eBulletin Newsletter

NCCN Flash Updates: NCCN Guidelines^® and NCCN Compendium^® Updated for Acute Myeloid Leukemia

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®), NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™), and the NCCN Drugs and Biologics Compendium (NCCN Compendium^®) for Acute Myeloid Leukemia (AML). These NCCN Guidelines^® are currently available as Version 1.2021.

Acute Myeloid Leukemia

• Evaluation for Acute Leukemia (EVAL-1)
  • Bullet 4 modified: Bone marrow (BM) core biopsy and aspirate analyses, including immunophenotyping and cytochemistry by immunohistochemistry (IHC) stains + flow cytometry
  • Bullet 6 modified: Molecular analyses (ASXL1, c-KIT, FLT3 [ITD and TKD], NPM1, CEBPA (biallelic), IDH1, IDH2, RUNX1, TP53, and other mutations.
• Diagnosis; AML (EVAL-1)
  • To appropriately stratify available intensive therapy options, expedite test results of molecular and cytogenetic analyses (maximum 3–5 days) for immediately actionable mutations
  • Bullet 1 modified: For patients with highly proliferative cancers hyperleukocytosis uncontrolled with hydroxyurea or leukapheresis, one dose of intermediate-dose cytarabine (1–2 gm) may be considered prior to receiving results
  • Bullet added: For patients who prefer not to receive blood transfusion(s), see AML-D for general considerations and supportive care.
  • Bullet removed: Appropriate management of leukocytosis is recommended while awaiting cytogenetic and molecular test results.
• Footnotes for EVAL-1 (EVAL-1A)
  • Footnote a modified; second and fourth sentences: Other mutations genetic lesions, such as ASXL1, BCR-ABL, and PML-RAR alpha (See AML-A) may have therapeutic implications. The field of genomics in myeloid malignancies, and related implications in AML, are evolving rapidly. While the above mutations should be tested in all patients, multiplex gene panels and comprehensive next-generation sequencing analysis are recommended for a comprehensive prognostic assessment the ongoing management of AML and various phases of treatment.
  • Footnote b modified with removal of the following (which is represented on AML-B): For patients with major neurologic signs or symptoms at diagnosis, appropriate imaging studies should be performed to detect meningeal disease, chloromas, or CNS bleeding. LP should be performed if no mass lesion is detected on the imaging study with central shift making an LP relatively contraindicated. Screening LP should be considered at first remission before first consolidation for patients with monocytic differentiation, mixed phenotype acute leukemia (MPAL), WBC count >40,000/mcL at diagnosis, extramedullary disease, or high-risk APL.
• APL Treatment Induction and Consolidation Therapy (Low Risk) (APL-2)
  • After induction with preferred regimens, monitoring recommendations modified:
    • If blood count recovery by day 28 (platelet >100,000, ANC >1,000), proceed with consolidation. BM aspirate and biopsyday 28–35 (if cytopenic) may be considered to document morphologic remission but is optional.
    • If full course of induction treatment not given, or counts have not recovered by day 28–35, a BM aspirate and biopsy is recommended to document morphologic remission before proceeding with consolidation.
  • Consolidation Therapy modified for 2nd preferred regimen:
    • ATRA 45 mg/m² for 2 weeks every 4 weeks (or for 2 weeks on 2 weeks off) in consolidation courses 1–4 + arsenic trioxide 0.3 mg/kg IV on days 1–5 of week one in consolidation courses 1–4 and 0.25 mg/kg twice weekly in weeks 2–4 in consolidation courses 1–4 (category 1)
      
      replaced with
    • First 3 consolidation cycles = 56-day cycles: ATRA 45 mg/m²/d PO divided into 2 daily doses on days 1–14 and 29–42 (2 weeks on followed by 2 weeks off) + arsenic trioxide 0.3 mg/kg on days 1–5 of week 1 followed by 0.25 mg/kg twice weekly during weeks 2–4
      4th consolidation cycle = 28 day cycle: ATRA 45 mg/m²/d PO divided into 2 daily doses on days 1–14 (2 weeks on followed by 2 weeks off) + arsenic trioxide 0.3 mg/kg on days 1–5 of week 1 followed by 0.25 mg/kg twice weekly during weeks 2–4
  • Other Recommended changed to Useful in Certain Circumstances (if contraindications to arsenic is not available or contraindicated)
    • Regimen added
      • Induction: ATRA 45 mg/m² in 2 divided doses daily + a single dose of gemtuzumab ozogamicin 9 mg/m² on day 5
      • Consolidation: ATRA 45 mg/m² in divided doses daily during weeks 1–2, 5–6, 9–10, 13–14, 17–18, 21–22, and 25–26. A single dose of gemtuzumab ozogamicin 9 mg/m² may be given monthly until 28 weeks from CR
• Footnotes for APL-2 (APL-2A)
  • Footnote k added: Estey et al. Blood 2002;99:4222-4224.
• APL Treatment Induction and Consolidation Therapy (High Risk) in Patients with Cardiac Issues (APL-4)
  • APL Treatment Induction (High Risk) in Patients with Cardiac Issues; Prolonged QTc
    • Regimens added
      • Induction: ATRA 45 mg/m² in 2 divided doses + daunorubicin 60 mg/m² x 3 days + cytarabine 200 mg/m² x 7 days
      • Consolidation: Daunorubicin 60 mg/m² x 3 days + cytarabine 200 mg/m² x 7 days x 1 cycle, then cytarabine 2 g/m² (age <50) or 1.5 g/m² (age 50–60) every 12 h x 5 days + daunorubicin 45 mg/m² x 3 days x 1 cycle + 5 doses of intrathecal (IT) chemotherapy
        
        or
      • Induction: ATRA 45 mg/m² in 2 divided doses + idarubicin 12 mg/m2 on days 2, 4, 6, 8
      • Consolidation: ATRA 45 mg/m² x 15 days + idarubicin 5 mg/m² and cytarabine 1 g/m² x 4 days x 1 cycle, then ATRA x 15 days + mitoxantrone 10 mg/m²/d x 5 days x 1 cycle, then ATRA x 15 days + idarubicin 12 mg/m² x 1 day + cytarabine 150 mg/m² over 8 h x 4 days x 1 cycle
• Principles of Supportive Care for APL (APL-A)
  • APL differentiation syndrome; sub-bullet 3 modified: The following cytoreduction strategies for leukocytosis may be used for differentiation syndrome that is difficult to treat: cytoreduction, hydroxyurea, anthracycline, gemtuzumab ozogamicin.
  • Arsenic trioxide monitoring; sub-bullet 2, diamond 3 added: In patients with prolonged QTc interval >500 millisec, correct electrolytes and proceed with caution. QTcF is recommended; however, in settings where QTcF corrections are unavailable, a cardiology consult may be appropriate for patients with prolonged QTc.
  • Reference 3 added: Sanz MA, Fenaux P, Tallman MS, et al. Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet. Blood 2019;133:1630-1643.
• AML Physiologic Age <60 y; Treatment Induction (AML-1)
  • Age clarified as physiologic age (applies throughout AML section)
  • Favorable-risk cytogenetics
    • Preferred noted for standard-dose cytarabine with daunorubicin and gemtuzumab ozogamicin (CD33-positive)
    • Regimen added: Fludarabine 30 mg/m² IV days 2–6, HiDAC 2 g/m² over 4 hours starting 4 hours after fludarabine IV on days 2–6, idarubicin 8 mg/m² IV on days 4–6, and granulocyte colony-stimulating factor (G-CSF) subcutaneously (SC) daily days 1–7 plus a single dose of gemtuzumab ozogamicin 3 mg/m² in first course (category 2B)
  • Category added for Unfavorable risk cytogenetics and TP53-mutated
    • Alternative induction strategies should be considered
  • Other recommended regimens for intermediate- or poor-risk disease
    • Regimen removed: Standard dose cytarabine with daunorubicin and cladribine
    • HiDAC regimen modified with a dose change for daunorubicin from 60 to 50 mg and the addition of etoposide 50 mg/m² days 1–5
• Footnotes for AML-1 (AML-1A)
  • Footnote f added: Consider referral to palliative care for consultation at the start of induction. LeBlanc T, et al. Curr Hematol Malig Rep. 2017;12:300-308 and LeBlanc T, et al. J Oncol Pract. 2017;13:589-590. See NCCN Guidelines for Palliative Care. (also applies to AML-2A, AML-3, AML-5A, AML-6A, AML-7)
  • Footnote g added: See General Considerations and Supportive Care for AML Patients who Prefer not to receive Blood Transfusions (AML-D). (also applies to AML-6A)
  • Footnote o modified: There are limited data supporting the use of this regimen in patients aged <60 years. Lancet JE, et al. J Clin Oncol 2018;36:2684-2692.
  • Footnote s added: Willemze R, et al. J Clin Oncol 2014;32:219-228.
  • Footnote removed: Holowiecki J, et al. J Clin Oncol 2012;30:2441-2448. Although this trial showed an advantage for the addition of cladribine to standard 7+3, BM aspirates were not performed after the first cycle of induction until either counts recovered or blasts reappeared in the peripheral blood, which would delay administration of a second cycle of induction compared to standard practice in the United States.
• Footnotes for AML-2 (AML-2A)
  • Footnote v added: There are limited prospective data to support this recommendation. Othus M, et al. Leukemia 2016;30:1779-1780. (also applies to AML-7)
  • Footnote removed: For patients with residual blasts after induction with standard-dose cytarabine with daunorubicin and cladribine, a second cycle of the same induction regimen can be given if >50% cytoreduction.
• AML Physiologic Age <60 y; Post-Remission/Maintenance Therapy (AML-4)
  • Risk status categories modified
    • CBF cytogenetic translocations without KIT mutation and MRD negative
    • Intermediate-risk cytogenetics and/or molecular abnormalities, including MRD positive
• Footnotes for AML-4 (AML-4A)
  • Footnote ff modified: Burnett AK, et al. J Clin Oncol 2011;29:369-377. Meta-analyses showing an advantage with gemtuzumab ozogamicin have included other dosing schedules. Hills RK, et al. Lancet Oncol 2014;15:986-996. (also applies to AML-5A, AML-8A)
• Footnotes for AML-5 (AML-5A)
  • Footnote ll modified: There is a web-based scoring tool available to evaluate the probability of complete response and early death after standard induction therapy in elderly patients with AML: http://www.aml-score.org/. Krug U, et al. Lancet 2010;376:2000-2008. A web-based tool to predict CR and early death can be found at: https://www.fhcrc-research.org/TRM/Default.aspx?GUID=1358501B-C922-4422-84F0-0E6C67D8F266 and Walter RB, et al. J Clin Oncol. 2011;29:4417-4423. Factors in decisions about fitness for induction chemotherapy include age, performance status, functional status, and comorbid conditions. See NCCN Guidelines for Older Adult Oncology. (also applies to AML-6A)
  • Footnote mm added: Patients with TP53 mutations are a group with poor prognosis, and should be considered for enrollment in clinical trials.
  • Footnote nn added: Castaigne S, et al. Lancet 2012;379:1508-1516.
  • Footnote rr modified: This regimen may be continued for patients who demonstrate clinical improvement (CR/CRi), with consideration of subsequent transplant, where appropriate. DiNardo CD, et al. Lancet Oncol 2018;19:216-228. Wei A, et al. Blood 2017;130:890. Wei A, et al. Haematologica 2017; Abstract S473. DiNardo CD, Blood 2019;133:7-17. DiNardo CD, et al. N Engl J Med 2020;383:617-629. (also applies to AML-6A, AML-9)
  • Footnote tt added: Wei AH, et al. J Clin Oncol 2019;37:1277-1284. (added to AML-6A, AML-9)
  • Footnote vv added: Regimens that include gemtuzumab ozogamicin have limited benefit in patients with poor-risk disease.
• AML Physiologic Age ≥60 y; Treatment Induction (AML-6)
  • Regimens noted as preferred or other recommended
    • AML without actionable mutations
      • Venetoclax and azacitidine noted as category 1 and preferred
      • Venetoclax and decitabine noted as preferred
      • LDAC dosing added: 20 mg/m²/day SC for 10 consecutive days every 4 weeks
    • IDH1 of IDH2 mutation or FLT3 mutation
      • Venetoclax-based therapy with azacitidine noted as category 1 and preferred
      • Venetoclax-based therapy with decitabine noted as preferred
• Footnotes for AML-6 (AML-6A)
  • Footnote ww modified: This regimen is for treatment of newly diagnosed AML in patients who are ≥75 years of age, or who have significant comorbid conditions (ie, severe cardiac disease, ECOG performance status ≥2, baseline creatinine >1.3 mg/dL) and has been associated with an improved OS in a randomized trial.
  • Footnote yy added: Regimens that include gemtuzumab ozogamicin will not benefit patients with poor-risk disease.
  • Footnote zz added: Kantarjian HM, et al. J Clin Oncol 2012;30:2670-2677.
  • Footnote aaa modified: DiNardo CD, et al. Blood 2017;130:725; DiNardo CD, et al. Blood 2017;130:639; Roboz GJ, et al. Blood 2020;135:463-471. (also appiles to AML-9)
  • Footnote ddd added: Ohanian M, et al. Am J Hematol 2018;93:1136-1141. (also applies to AML-9)
  • Footnote removed: Ravandi F, et al. Blood 2013;121:4655-4662. (also applies to AML-9)
• AML Physiologic Age ≥60 y; After Standard-Dose Cytarabine Induction (AML-7)
  • Treatment option modified: Reduced-intensity Consider allogeneic HCT
  • Footnote eee modified: Reduced-intensity Allogeneic transplant is a reasonable option in patients who experience failure after re-induction with certain regimens (eg, intermediate- or high-dose cytarabine), and have with identified donors available to start conditioning within 4–6 weeks from start of induction therapy. Patients without an identified donor would most likely need some additional therapy as a bridge to transplant. Reduced-intensity HCT may be appropriate for patients with a low level of residual disease post-induction (eg, patients with prior MDS who reverted back to MDS with <10% blasts). It is preferred that this approach be given in the context of a clinical trial. For patients with residual disease after 1 cycle of induction chemotherapy who would not tolerate another intensive salvage, consider a venetoclax-based regimen.
• AML Physiologic Age ≥60 y; Post-Remission/Maintenance Therapy (AML-8)
  • Complete response
    • Treatment option modified: Intermediate-dose cytarabine 1–1.5 g/m² over 3 h every 12 h on days 1, 3, and 5 or 1 g/m² over 3 h every 12 h on days 1, 3, 5 (total 6 doses) for a total of 4 planned cycles with oral midostaurin 50 mg every 12 h on days 8–21
• Footnotes for AML-8 (AML-8A)
  • Footnote iii modified: Alternate administration of intermediate-dose cytarabine may also be used. Sperr WG, et al. Clin Cancer Res. 2004;10:3965-3971. The RATIFY trial studied patients aged 18–60 y. An extrapolation of the data suggests that older patients who are fit to receive 7+3 should be offered midostaurin since it seems to provide a survival benefit without undue toxicity. Schlenk RF, et al. Blood 2019;133:840-851.
  • Footnote jjj modified: An option for patients who had achieved a remission with a more intensive regimen but had regimen-related toxicity that prevented them from receiving more conventional consolidation. Huls G, et al. Blood. 2019;133:1457-1464.
  • Footnote removed: An excellent outcome was reported for outpatient consolidation that provides another option for elderly patients. Gardin C, et al. Blood 2007;109:5129-5135.
• AML Surveillance and Therapy for Relapsed/Refractory Disease (AML-10)
  • Testing recommendations at relapse modified
    • Determine mutation status of actionable genes: FLT3 (ITD or TKD); IDH1; IDH2
      
      changed to
    • Comprehensive genomic profiling to determine mutation status of actionable genes
  • Footnote nnn modified: Comprehensive molecular profiling (including IDH1/IDH2, FLT3 mutations) is suggested as it may assist with selection of therapy and appropriate clinical trials (see Discussion). Molecular testing should be repeated at each relapse or progression.
  • Footnote ooo modified: Reinduction therapy may be appropriate in certain circumstances, such as in patients with long first remission (an exception is there are no data regarding re-induction with dual-drug liposomal encapsulation of cytarabine and daunorubicin). This strategy primarily applies to cytotoxic chemotherapy and excludes the re-use of targeted agents due to the potential development of resistance. Targeted therapies may be retried if agents were not administered continuously and not stopped due to development of clinical resistance. If a second complete response is achieved, then consolidation with allogeneic HCT should be considered.
• New section: Familial Genetic Alteration in AML (AML-A 2 of 3 and AML-A 3 of 3)
• Evaluation and Treatment of CNS Leukemia (AML-B)
  • Footnote 2 modified: For patients with major neurologic signs or symptoms at diagnosis, appropriate imaging studies should be performed to detect meningeal disease, chloromas, or CNS bleeding. LP should be performed if no mass, lesion, or hemorrhage was detected on the imaging study with central shift making an LP relatively contraindicated.
  • Footnote 3 modified: Screening LP should be considered at first remission before first consolidation for patients with monocytic differentiation, mixed phenotype acute leukemia (MPAL), WBC count >40,000/mcL at diagnosis, extramedullary disease, high-risk APL, or FLT3 mutations. For further information regarding MPAL, see NCCN Guidelines for Acute Lymphoblastic Leukemia.
• New section: General Considerations and Supportive Care for AML Patients who Prefer not to Receive Blood Transfusions (AML-D)
• Principles of Supportive Care for AML (AML-E)
  • General; Blood products
    • Sub-bullet 2 modified: Irradiated blood products for patients receiving immunosuppressive therapy (ie, fludarabine, HCT). All AML patients are at risk for acute graft-versus-host disease (aGVHD) and management should be based on institutional practice/preference.
  • General; Tumor lysis prophylaxis
    • Sub-bullet added: Glucose-6-phosphate dehydrogenase (G6PD) deficiency should be checked when possible. However, it is not always feasible to do so rapidly. If there high suspicion of G6PD deficiency, caution is necessary; rasburicase may be contraindicated.
• Measurable (Minimal) Residual Disease Assessment (AML-G)
  • Bullet 3 modified: The most frequently employed methods for MRD assessment include real-time quantitative polymerase chain reaction (RQ-PCR) assays (ie, NPM1, CBFB-MYH11, RUNX1-RUNX1T1), next-generation sequencing (NGS)–based assays to detect mutated genes (targeted sequencing, 20–50 genes per panel), and multicolor flow cytometry (MFC) assays specifically designed to detect abnormal MRD immunophenotypes. The threshold to define MRD+ and MRD- samples depends on the technique and subgroup of AML. Next-generation sequencing (NGS)–based assays to detect mutated genes (targeted sequencing, 20–50 genes per panel) is not routinely used, as the sensitivity of PCR-based assays and flow cytometry is superior to what is achieved by conventional NGS. Mutations associated with clonal hematopoiesis of indeterminate potential (CHIP) and aging (ie, DNMT3A, TET2, potentially ASXL1) are also not considered reliable markers for MRD.
    • Sub-bullet 1 modified: There are distinct differences between diagnostic threshold assessments and MRD assessments. If using flow cytometry to assess MRD, it is recommended that a standard specific MRD assay is utilized, but, most importantly, that it is interpreted by an experienced hematopathologist.
  • Bullet 4 modified: Based on the techniques, the optimal sample for MRD assessment is either peripheral blood (NPM1 PCR-based techniques) or an early, dedicated pull of the BM aspirate (ie, other PCR, flow cytometry, NGS). The quality of the sample is of paramount importance to have reliable evaluation.
  • Bullet 5
    • Sub-bullet removed: A negative MRD result after induction, which depends on the technique used and the study, predicts a lower incidence of relapse.
    • Sub-bullet 2 modified: For favorable-risk patients, if MRD is persistently positive after induction and/or consolidation, consider a clinical trial or alternative therapies, (eg, including allogeneic transplantation, consolidation).
      • Diamond 1 removed: Patients with t(8;21) AML in remission may have a persistently positive PCR result, which may not indicate relapse.
    • Sub-bullet 3 added: Some evidence suggest MRD testing may be more prognostic than KIT mutation status in CBF AML, but this determination depends on the method used to assess MRD and the trend of detectable MRD.
  • Reference 6 added: Morita K, Kantarjian H, Wang F, et al. Clearance of somatic mutations at remission and the risk of relapse in acute myeloid leukemia J Clin Oncol 2018;36:1788-1797.
• Response Criteria Definitions for Acute Myeloid Leukemia (AML-H)
  • Bullet 1; Morphologic leukemia-free state
    • Sub-bullet 1 modified: BM <5% blasts in an aspirate with spicules; at least 200 cells must be enumerated
  • Bullet 2: Complete response;
    • Morphologic CR; Diamond 3 modified: No residual evidence of extramedullary diseaseNo blasts with Auer rods or persistence of extramedullary disease
    • Sub-bullet 2 added: CR without MRD (CRMRD-).
      • Diamond 1 added: If studied pretreatment, CR with negativity for a genetic marker by RQ-PCR or CR with negativity by MFC
      • Diamond 2 added: Sensitivity varies by marker and method used; analyses should be done in experienced laboratories
    • Sub-bullet removed: Cytogenetic CR - cytogenetics normal (in those with previously abnormal cytogenetics)
    • Sub-bullet 3 added: CRh - partial hematologic recovery, defined as < 5% blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts (platelets > 50 × 10⁹/L and ANC > 0.5 × 10⁹/L)
    • Sub-bullet 4 modified: CR with incomplete hematologic recovery (CRi) - There are some clinical trials that include a variant of CR referred to as CRi. This has been defined as <5% marrow blasts, either ANC <1000/mcL or platelets <100,000/mcLAll CR criteria and transfusion independence but with persistence of cytopenia (usually neutropenia (<1,000/mcL) and thrombocytopenia (<100,000/mcL).
  • Bullet 5 modified: Induction failure - Failure to attain CR or CRi following exposure to at least 2 courses of intensive induction therapy (2 cycles of 7+3 or one cycle of 7+3 and one cycle of HiDAC).
  • Footnote 1 modified: Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol 2003;21:4642-4649. Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 2017;129:424-447.
  • Footnote 2 modified: This is clinically relevant only in APL and Ph+ leukemia, and failure to achieve a significant reduction (eg >3 log) in molecular evidence of t(8;21) or inv(16) has a very high predictive value of relapse at the present time. Molecular remission for APL should be performed after consolidation, not after induction as in non-APL AML. NPM1 is a target that can be included in the molecular response assessment. Ivey A, et al. N Engl J Med 2016;374:422-433.
  • Footnote 3 added: Bloomfield CD, Estey E, Pleyer L, et al. Time to repeal and replace response criteria for acute myeloid leukemia? Blood Rev 2018;32:416-425.
• Therapy for Relapsed/Refractory Disease (AML-I)
  • Aggressive therapy for appropriate patients
    • Regimen modified: Clofarabine ± cytarabine + G-CSF ± idarubicin
  • Footnote 8 modified: Wierzbowska A, Robak T, Pluta A, et al. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol 2008;80:115-126. Robak T, Wrzesień-Kuś A, Lech-Marańda E, et al. Combination regimen of cladribine (2-chlorodeoxyadenosine), cytarabine and G-CSF (CLAG) as induction therapy for patients with relapsed or refractory acute myeloid leukemia. Leuk Lymphoma 2000;39:121-129.
  • Footnote 10 added: Karanes C, Kopecky KJ, Head DR, et al. A phase III comparison of high dose ARA-C (HIDAC) versus HIDAC plus mitoxantrone in the treatment of first relapsed or refractory acute myeloid leukemia Southwest Oncology Group Study. Leuk Res 1999;23:787-794.
  • Footnote 13 modified: Amadori S, Arcese W, Isacchi G, et al. Mitoxantrone, etoposide, and intermediate-dose cytarabine: an effective and tolerable regimen for the treatment of refractory acute myeloid leukemia. J Clin Oncol 1991;9:1210-1214. Nair G, Karmali G, Gregory SA, et al. Etoposide and cytarabine as an effective and safe cytoreductive regimen for relapsed or refractory acute myeloid leukemia. J Clin Oncol 2011; 29:15_suppl, 6539-6539.
• New section: Principles of Venetoclax Use With HMA or LDAC-Based Treatment (AML-J 1 of 2 and AML-J 2 of 2)

Blastic Plasmacytoid Dendritic Cell Neoplasm

• Treatment Induction (BPDCN-2)
  • Candidate for intensive remission induction therapy; Treatment Induction
    • Tagraxofusp-erzs noted as preferred (also applies to BPDCN-3)
    • Chemotherapy: AML and ALL induction clarified as AML- and ALL-type induction chemotherapy.
  • Patients with low performance and/or nutritional status
    • Localized/isolated cutaneous disease
      • Treatment options clarified as palliative
    • Systemic disease
      • Treatment option added: Venetoclax-based therapy
  • Footnote i added: Pemmaraju N, et al. Blood 2019;134(Supplement_1):2723.
  • Footnote s added: DiNardo CD, et al. Am J Hematol 2018;93:401-407. (also applies to BPDCN-3)
• Principles of Supportive Care for BPDCN (BPDCN-B)
  • Administration/management of toxicities associated with tagraxofusp-erzs
    • Bullet 3; sub-bullet 2 modified: Administer tagraxofusp-erzs at 12 mcg/kg IV over 15 minutes once daily on days 1–5 of a 21-day cycle. Alternately, 5 doses can be administered over a 10-day period, if needed for dose delays.

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