06/06/2017

NCCN has published updates to the NCCN Guidelines and the NCCN Compendium® for Acute Lymphoblastic Leukemia

NCCN has published updates to the NCCN Guidelines and NCCN Drugs & Biologics Compendium (NCCN Compendium^®) for Acute Lymphoblastic Leukemia. These NCCN Guidelines are currently available as Version 1.2017.  

• Diagnosis (ALL-1)
  • Bullet 3 added: Baseline characterization of leukemic clone to facilitate subsequent MRD analysis
  • Genetic Characterization
    • Bullet 3 modified: Reverse transcriptase-polymerase chain reaction (RT-PCR) testing for fusion genes (eg, BCR-ABL1) in B-ALL (quantitative or qualitative) including determination of transcript size (ie, p190 vs. p210)
  • Footnote “a” modified: Subtypes: B-cell lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities include hyperdiploidy, hypodiploidy, and commonly occurring translocations: t(9;22)(q34.1;q11.2)[BCR-ABL1]; t(v;11q23.3)[MLL KMT2A rearranged]; t(12;21)(p13.2;q22.1)[ETV6-RUNX1]; t(1;19)(q23;p13.3)[TCF3-PBX1]; t(5;14)(q31;q32)[IL3-IGH;relatively rare]. B-cell lymphoblastic leukemia/lymphoma, not otherwise specified. T-cell lymphoblastic leukemia/lymphoma. Provisional entities: B-lymphoblastic leukemia/lymphoma, BCR-ABL1–like; B-lymphoblastic leukemia/lymphoma with iAMP21; Early T-cell precursor lymphoblastic leukemia.
  • Footnote "e" added: The following immunophenotypic findings are particularly notable: CD10 negativity correlates with KMT2A rearrangement; ETP T-ALL; CD20 positivity: definition not clear, most studies have used >20% of blasts expressing CD20. See Discussion.

• Workup and Risk Stratification (ALL-2)
  • Bullet 5 added: Urinalysis
  • Bullet 6 added: Hepatitis B/C, HIV, CMV Ab testing
  • Bullet 7 added: Pregnancy testing, fertility counseling and preservation
  • Bullet 9 modified: Lumbar puncture (LP) with IT chemotherapy
  • Bullet 10 modified: CT of neck/chest/abdomen/pelvis with IV contrast and PET/CT if lymphomatous involvement is suspected (for patients with T-ALL) For patients with a mediastinal mass, baseline PET imaging is also recommended.
  • Bullet 12; sub-bullet 1 modified and combined with sub-bullet 2: Screen for active opportunistic infections if febrile or for symptomatic opportunistic infections. Initiate empirical treatment, as appropriate (See NCCN Guidelines for Prevention and Treatment of Cancer-Related Infections)
  • Bullet 15 modified: Consider human leukocyte antigen (HLA) typing (except for patients with a major contraindication to hematopoietic cell ransplan [HTC]) and Consider early evaluation and search for an family or an alternative donor
  • Risk stratification modified with removal of age criteria for AYA and Adults.
  • Footnote "k" added: The ALL panel considers AYA to be within the age range of 15–39 years. However, this age is not a firm reference point because some of the recommended regimens have not been comprehensively tested across all ages.

• Ph+ ALL (AYA): Treatment and Consolidation Therapy (ALL-3)
  • Induction
    • TKIs + corticosteroids added as a treatment option.
  • Footnote “s” added: Optimal timing of HCT is not clear. For fit patients, additional therapy may be considered to eliminate MRD prior to transplant. (also applies to ALL-4, ALL-5, ALL-7)
  • Footnote “u” added: Duration of post-HCT or maintenance TKI should be a minimum of a year. The optimal duration is unknown. (also applies to ALL-4)
  • Footnote “v” added: Consider periodic MRD monitoring (no more than every 3 months) for patients with complete molecular remission (undetectable levels). Increased frequency may be indicated for detectable levels. (also applies to ALL-4)

• Ph- ALL (AYA): Treatment and Consolidation Therapy (ALL-5)
  • Treatment induction:
    • "Preferred" removed from pediatric-inspired regimens
    • "Other" removed before multiagent chemotherapy.
  • Consolidation therapy modified after CR with addition of MRD assessment categories
    • Persistent or late clearance MRD+: Blinatumomab (B-ALL) or Consider allogeneic HCT
    • MRD-: Continue multiagent chemotherapy or Consider allogeneic HCT (especially if high WBC or B-ALL with poor-risk cytogenetics)
    • MRD unknown: Allogeneic HCT (especially if high WBC or B-ALL with poor-risk cytogenetics) or Consider continuing multiagent chemotherapy followed by maintenance therapy
  • Footnote "aa" added: Although long-term remission after blinatumomab treatment is possible, allogeneic HCT should be considered as consolidative therapy.

• Ph- ALL (Adult): Treatment and Consolidation Therapy (ALL-6)
  • Patients ≥65 years of age or with substantial comordibities
    • Monitoring for MRD added after CR

• Consolidation Therapy for patients <65 years of age without substantial comorbidities (ALL-7)
  • Consolidation therapy modified after CR with addition of MRD assessment categories
    • Persistent or late clearance MRD+: Blinatumomab (B-ALL) or Consider allogeneic HCT
    • MRD-: Continue multiagent chemotherapy or Consider allogeneic HCT (especially if high WBC or B-ALL with poor-risk cytogenetics)MRD unknown: Allogeneic HCT (especially if high WBC or B-ALL with poor-risk cytogenetics) or Consider continuing multiagent chemotherapy followed by maintenance therapy

• Surveillance (ALL-8)
  • Timing intervals removed from sub-bullets for CBC and LFTs
  • Bullet 2: "every 3–6 months" added
  • Bullet 3: "every 6–12 months or as indicated" added
  • Bullet 5 added: Periodic BCR-ABL1 transcript-specific quantification (Ph+ ALL)

• Relapsed/Refractory Disease (ALL-9)
  • Allogeneic HCT alone removed
  • Ph+ ALL
    • "Consider ABL gene mutation testing" changed to "ABL1 kinase domain mutation testing"
    • "Consider" removed before clinical trial
    • "HCT" added after treatment with TKI ± chemotherapy and TKI ± corticosteroids
    • Blinatumomab added as a treatment option after failure of 2 TKIs
  • Ph- ALL
    • "Consider" removed before clinical trial
    • "HCT" added after treatment with chemotherapy
    • Blinatumomab added as a treatment option. This is a category 1 recommendation.

• Induction regimens for Ph+ ALL (ALL-D 1 of 5)
  • Protocols for AYA patients
    • Bullet 3 modified with addition of ponatinib as a TKI option
    • Bullet 4 modified with addition of nilotinib as a TKI option
    • Bullet 5 added: TKIs (imatinib, dasatinib, nilotinib) + corticosteroids
    • Bullet 6 added: TKIs (imatinib, dasatinib, nilotinib) + vincristine + dexamethasone
  • Adult patients
    • Bullet 1 modified with addition of ponatinib as a TKI option
    • Bullets 2 and 3 modified with addition of nilotinib as a TKI option
    • Bullet 4 modified with specification of TKIs imatinib, dasatinib, nilotinib
  • Maintenance regimens
    • Bullet 1 modified with nilotinib and ponatinib added as TKI options
    • Footnote "b" added: These regimens are used for induction therapy and additional therapy is needed.

• Induction regimens for Ph- ALL (ALL-D 2 of 5)
  • AYA patients
    • Categories of "pediatric-inspired protocols" and "other chemotherapy protocols" replaced with "Regimens based on data from multi-institutional or cooperative group studies" and "Regimens based on data from single institution studies"
      • Regimens based on data from multi-institutional or cooperative group studies
        • "With rituximab for CD20-positive disease" added to GRAALL regimen
      • Regimens based on data from single institution studies
        • Linker 4-drug regimen added as a treatment option
  • Adult patients
    • GRAALL regimen with rituximab for CD20-positive disease added as a treatment option
  • Maintenance regimen
    • Duration of "2–3 years" replaced with "duration based on regimen"
  • Footnote "e" added: There are data to support the benefit of rituximab in addition to chemotherapy for CD20-positive patients (especially in patients <60 years).

• Regimens for Relapsed/Refractory ALL (ALL-D 3 of 5)
  • A table added with Treatment Options Based on BCR-ABL1 Mutation Profile.
  • Footnote "g" added: The safety of relapsed/refractory regimens in older adults (≥65) has not been established. Please see ALL-E 5 of 5 for additional information.
  • Ph-positive ALL
    • "Preferred" removed after the following TKI options: dasatinib, imatinib, ponatinib.
    • Bosutinib added as a treatment option.
    • Blinatumomab added as a treatment option after failure of 2 TKIs.
    • The following regimen added: MOpAD regimen: methotrexate, vincristine, pegaspargase, dexamethasone; with rituximab for CD20-positive disease. This is a category 2B recommendation.
  • Ph-negative ALL
    • "Preferred" removed after blinatumomab. Category designation changed from a category 2A to a category 1.
    • The following regimen added: MOpAD regimen: methotrexate, vincristine, pegaspargase, dexamethasone; with rituximab for CD20-positive disease

• NEW PAGE: Treatment of Older Adults with ALL (ALL-D 5 of 5)

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.