Hematology and Oncology Flashcards

A 58-year-old man with newly diagnosed acute promyelocytic leukemia (APL) is started on ATRA and arsenic trioxide. On day 4, he develops fever, weight gain of 3 kg, and new bilateral pulmonary infiltrates. His WBC has risen from 2,000 to 18,000/µL. Which of the following is the most appropriate next step?

Answer: Add dexamethasone 10 mg IV twice daily and continue ATRA

This presentation is classic for differentiation syndrome (formerly ATRA syndrome), occurring in ~25% of APL patients treated with ATRA or arsenic trioxide. It is characterized by fever, weight gain, pulmonary infiltrates, and rising WBC. The correct management is to add high-dose dexamethasone (10 mg IV BID) while continuing ATRA — discontinuation is reserved only for severe cases with renal failure or respiratory failure requiring mechanical ventilation. Early steroid intervention is life-saving and ATRA should not be stopped empirically.

A 72-year-old woman with IgG kappa multiple myeloma achieves a complete response after lenalidomide, bortezomib, and dexamethasone (RVd). She undergoes autologous stem cell transplant (ASCT) and is now on lenalidomide maintenance. Surveillance serum protein electrophoresis at month 18 shows a new small M-spike of 0.2 g/dL. Serum free light chain ratio is normal. She is asymptomatic with stable skeletal survey. This finding is best classified as:

Answer: Biochemical relapse not meeting criteria for clinical relapse

Per IMWG (International Myeloma Working Group) criteria, biochemical relapse is defined by reappearance of serum or urine M-protein on two consecutive measurements without CRAB criteria (hyperCalcemia, Renal insufficiency, Anemia, Bone lesions) or other myeloma-defining events. A 0.2 g/dL M-spike with normal FLC ratio and no symptoms meets biochemical relapse, not clinical relapse requiring treatment change. Stringent CR requires absence of M-protein AND normal FLC ratio AND no clonal plasma cells by immunohistochemistry — clearly not met. MRD-negative requires sensitive assays showing no detectable disease.

A 45-year-old woman is found to have a JAK2 V617F-positive polycythemia vera. Her hematocrit is 52%, platelet count is 680,000/µL, and she has a prior history of splenic vein thrombosis. She is currently on phlebotomy and aspirin. Which of the following represents the most appropriate intensification of therapy?

Answer: Add hydroxyurea to achieve hematocrit <45%

This patient is high-risk PV (age >60 OR prior thrombosis — she has both, being 45 with splenic vein thrombosis making her high-risk by thrombosis criterion). High-risk PV patients require cytoreductive therapy; hydroxyurea is first-line. The ECLAP and CYTO-PV trials demonstrated that maintaining hematocrit <45% significantly reduces thrombotic events. Ruxolitinib (a JAK1/2 inhibitor) is second-line for patients intolerant of or resistant to hydroxyurea, not first-line. Anticoagulation alone does not address the underlying erythrocytosis driving thrombotic risk.

A 63-year-old man with chronic lymphocytic leukemia (CLL) and del(17p) by FISH receives venetoclax plus obinutuzumab. After completing 12 months of fixed-duration therapy, he achieves MRD-undetectable remission. Six months later, he presents with rapidly enlarging lymph nodes, a LDH of 4× ULN, and a biopsy showing large B-cell lymphoma. This transformation is most accurately described as:

Answer: Richter transformation to diffuse large B-cell lymphoma

Richter transformation (RT) refers to the development of an aggressive lymphoma — most commonly DLBCL (~95% of RT cases) — in a patient with pre-existing CLL/SLL. It occurs in 2–10% of CLL patients and portends a very poor prognosis (median survival ~5–8 months). Key features include rapid lymph node enlargement, markedly elevated LDH, B symptoms, and histologic confirmation of large cell transformation. BTK C481S mutation causes ibrutinib resistance, not venetoclax resistance. Tumor lysis syndrome occurs during treatment initiation, not months post-therapy.

A 55-year-old woman with metastatic non-small cell lung adenocarcinoma harboring an EGFR exon 20 insertion mutation has progressed on first-line platinum-based chemotherapy. Her oncologist considers targeted therapy. Which agent is specifically FDA-approved for EGFR exon 20 insertion mutations in NSCLC after platinum-based chemotherapy?

Answer: Amivantamab-vmjw

EGFR exon 20 insertions are distinct from the classic sensitizing mutations (exon 19 deletions, L858R) and confer primary resistance to first-, second-, and third-generation EGFR TKIs (erlotinib, afatinib, osimertinib). Amivantamab-vmjw, a bispecific EGFR-MET antibody, received FDA approval specifically for EGFR exon 20 insertion NSCLC after platinum-based chemotherapy based on the CHRYSALIS trial. Mobocertinib (now withdrawn) was another option but is no longer available. Osimertinib is approved for exon 19 del/L858R (first-line) and T790M (after first-gen TKI), not exon 20 insertions.

A 38-year-old man with relapsed/refractory classical Hodgkin lymphoma progresses after brentuximab vedotin and pembrolizumab. He undergoes salvage chemotherapy with GDP (gemcitabine, dexamethasone, cisplatin) and achieves a partial response. PET-CT shows Deauville score 4 in a single mediastinal node. He proceeds to autologous SCT with BEAM conditioning. Which of the following post-transplant strategies is most strongly supported by randomized evidence to improve PFS in this setting?

Answer: Maintenance brentuximab vedotin for up to 2 years

The AETHERA trial (NEJM 2015) was a landmark phase III RCT demonstrating that brentuximab vedotin (BV) maintenance for up to 2 years post-ASCT significantly improved PFS (42.9 vs 24.1 months, HR 0.57) in high-risk cHL patients, including those with primary refractory disease, relapse within 12 months, or extranodal disease. This led to FDA approval of BV in this post-ASCT maintenance setting. Pembrolizumab post-ASCT is under investigation but lacks mature phase III randomized evidence. Consolidative RT to a single Deauville 4 node is sometimes used but is not supported by the same level of RCT evidence as BV maintenance.