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NCCN Flash Updates: NCCN Guidelines Updated for Acute Lymphoblastic Leukemia

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®), the NCCN Radiation Therapy Compendium™, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™) for Acute Lymphoblastic Leukemia. These NCCN Guidelines^® are currently available as Version 1.2024.

Link directly to the Updates section of the NCCN Guidelines: Acute Lymphoblastic Leukemia

Global Changes

• References updated throughout Guideline

ALL-1

• Classification
  • Bullet modified: Together, these studies allow determination of the World Health Organization (WHO) and International Consensus Criteria (ICC) ALL subtypes and cytogenetic and clinical risk groups.

ALL-1A

• Footnote c modified: T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LBL) subtypes include T-ALL/T-LBL, not otherwise specified (NOS), cortical type, mature type, and early T-cell precursor (ETP) lymphoblastic leukemia/lymphoma; ETP-ALL typically lacks expression of CD5, CD8, and CD1a and expression of one or more myeloid/stem cell markers. The mature subtype often also lacks expression of CD1a and frequently is accompanied by T-ALL11 or T-ALL12 rearrangement.

ALL-4

• Workup
  • 5th bullet modified: Hepatitis B/C, human immunodeficiency virus (HIV), cytomegalovirus (CMV) Ab testing

ALL-5

• Treatment Induction
  • Adolescents and young adults (AYAs) and adults <65 years without substantial comorbidities
    • New therapy option added: TKI + blinatumomab
  • Adults ≥65 years or with substantial comorbidities
    • New therapy option added: TKI + blinatumomab
• Consolidation Therapy, Persistent/Rising MRD:
  • New therapy option added: Inotuzumab ozogamicin ± TKI
  • Top pathway modified: Consider allogeneic hematopoietic cell transplantation (HCT)

ALL-5A

• Footnote gg added: Prior to blinatumomab initiation, cytoreduce with TKI + corticosteroid to peripheral WBC count of <10 x 10⁹/L. Foà R, et al. N Engl J Med 2020;383:1613-1623.
• Footnote ll modified: Although long-term remission after blinatumomab + TKImonotherapy is possible, allogeneic HCT canshould be considered as consolidative therapy
• Footnote mm added: Blinatumomab + TKI is preferred in consolidation regardless of MRD status for those who have not previously received blinatumomab.
• Footnote nn added: Although there are limited data, the Panel recommends waiting at least 4 weeks from the completion of inotuzumab ozogamicin monotherapy and the start of conditioning therapy for allogeneic HCT to minimize risk of sinusoidal obstruction syndrome (SOS). SOS occurred less frequently when fewer alkylators were used as part of the conditioning regimen. Kantarjian H, et al. Cancer 2013;119:2728-2736. (Also for ALL-6A)
• Footnote pp modified: Optimal timing of allogeneic HCT is not clear. For fit patients, additional therapy is recommended to eliminate MRD prior to transplant. Proceeding to allogeneic HCT with MRD is not optimal. (Also for ALL-6A, ALL-7)
• Footnote uu modified: Consider sequentialperiodic MRD monitoring (no more than every 3 months) for patients with complete molecular remission (undetectable levels). Increased frequency may be indicated for detectable levels or for those discontinuing TKI.
• Footnote removed: For patients who are not candidates for multiagent therapy.

ALL-6

• Page extensively revised

ALL-6A

• Footnote ww modified: If MRD is unavailable, consider retesting for MRD at first available opportunity.
• Footnote yy added: Blinatumomab is preferred for those with persistent or rising MRD who have not previously received blinatumomab.
• Footnote zz modified: ECOG1910 included patients aged 30–70 years, but multiagent therapy with blinatumomab as consolidation can be considered in AYA patients.Blinatumomab should be incorporated into frontline therapy as a post-remission approach based on data from ECOG1910.
• Footnote aaa modified: Although long-term remission after blinatumomab monotherapy is possible, allogeneic HCT canshould be considered as consolidative therapy

ALL-9A

• Footnote fff modified: Isolated extramedullary relapse (includingboth CNS and testicular) requires systemic therapy to prevent relapse in marrow. Consider CNS prophylaxis for relapsed/refractory disease. The role of CNS prophylaxis in the setting of cellular therapy is still being studied.
• Footnote kkk modified: The role of allogeneic HCT following cellular therapytisagenlecleucel is unclear. Persistence of tisagenlecleucel in peripheral blood and persistent B-cell aplasia has been associated with durable clinical responses without subsequent HCT. In the global registration trial, relapse-free survival was 59% at 12 months, with only 9% of patients proceeding to HCT.
• Footnote lll modified: For patients in late relapse (>3 years from initial diagnosis), consider treatment with the same induction regimen (for Ph-negative B-ALL, see ALL-D 10 of 28; for T-ALL, see ALL-D 19 of 28; for Treatment of Adults ≥65 years or Adults with Substantial Comorbidities, see ALL-D 4 of 9).

ALL-C 1 of 4

• Best Supportive Care
  • 6th bullet removed and moved to ALL-C 2 of 4: Consider defibrotide for patients who develop veno-occlusive disease (VOD) related to inotuzumab ozogamicin toxicity.

ALL-C 3 of 4

• Asparaginase Toxicity Management
  • 4th bullet modified: All toxicity grades refer to CTCAE v5.04.03.
  • 6th bullet added: Consider anticoagulation prophylaxis if no contraindications.
• Hypersensitivity, Allergy, and Anaphylaxis
  • 1st bullet modified: ERW-rywn shouldmay be used as a second-line agent in patients who have developed a systemic allergic reaction or anaphylaxis due to PEG hypersensitivity.
  • 2nd bullet modified: Anaphylaxis or other allergic reactions of Grade 3–4 severity (CTCAE v5.04.03) merit permanent discontinuation of the type of asparaginase that caused the reaction.
• Footnote a added: In the setting of AYA/Adult ALL, Cal-PEG is substituted for PEG in patients aged 15 to ≤21 years for more sustained asparaginase activity.
• Footnote c modified: National Institutes of Health; National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) version 5.020174.03 2010. Available at: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm

ALL-C 4 of 4

• Non-CNS Thromboembolism
  • 1st bullet modified: For Grade 2 or greater thromboembolic event, hold asparaginase until resolved and treat with appropriate antithrombotic therapy. Upon resolution of symptoms and antithrombotic therapy stable or completed, consider resuming asparaginase.

ALL-D

• Section extensively revised

ALL-E 1 of 2

• Page extensively revised

For the complete updated versions of the NCCN Guidelines, NCCN Guidelines with NCCN Evidence Blocks™, the NCCN Drugs & Biologics Compendium (NCCN Compendium^®), the NCCN Biomarkers Compendium^®, the NCCN Chemotherapy Order Templates (NCCN Templates^®), the NCCN Radiation Therapy Compendium™, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™), please visit NCCN.org.

To view the NCCN Guidelines for Patients^®, please visit NCCN.org/patientguidelines.

Free NCCN Guidelines apps for iPhone, iPad, and Android devices are now available! Visit NCCN.org/apps.

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