ALL or Nothing
According to NCCN guidelines, allogeneic transplant in first complete remission is recommended for adult ALL patients with this MRD threshold or higher after consolidation.
What is ≥0.01% (or MRD-positive status)?
NCCN recommends validated technology with a sensitivity of at least 10⁻⁴ (0.01%), with an FDA-approved NGS-based assay (sensitivity up to 10⁻⁶) as the preferred method.
This cytogenetic abnormality, found in ~30% of MDS cases, is the most common single chromosomal abnormality and is associated with a distinct clinical syndrome featuring macrocytic anemia, hypolobated megakaryocytes, and response to lenalidomide.
What is del(5q) / 5q minus syndrome?
Preferred therapy for MDS-5q per NCCN guidelines (category 1 when serum EPO >500 mU/mL).
MDS-003 (Ph. 2) and MDS-004 (Ph. 3)
MDS-004 trial (phase 3, n=205), RBC transfusion independence ≥26 weeks was 56.1% with lenalidomide 10 mg and 42.6% with 5 mg, vs 5.9% with placebo (both P < .001). Cytogenetic response rates were 50% (complete 29%) with 10 mg and 25% (complete 16%) with 5 mg.
Per NCCN guidelines, all patients with epithelial ovarian cancer should undergo germline and somatic testing for these two genes, regardless of family history.
What are BRCA1 and BRCA2?
Germline and somatic BRCA1/2 status informs maintenance therapy, particularly eligibility for PARP inhibitor maintenance. In the absence of a BRCA1/2 mutation, homologous recombination deficiency (HRD) status may provide additional info on the magnitude of benefit from PARP inhibitor therapy in advanced-stage disease.
Per NCCN guidelines, sentinel lymph node biopsy should be discussed and offered for melanomas with a Breslow thickness greater than or equal to this value.
What is 0.8-1.0 mm?
0.8 mm without ulceration (T1a): SLNB is not generally recommended
0.8 mm with ulceration, or 0.8–1.0 mm ± ulceration (T1b): SLNB should be discussed and considered.
>1.0 mm (T2a and higher, stage IB–II): SLNB should be discussed and offered.
Amivantamab is a bispecific antibody targeting both EGFR and MET. In the PAPILLON trial, it was combined with carboplatin/pemetrexed for first-line treatment of NSCLC with this specific EGFR alteration — historically one of the hardest to treat with standard TKIs.
What are EGFR exon 20 insertion mutations?
3rd most common type of EGFR mutation; up to 4–12% of all EGFR-mutated NSCLCs
Alters the conformation at the kinase-active site, rendering them largely insensitive to standard EGFR TKIs.
Median PFS: 11.4 months vs. 6.7 months (HR 0.40; 95% CI 0.30–0.53; P<0.001)
ORR: 73% vs. 47% (P<0.001)
18-month PFS: 31% vs. 3%
Interim OS (33% maturity) showed a favorable trend (HR 0.67; 95% CI 0.42–1.09)
This pediatric-inspired chemotherapy backbone, often named after a California-based children's hospital, revolutionized outcomes in adolescents and young adults with ALL.
What is CALGB 10403 (or 'AYA regimen')?
Children's Hospital of Los Angeles (CHLA)-affiliated Children's Oncology Group network
a preferred frontline induction and consolidation regimen for AYA patients without substantial comorbidities, for both Ph-negative B-ALL and T-ALL
EFS of 78.1 months. 3-year overall survival OS of 73%
This biallelic mutation pattern defines the most favorable-risk AML subgroup, with CR rates >90% and is often managed without allogeneic transplant in CR1.
What is biallelic CEBPA mutation aka CEBPAbi?
ELN 2022 update — bZIP in-frame mutations, not biallelic status, now define favorable risk: The ELN 2022 classification shifted the defining criterion from biallelic CEBPA mutations to *in-frame mutations affecting the bZIP (basic leucine zipper) region of CEBPA, irrespective of whether they are monoallelic or biallelic.
This monoclonal antibody, added to front-line carboplatin/paclitaxel and continued as maintenance, improved PFS in advanced ovarian cancer in the GOG-0218 and ICON7 trials.
What is bevacizumab?
GOG-0218 (N=1,873); stage III–IV disease --> bevacizumab-throughout arm showed a median PFS of 14.1 months vs. 10.3 months with chemo alone (HR 0.72; 95% CI 0.63–0.82; P<0.001).
Similar interventions but very different trial designs. Neither demonstrated OS benefit except in a small high-risk subgroup in ICON7 (stage IV, inoperable stage III, or >1 cm residual disease).
This first-in-class anti-PD-1 therapy was approved in 2018 for locally advanced or metastatic cutaneous squamous cell carcinoma based on the EMPOWER-CSCC-1 trial.
What is cemiplimab (Libtayo)?
LA: ORR of 44-50%, including 13-17% CR and 31-33% PR
Met: ORR of 47-49%, with durable responses
(Both) At 42.5 months median follow-up (final analysis): The estimated 12-month DOR was 88.3%, and median PFS was 26.0 months.
The PACIFIC trial established durvalumab as maintenance therapy after concurrent chemoradiation in unresectable stage III NSCLC — but patients had to start durvalumab within this time window after completing radiation.
What is 42 days (1-42 days post-CRT)?
The original protocol required initiation within 1–14 days, but this was expanded to 1–42 days via a protocol amendment on February 18, 2015, after the trial had already begun.
An unplanned subgroup analysis from PACIFIC suggested that patients who started durva within 14 days of completing radiation had superior PFS and OS compared to those starting between 14–42 days.
Subsequent real-world analyses suggest that timing of durva initiation within a broad window (up to 56d on average) does not meaningfully affect outcomes, and the PACIFIC ≤14-day subgroup finding should not drive clinical decision-making.
This CD22-directed antibody-drug conjugate improved survival in relapsed/refractory B-ALL but carries a black box warning for this potentially fatal hepatic complication.
What is sinusoidal obstruction syndrome (SOS) / veno-occlusive disease (VOD)? Risk is greatest in patients who subsequently undergo HSCT
Besponsa (inotuzumab ozogamicin)
Phase 3 INO-VATE trial (NEJM, 2016) - 14% VOD
Cat 1 preferred regimen for R/R Ph-negative B-ALL
Also has BBW for increased post-HSCT non-relapse mortality
This hereditary myeloid malignancy predisposition gene, characterized by germline mutations that may present in adults >50 years, is the most common inherited cause of familial MDS/AML and requires confirmatory testing on non-hematopoietic tissue.
What is DDX41?
Unlike most hereditary cancer predisposition syndromes, DDX41-associated myeloid malignancies typically present at older ages (median ~66–69 years), overlapping with the age distribution of sporadic MDS/AML. Risk is negligible before age 40.
Without pre-existing cytopenias, dysplasia, or organ dysfunction prior to malignancy, though patients may have macrocytosis and/or mild cytopenias beforehand.
DDX41-mutated MDS/AML is characterized by hypocellularity, low blast percentage, normal karyotype, and relatively favorable outcomes.
This rare but aggressive uterine malignancy, comprising ~3-5% of uterine cancers, has a disproportionately high mortality rate, is classified as p53-abnormal/copy number high, and historically has had limited treatment options until recent immunotherapy advances.
What is uterine serous carcinoma (or uterine carcinosarcoma would also be accepted)?
Responsible for a disproportionate 40–80% of endometrial cancer-related deaths.
Frequent cell cycle deregulation involving CCNE1 amplification (45%), MYC, PPP2R1A, PIK3CA, ERBB2 (HER2), and CDKN2A. Typically mismatch repair proficient (pMMR)
NRG-GY018: Carboplatin/paclitaxel + pembro
RUBY: Carboplatin/paclitaxel + dostarlimab
DUO-E: Carboplatin/paclitaxel + durvalumab ± olaparib maintenance
This Hedgehog pathway inhibitor was the first FDA-approved targeted therapy for locally advanced or metastatic BCC, though its use is limited by side effects including muscle spasms, dysgeusia, and alopecia.
What is vismodegib (Erivedge)?
FDA approval January 2012 based on phase 2 ERIVANCE BCC trial, which demonstrated ORR of 43% in locally advanced BCC and 30% in metastatic BCC
Aberrant activation of Hedgehog signaling pathway — most commonly through loss-of-function mutations in PTCH1 (~80–90% of BCCs) or activating mutations in SMO (~10%) — drives BCC pathogenesis.
Tarlatamab, the first bispecific T-cell engager approved in solid tumors, targets CD3 on T cells and this surface protein — an inhibitory Notch ligand aberrantly expressed on 85-96% of SCLC cells but minimally expressed in normal adult tissues.
What is DLL3 (delta-like ligand 3)?
Normally localized intracellularly in healthy adult tissues. Aberrantly expressed on the cell surface of SCLC cells, making it a highly attractive therapeutic target with a favorable on-tumor/off-tumor expression profile.
DeLLphi-301 (Ph.2) and DeLLphi-304 (Ph.3)
Median OS was 13.6m vs 8.3m
Median PFS was 4.2 months vs 3.7 months
ORR: 35% with tarlatamab vs 20% with chemo
This CD19-directed CAR-T product, approved for B-ALL up to age 25, showed an 81% remission rate in the ELIANA trial.
What is tisagenlecleucel (Kymriah)?
First FDA-approved CAR T-cell therapy (August 2017), indicated for patients up to 25 years of age with R/R CD19+ B-ALL.
12-month EFS: 50%
12-month OS: 76%
At the 3-year update (median follow-up 38.8 months), the overall remission rate was 82%, with 3-year OS of 63% and 3-year EFS of 44%
Luspatercept was approved for lower-risk MDS with ring sideroblasts based on this phase III trial that showed superiority over erythropoiesis-stimulating agents for transfusion independence.
What is the COMMANDS trial?
Primary endpoint was RBC transfusion independence (TI) ≥12 weeks with concurrent mean Hb increase ≥1.5 g/dL during weeks 1–24. In the primary analysis, 60% of luspatercept-treated vs. 35% of epoetin alfa-treated patients met this endpoint (p<0.0001). Benefit was most pronounced in SF3B1-mutated patients.
Preceded by the MEDALIST trial, which first established luspatercept's efficacy in lower-risk MDS with ring sideroblasts
This antibody-drug conjugate targeting folate receptor alpha was approved for platinum-resistant ovarian cancer based on the SORAYA and MIRASOL trials, but requires confirmation of target expression by immunohistochemistry before use.
What is mirvetuximab soravtansine (Elahere)?
SORAYA (Ph. 2) and MIRASOL (Ph. 3)
Approved by the FDA for FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who have received 1-3 prior systemic treatment regimens.
3 components: an FRα-binding antibody, a cleavable disulfide linker, and the maytansinoid DM4, a potent tubulin-targeting cytotoxic payload.
VENTANA FOLR1 (FOLR1-2.1) RxDx Assay
PS2+ scoring method: ≥75% of viable tumor cells with moderate (2+) or strong (3+) membrane staining intensity --> ~30–35% of platinum-resistant ovarian cancers
In melanoma staging, the presence of microsatellites, satellites, or in-transit metastases — all representing intralymphatic spread — automatically classifies a patient as at least this N-category.
What is N1c (or stage III)?
Microsatellitosis defines at least N1c and at least pathologic stage IIIB disease. If a sentinel lymph node biopsy is subsequently positive, the patient is upstaged to at least N2c, stage IIIC.
Doesn't change tx - they all get neoadj IO - unless unresectable.
Zenocutuzumab targets HER2/HER3 signaling and was approved for NSCLC harboring this ultra-rare gene fusion — found in <1% of cases — that drives ligand-independent HER3 activation.
What are NRG1 fusions?
Enriched in invasive mucinous adenocarcinoma histology and in never-smokers.
RNA-NGS as DNA-based panels may miss these fusions due to large intronic regions. (CARIS includes this; many don't.)
Producing chimeric proteins that constitutively bind HER3, triggering HER2-HER3 heterodimerization and downstream PI3K/AKT/mTOR and MAPK signaling independent of the normal neuregulin-1 ligand
eNRGy trial (Ph. 2)
Bispecific antibody that simultaneously binds HER2 (domain 4) and HER3 (domain 1), physically blocking the NRG1 fusion protein from engaging HER3 and thereby preventing HER2-HER3 heterodimerization and downstream oncogenic signaling.
Name two different specific alterations in B-ALL that would be classified as Ph-like B-ALL and may warrant additional treatment such as TKIs.
CRLF2 rearrangements (IGH-CRLF2, P2RY8-CRLF2): ~50–75% of cases; frequently co-occur with JAK1/2 mutations
ABL-class fusions (ABL1, ABL2, CSF1R, PDGFRA, PDGFRB): ~10–15% of cases
JAK2/EPOR rearrangements: ~5–12%
Other kinase alterations: NTRK3, FLT3, FGFR1, LYN, PTK2B, TYK2, and RAS pathway mutations (~2–8%)
This mutation, enriched in therapy-related MDS and often co-occurring with TP53, involves a gene encoding a phosphatase that negatively regulates p53 and is associated with prior cytotoxic therapy exposure.
What is PPM1D?
(Protein Phosphatase, Mg²⁺/Mn²⁺-Dependent 1D), also known as WIP1 (Wild-type p53-Induced Phosphatase 1). Frequent TP53 co-mutation.
Nearly always truncating (nonsense or frameshift) and localized to exon 6, the terminal exon of the gene --> a gain-of-function effect that augments dephosphorylation of key DDR targets including TP53, CHEK2, ATM, MDM2, and MDM4.
Per the NCCN MDS Guidelines, PPM1D has an overall incidence of ~5% in MDS and is "associated with therapy-related MDS, but not associated with adverse prognosis independent of TP53".
This oral progestin is the preferred first-line systemic therapy for grade 1 endometrioid endometrial cancer that is confined to the uterus in patients who desire fertility preservation and/or are not surgical candidates.
What is levonorgestrel-releasing IUD?
While megestrol acetate and medroxyprogesterone acetate (MPA) are both used as oral progestins in this setting, the NCCN guidelines actually designate the levonorgestrel-releasing IUD as the overall preferred progestin-based therapy, with oral progestins (megestrol and MPA) listed as "other recommended" options.
This oncolytic viral therapy, injected intralesionally, was the first FDA-approved oncolytic virus for unresectable stage IIIB-IV melanoma, though its use has declined with the rise of checkpoint inhibitors.
What is talimogene laherparepvec (T-VEC / Imlygic)?
Genetically modified HSV-1 oncolytic immunotherapy that was FDA-approved in October 2015 — the first and, to date, only oncolytic virus approved in the US for cancer treatment.
OPTiM Trial (Phase III)
Has not been shown to improve OS or have an effect on visceral metastases.
MASTERKEY-265 trial demonstrated that adding T-VEC to pembro did not offer statistically significant additional clinical benefit.
Telisotuzumab vedotin is an ADC targeting c-Met protein that was approved for previously treated non-squamous NSCLC — but only in tumors meeting this specific IHC threshold, making companion diagnostic testing mandatory.
What is c-Met IHC 3+ in ≥50% of tumor cells (high c-Met overexpression)?
VENTANA MET (SP44) RxDx Assay
NGS, RT-PCR, and FISH are not valid methods for detecting c-Met protein overexpression.
LUMINOSITY trial
ORR was 35% with a median DOR of 7.2 months
Do not confuse!! with MET exon 14 skipping (genomic alteration) → determines eligibility for capmatinib, tepotinib, or crizotinib
In 1990, E. Donnall Thomas won the Nobel Prize in Physiology or Medicine for developing this procedure — which he first performed in 1957 between identical twins — and was told by colleagues for decades that the idea was 'gruesome' and would never work.
What is bone marrow transplantation?
First performed this procedure around 1957 between identical twins, and in 1959 he reported that a patient with end-stage leukemia treated with TBI followed by infusion of her identical twin's marrow achieved a three-month remission.
Early 1960s: Identification and typing of HLA (the major histocompatibility complex) made allogeneic transplantation feasible
Late 1960s: First successful long-term survivors from HLA-matched sibling transplants
1970s: Thomas and colleagues cured patients with end-stage leukemia using marrow from HLA-identical siblings after total-body irradiation combined with cyclophosphamide; transplantation during first remission achieved >50% cure rates