Study aid only. Verify against current guidelines before clinical use.

Hematologic malignancies: high-yield review

Malignant Hematology
Malignant heme Q

Acute leukemias: high-yield

  • AML:
    • Cytogenetic risk (ELN 2022): favorable (t(8;21), inv(16), NPM1 mut without FLT3-ITD (adverse-risk cytogenetics override NPM1 to adverse), in-frame bZIP CEBPA mut), intermediate (NPM1 mut with FLT3-ITD, FLT3-ITD without NPM1, t(9;11), other unclassified abnormalities including normal karyotype without a defining mutation), adverse (complex, monosomal, TP53, MECOM, etc.). APL t(15;17) is classified separately, outside the ELN scheme.
    • 7+3 induction: cytarabine + daunorubicin/idarubicin.
    • CPX-351 (Vyxeos): for therapy-related AML or AML-MRC. Improved OS in older.
    • Targeted: FLT3 (midostaurin, gilteritinib, quizartinib), IDH1 (ivosidenib, olutasidenib), IDH2 (enasidenib), CD33 (gemtuzumab), Hedgehog (glasdegib), BCL2 (venetoclax), menin (revumenib for R/R KMT2A-r or NPM1-mut; ziftomenib for R/R NPM1-mut).
    • Older / unfit: ven + aza (VIALE-A: mOS 14.7 vs 9.6 mo).
    • APL (acute promyelocytic leukemia): t(15;17) PML-RARA. ATRA + arsenic trioxide for low/int risk; add idarubicin for high (WBC >10K). Watch for differentiation syndrome (dex prophylaxis).
  • ALL:
    • B-ALL: Ph+ → TKI (imatinib, dasatinib, ponatinib) + chemo. Blinatumomab for MRD+ or relapsed. CD22 (inotuzumab). CD19 CAR-T (tisa, brexu).
    • T-ALL/LBL: asparaginase-containing regimens; nelarabine for refractory.
    • Ph-like ALL: CRLF2/JAK2/ABL1 alterations; TKI candidate.
    • Obe-cel (Aucatzyl, FELIX NEJM 2024, FDA Nov 2024): fast-off CD19 CAR-T for R/R adult B-ALL; less CRS/ICANS; first CAR-T approved without REMS.
    • Blina 1L (E1910 NEJM 2024, FDA Jun 2024): adding 4 cycles blinatumomab to consolidation in MRD-neg Ph- B-ALL adults: 3-yr OS 85% vs 68% (HR 0.41). Standard for newly dx CD19+ Ph- B-ALL in CR.
    • Ponatinib 1L Ph+ ALL (PhALLCON, FDA Mar 2024): ponatinib + chemo: MRD-neg CR 30% vs 12% imatinib; preferred TKI in fit newly dx Ph+ ALL.

CML

  • BCR-ABL t(9;22). Chronic, accelerated, blast phase (ICC 2022 retains accelerated phase; WHO 5th edition uses a biphasic model of chronic and blast phase).
  • 1L TKI: imatinib, dasatinib, nilotinib, bosutinib, asciminib (STAMP inhibitor, ABL myristoyl pocket; 1L per ASC4FIRST, FDA Oct 2024).
  • Resistance / T315I: ponatinib, asciminib.
  • Treatment-free remission (TFR) after sustained DMR (MR4 or deeper) for ≥2 yrs (on TKI ≥3 yrs).

CLL / SLL

  • Diagnosis: ≥5 × 10⁹/L clonal B lymphocytes for ≥3 months, clonality and phenotype (CD5+, CD23+, CD19+, CD20 dim, kappa/lambda restricted) confirmed by flow cytometry.
  • Prognostic markers: IGHV mutated (favorable) vs unmutated; del 17p / TP53 (poor); del 11q (ATM); del 13q (favorable); CD38, ZAP-70.
  • Indications to treat (iwCLL): symptomatic, progressive marrow-failure cytopenias, bulky/progressive disease, B symptoms; AIHA/ITP only when poorly responsive to corticosteroids/standard therapy.
  • 1L: BTK-i (acalabrutinib, zanubrutinib > ibrutinib due to safety) OR ven + obinutuzumab × 12 cycles (CLL14, fixed-duration). Fit + IGHV-mut + no del(17p)/TP53 → FCR (rare now); TP53-aberrant disease gets targeted therapy, not FCR.
  • R/R: switch class (BTK-i ↔ BCL2-i). Pirtobrutinib (non-covalent BTK-i). CD19 CAR-T (lisocabtagene).
  • Richter transformation: aggressive DLBCL transformation; treat as DLBCL ± clonally-related strategies.
  • AMPLIFY (NEJM 2025, FDA Feb 2026): acalabrutinib + venetoclax (FDA-approved without obinutuzumab) fixed-duration all-oral 1L CLL/SLL (excl 17p/TP53), superior to chemoimmunotherapy; first all-oral fixed-duration frontline CLL regimen approved by the FDA (ibrutinib + venetoclax approved earlier in Europe).
  • Liso-cel (TRANSCEND CLL 004, FDA Mar 2024): first CAR-T approved for R/R CLL/SLL after at least 2 prior lines including a BTK inhibitor and a BCL2 inhibitor.

Lymphomas: quick reference

Hodgkin lymphoma
  • Reed-Sternberg cells (CD15+, CD30+, CD20−).
  • Subtypes: nodular sclerosis (most common), mixed cellularity, lymphocyte-rich, lymphocyte-depleted, NLPHL (CD20+, treat differently).
  • Early-stage: ABVD × 2 to 4 + ISRT (RAPID, HD16, etc.). (S1826 applies to advanced stage III to IV cHL: nivolumab-AVD was superior to brentuximab-AVD; it did not test BV-AVD plus nivolumab and is not an early-stage regimen.)
  • Advanced: S1826: nivolumab + AVD × 6 (new SOC). Or escalated BEACOPP (Europe).
  • Refractory/relapsed: pembrolizumab (KEYNOTE-204), brentuximab, salvage chemo + autoSCT.
NHL
  • DLBCL: R-CHOP × 6 (POLARIX: pola-R-CHP improved PFS). High-risk: dose-adjusted EPOCH-R for double-hit. CAR-T (axi-cel ZUMA-7, liso-cel TRANSFORM 2L per high-risk).
  • CNS prophylaxis for high IPI/CNS risk score (HIV+, testicular, kidney/adrenal, double-hit): IT MTX or HD-MTX.
  • Follicular lymphoma: watch and wait if asymptomatic; R-bendamustine, R-CHOP. Mosunetuzumab (CD20×CD3 bispecific antibody), tisagenlecleucel CAR-T, axi-cel.
  • MCL: BTK-i, ven, lenalidomide. CAR-T (brexu) for relapsed.
  • Marginal zone: MALT (H. pylori), splenic, nodal. Antibiotics for H. pylori-positive MALT.
  • Burkitt: very aggressive, rapid TLS. R-CODOX-M / IVAC, DA-EPOCH-R.
  • Primary CNS lymphoma: HD-MTX + rituximab → autoSCT or WBRT.
  • PTCL: CHOEP. Brentuximab for ALK+ ALCL. Belinostat, pralatrexate for relapsed (romidepsin still used but its US PTCL indication was withdrawn 2021).
  • Cutaneous T-cell lymphoma (mycosis fungoides, Sezary): skin-directed therapy → mogamulizumab, romidepsin, brentuximab.

Multiple myeloma

Treatment map for multiple myeloma: D-VRd induction, autologous transplant and maintenance for transplant-eligible patients; D-Rd or quadruplet Isa-VRd or D-VRd for transplant-ineligible patients; triplet or quadruplet combinations at relapse; BCMA CAR-T, bispecific antibodies and belantamab mafodotin in later lines including penta-refractory disease.
Myeloma therapy by line, from quadruplet induction to BCMA- and GPRC5D-directed therapy (IMROZ, NEJM 2024). Tap to enlarge.
  • Diagnosis (CRAB): hyperCa, renal, anemia, bone lesions. SLiM-CRAB adds: ≥60% clonal marrow plasma cells; involved:uninvolved serum FLC ratio ≥100 (involved FLC ≥100 mg/L); >1 focal MRI lesion, each ≥5 mm.
  • Standard 1L (transplant-eligible): Dara-RVd induction → autoSCT → maintenance lenalidomide. (D-VRd per PERSEUS: quadruplet improved PFS).
  • Standard 1L (transplant-ineligible): D-Rd, or quadruplet Isa-VRd (IMROZ) or D-VRd (CEPHEUS) in fit patients; DVRd-lite option.
  • Maintenance: lenalidomide ± daratumumab.
  • Relapsed / refractory: triplet/quad combinations. Carfilzomib, pomalidomide, isatuximab, selinexor, elotuzumab.
  • Advanced / penta-refractory:
    • CAR-T (BCMA): ide-cel (KarMMa), cilta-cel (CARTITUDE-1, -4; even earlier-line approval).
    • Bispecific (BCMA, GPRC5D): teclistamab, elranatamab, talquetamab, linvoseltamab.
    • Belantamab mafodotin: BCMA ADC (re-approved by FDA Oct 2025 as Bela-Vd per DREAMM-7).
    • IMROZ (Facon NEJM 2024, FDA Sep 2024): Isa-VRd for newly dx TIE MM: superior PFS vs VRd (5-yr PFS 63% vs 45%). Quad becomes new standard for TIE, parallel to PERSEUS for TE.
    • CEPHEUS (FDA Jan 2026): Dara-VRd for newly dx TIE / transplant-deferred MM; sustained MRD-neg superior. Expanded Dara-VRd from TE to TIE.
    • Belantamab RE-APPROVED (Oct 2025): Bela-Vd (DREAMM-7) for R/R MM after ≥2 prior lines incl. a PI and an IMiD; Bela-Pd (DREAMM-8) not FDA-approved. Ocular toxicity REMS.
    • Bone disease: bisphosphonate or denosumab. Spine MRI for cord compression.
    • Renal: avoid nephrotoxic chemo; dose-adjust lenalidomide.

Plasma cell disorders

Diagram of the plasma cell spectrum from MGUS (about 1% per year progression) to smoldering myeloma (observe or treat early; SC daratumumab for high risk) to active myeloma (CRAB or SLiM criteria), with boxes for AL amyloidosis, Waldenström macroglobulinemia and POEMS.
MGUS, smoldering and active myeloma with defining features, plus AL amyloidosis, Waldenström macroglobulinemia and POEMS. Tap to enlarge.
  • MGUS: monitor; ~1%/yr progression to MM.
  • Smoldering MM: observe vs early intervention (lenalidomide ↓ progression). High-risk SMM: SC daratumumab monotherapy FDA-approved Nov 2025 (AQUILA, first approved SMM therapy).
  • AL amyloidosis: light chain deposition. Dara + CyBorD (ANDROMEDA). Cardiac/renal involvement common.
  • Waldenström macroglobulinemia (LPL): MYD88 L265P. BTK-i (ibrutinib, zanubrutinib).
  • POEMS: polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes. Treat plasma cell clone.

High-yield heme pearls

  • APL: ATRA + ATO; differentiation syndrome → dex.
  • Ven + aza for older/unfit AML.
  • CLL 1L: BTK-i or ven + obinutuzumab.
  • S1826: nivo + AVD new SOC for advanced HL.
  • POLARIX: pola-R-CHP for DLBCL (PFS, not OS).
  • CAR-T 2L DLBCL (ZUMA-7, TRANSFORM): for high-risk relapse <12 mo.
  • PERSEUS / D-VRd quadruplet for transplant-eligible MM.
  • Cilta-cel CARTITUDE-4: earlier-line MM approval.
  • Asciminib 1L CML (ASC4FIRST 2024).
Veli Bakalov MD, Board Review Notes 2026