08/23/2017

NCCN has published updates to the NCCN Guidelines® and the NCCN Compendium® for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®), and the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. These NCCN Guidelines^® are currently available as Version 1.2018. 

• New algorithm
  • A new algorithm was added for Histologic Transformation (Richter's) and Progression.
• Workup (CSLL-2)
  • The following recommendations were moved from Essential to Useful Under Certain Circumstances
    • Hepatitis B testing if treatment contemplated.
    • MUGA scan/echocardiogram if anthracycline- oranthracenedione-based regimen is indicated
    • Pregnancy testing in women of child-bearing age (if systemic therapy or RT planned).
• Supportive Care
• Tumor lysis syndrome (TLS) (CSLL-C 2 of 4)
  • 5^th bullet regarding the first-line and at retreatment for hyperuricemia, the first sub-bullet was revised, "Allopurinol or febuxostat beginning 2–3 days prior to chemotherapy and continued for 10–14 days."
• A new section was added for "Cancer Screening: Standard screening guidelines should be closely followed for breast, colon, and prostate cancers." (CSLL-C 3 of 4)
• Suggested treatment regimens
  • First-line therapy for CLL/SLL without del(17p)/TP53 mutation (CSLL-D 1 of 5)
    • For frail patients with significant comorbidity (not able to tolerate purine analogs)
      • High-dose methylprednisolone (HDMP) + rituximab was added as a category 2B recommendation.
    • For age ≥65 y and younger patients with significant comorbidities
      • Bendamustine ± rituximab was changed to Bendamustine ± CD20 monoclonal antibody.
      • HDMP + rituximab was added as a category 2B recommendation.
    • For age <65 y without significant comorbidities
      • The order of preference was revised.
      • HDMP + rituximab was added as a category 2B recommendation.
      • PCR (pentostatin, cyclophosphamide, rituximab) was changed from a category 2A to a category 3 recommendation.
      • Bendamustine ± rituximab was changed to Bendamustine ± CD20 monoclonal antibody.
    • Footnotes
      • Footnote d was revised by adding, "CD20 monoclonal antibodies include: rituximab, ofatumumab, or obinutuzumab."
      • Footnote e was added, "Minimal residual disease (MRD) evaluation in blood with 10^-4 sensitivity according to standardized ERIC method.") Also for CSLL-D 2 of 5 and 3 of 5).
      • Footnote h was added, "Rituximab and hyaluronidase human injection for subcutaneous use may be used for CLL in combination with fludarabine and cyclophosphamide (FC) regimen after patients have received at least one full dose of a rituximab product by intravenous route." Also for CSLL-D 2 of 5.
  • Relapsed/refractory therapy for CLL/SLL without del(17p)/TP53 mutation (CSLL-D 2 of 5)
    • For both frail patients with significant comorbidity or age ≥65 y and younger patients with significant comorbidities
      • The order of preference was revised.
      • Bendamustine ± rituximab was changed to bendamustine + rituximab and added to bullets for ibrutinib and idelalisib as follows along with the dosing for bendamustine
      • Bendamustine (70 mg/m² in cycle 1 with escalation to 90 mg/m² if tolerated), rituximab ± ibrutinib (category 2B). This recommendation was changed from a category 3 to a category 2B recommendation.
      • Bendamustine (70 mg/m² in cycle 1 with escalation to 90 mg/m² if tolerated), rituximab ± idelalisib (category 3).
    • For age <65 y without significant comorbidities
      • The order of preference was revised.
      • RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) was removed.
      • OFAR (oxaliplatin, fludarabine, cytarabine, rituximab) was removed. 
  • First-line therapy for CLL/SLL with del(17p)/TP53 mutation (CSLL-D 3 of 5)
  • Obinutuzumab + chlorambucil (category 3) was changed to obinutuzumab monotherapy with a category 2A recommendation.
  • • Relapsed/refractory therapy for CLL/SLL with del(17p)/TP53 mutation (CSLL-D 3 of 5)
      • OFAR (oxaliplatin, fludarabine, cytarabine, rituximab) was removed.
    • Special Considerations for the Use of Small-Molecule Inhibitors (Ibrutinib and Idelalisib)
      • For ibrutinib, Last bullet was revised, "Testing for BTK and PLCG2 mutations may be useful to identify patients receiving ibrutinib potentially at risk for clinical depression in patients receiving ibrutinib and suspected of having progression. BTK and PLCG2 mutation status alone is not an indication to change treatment." (CSLL-F 1 of 2)