months.
The erythema covers at least a third of the breast.
Initial biopsy samples from the affected breast show invasive carcinoma.
Mutation that portends resistance to AI therapy in breast cancer and what drug could you switch to?
ESR1 mutations - found in ~15-20% of metastatic patients
selective estrogen receptor degrader (SERD); These drugs ends in “-strant” including oral elacestrant or IM fulvestrant
What is the Antibody-drug targets for Sacituzumab govitecan?
ADC to trop-2 which is universal expressed on breast cancer cells
Trop-2-directed antibody and topoisomerase inhibitor drug conjugate
What are the laboratory changes that define TLS and what defines clinical TLS?
Lab TLS: ≥2 changes in a 24 hour period ≤3 days prior or 7 days after cytotoxic therapy hyperuricemia (≥8), hyperphosphatemia (≥4.5), hyperK (≥6), or hypoCa (≤7)
Clinical TLS: Lab TLS + 1 of the following: SCr >1.5x ULN, seizure, arrhythmia, sudden death
What special consideration does the rare t(11:17) mutated APML have that normal 15;17 APML does not?
resistance to ATRA
Name the syndrome
Inherited pancreas problems (ie exocrine pancreatic insufficiency)
Growth retardation/skeletal defects
Cytopenias (neutropenia)
MDS/AML with iso7q
Shwachman-Diamond Syndrome