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NCCN Flash Updates: NCCN Guidelines and NCCN Templates Updated

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 1.2023.

Link directly to the Updates section of the NCCN Guidelines: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Global

• References were updated throughout the guidelines.
• Ofatumumab (monotherapy or in combination regimens) removed due to limited clinical use and availability

CSLL-1

• Diagnosis, Essential
  • 2nd bullet, 3rd sub-bullet revised: …CD10, CD200; if flow is used to establish diagnosis,…CD200 positivity may distinguish CLL from mantle cell lymphoma (MCL), which is usually CD200-.
  • 3rd bullet, 1st sub-bullet revised: …cyclin D1, LEF1, SOX11. LEF1 expression may distinguish CLL from MCL, which is usually LEF1-.
• Footnotes
  • Footnote b revised by adding: CD200 positivity may distinguish CLL from mantle cell lymphoma (MCL), which is usually CD200-.
  • Footnote d added: LEF1 and SOX11 may be helpful in suspected cases of mantle cell lymphoma that are cyclin D1-negative.

CSLL-2

• Workup
  • Essential, 5th bullet; LDH was moved from Useful Under Certain Circumstances and added as "including lactate dehydrogenase (LDH).”
  • Useful, 10th bullet revised: Discussion of fertility issues and sperm banking preservation. Corresponding footnote j added: Fertility preservation options include: sperm banking, semen cryopreservation, in vitro fertilization (IVF), or ovarian tissue or oocyte cryopreservation. (Also for HT-2)

CSLL-3

• Footnote n revised: Absolute lymphocyte count alone is not an indication for treatment since leukostasis in the absence of leukostasis, which is rarely seen in CLL.

CSLL-4

• CLL/SLL without del(17p)/TP53 mutation
  • Algorithm was extensively revised to include sequencing of therapy for relapsed or refractory disease; second- and third-line therapy options are now based on type of therapy received for first-line therapy and response to first-line therapy (CSLL-4A and CSLL-4B).

CSLL-4A

• Footnotes
  • Footnote s added: If progression with indication for subsequent therapy: Re-evaluate with FISH for del(17p)/TP53 mutation status and CpG-stimulated karyotype, prior to initiation of subsequent therapy.(Also for CSLL-4B)
  • Footnote t revised: …including if poor compliance is considered as a possible cause. BTK and PLCG2 mutation status alone is not an indication to change treatment. Alternative covalent BTKi could be considered in the setting of poor compliance or intolerance but is not a reasonable treatment option for patients with mutation in either BTK or PLCG2. (Also for CSLL-4B and CSLL-5)
  • Footnote u added: Consider the possibility of histologic transformation in patients with progressive disease. Biopsy is recommended to confirm histologic transformation. If histologic transformation or histologic progression of CLL/SLL, see HT-1.(Also for CSLL-4B)
  • Footnote v added: In patients with disease responding to therapy: Continue the same BTKi until progression and/or intolerance. If treated with venetoclax-based fixed duration treatment, observe until relapse with indications for retreatment. (Also for CSLL-4B)
  • Footnote removed: Given incurability with conventional therapy, consider including clinical trial as first-line therapy.

CSLL-4B

• Footnote x added: CIT or immunotherapy is not an option for patients who have received these regimens for first-line therapy. 

CSLL-5

• CLL/SLL with del(17p)/TP53 mutation
  • Additional therapy revised: Continue treatment with BCR pathway same BTKi until progression and/or intolerance or Observation, if treated with targeted therapy with fixed duration treatment until indication for retreatment as listed on CSLL-3 Observe until relapse with indications for treatment if treated with venetoclax + anti-CD20 mAb or other recommended immunotherapy-based regimens
  • Second-line and subsequent therapy, 2nd option revised: Consider allogeneic HCT, if without significant comorbidities in patients with CLL/SLL refractory to small-molecule inhibitor therapy relapsed or refractory disease after prior therapy with BTKi- and venetoclax-based regimen
  • Footnote z added:Consider the possibility of histologic transformation in patients with progressive disease. Biopsy is recommended to confirm histologic transformation.

CSLL-A

• Prognostic information for CLL/SLL
  • Footnote a revised: …in patients who received chemoimmunotherapy-based treatment. The significance of these prognostic variables in patients treated with targeted therapy are less well-defined.

CSLL-B 1 of 2

• Rai system, Stage 0 description revised: ...B cells and/or >40% lymphocytes in the bone marrow

CSLL-C 1 of 5

• Anti-infective Prophylaxis, 2nd bullet revised: See CSLL-F for recommended antimicrobial antiviral and PJP prophylaxis for patients receiving small-molecule inhibitor therapies.
• Treatment and Viral Reactivation, 1st bullet revised: testing for all patients receiving anti-CD20 antibody therapy

CSLL-C 2 of 5

• Treatment of TLS, First-line and at retreatment for hyperuricemia revised:
  • Glucose-6-phosphate dehydrogenase (G6PD) testing is required prior to use of rasburicase. Rasburicase is contraindicated in patients with a history consistent with G6PD. In these patients, rasburicase should be substituted with allopurinol.

Low Risk Disease: Allopurinol or febuxostat if intolerant to allopurinol beginning 2–3 days prior to chemoimmunotherapy and continued for 10–14 days

Intermediate Risk Disease: Stage I/II and LDH <2X ULN: Allopurinol or febuxostat

OR

Rasburicase if renal dysfunction and uric acid, potassium, and/or phosphate >ULN

High Risk Disease: Stage III/IV and/or LDH ≥2X ULN: Rasburicase

CSLL-C 3 of 5

• Autoimmune Cytopenias, 4th sub-bullet revised by adding: …or BTKi-based therapy for steroid-refractory or recurrent AIHA.

CSLL-C 5 of 5

• Vaccination,
  • 3rd bullet updated: Pneumococcal vaccine updated:
    • Pneumococcal polysaccharide vaccine (PPSV23) every 5 yearsor to maintain protective serologic antibody levels based on serologic testing.
    • The pneumococcal conjugate vaccine (PCV20) should be administered...Therefore, PCV7 and PCV13 should not be given with MenACWY-D but can be given with MenACWY-CRM.
  • COVID-19, 3rd sub-bullet added: Consider COVID prophylaxis with tixagevimab and cilgavimab for all patients with CLL/SLL.

CSLL-D 1 of 6

• CLL/SLL without del(17p)/TP53 mutation, First-line therapy
  • Regimens reorganized by removing qualifiers:
    • Patients age ≥65 y OR Patients age <65 years with significant comorbidities (creatinine clearance [CrCl] <70 mL/ min).
    • Patients age <65 y with significant comorbidities.
  • Ibrutinib was moved from Preferred regimens to Other recommended regimens. Corresponding footnote h added: The panel consensus to list ibrutinib under "other recommended regimens" is based on the toxicity profile. A baseline assessment of cardiac function should be done prior to initiation of ibrutinib. In patients with no intolerance, ibrutinib can be continued until disease progression.
  • Preferred regimens
    • Venetoclax + obinutuzumab was changed from a category 2A to category 1 recommendation for patients age < 65 y without significant comorbidities).
    • Zanubrutinib was changed from a category 2A to category 1 recommendation.
  • Other recommended regimens
    • Added: Ibrutinib + venetoclax as a category 2B recommendation
    • Removed the following regimens
      • Chlorambucil (category 3)
      • Rituximab (category 3)
      • FR (fludarabine + rituximab) (category 3)
  • Useful in certain circumstances
    • FCR (fludarabine, cyclophosphamide, rituximab) moved under Useful in certain circumstances with the qualifier: consider for IGHV-mutated CLL in patients age <65 y without significant comorbidities.

CSLL-D 2 of 6

• CLL/SLL without del(17p)/TP53 mutation, Second-line and Subsequent Therapy
  • Regimens were reorganized as follows:
    • Second-line therapy or third-line therapy
    • Therapy for relapsed or refractory disease after prior BTKi- and venetoclax-based regimens
  • Second-line therapy or third-line therapy
    • Ibrutinib was moved from Preferred regimens to Other recommended regimens. Corresponding footnote h added: The panel consensus to list ibrutinib under "other recommended regimens" is based on the toxicity profile. A baseline assessment of cardiac function should be done prior to initiation of ibrutinib. In patients with no intolerance, ibrutinib can be continued until disease progression.
    • Added: Retreatment with venetoclax + obinutuzumab as a category 2A recommendation under useful in certain circumstances (for relapse after a period of remission if previously used as first line therapy)
    • Removed the following regimens
      • Chlorambucil + rituximab (category 2A)
      • Alemtuzumab ± rituximab (category 3)
      • Bendamustine, rituximab + ibrutinib (category 3)
      • Dose-dense rituximab (category 3)

CSLL-D 3 of 6

• CLL/SLL with del(17p)/TP53 mutation, Second-line and Subsequent Therapy
  • First-line therapy and Second-line and subsequent therapy
    • Ibrutinib was moved from Preferred regimens to Other recommended regimens. Corresponding footnote h added: The panel consensus to list ibrutinib under "other recommended regimens" is based on the toxicity profile. A baseline assessment of cardiac function should be done prior to initiation of ibrutinib. In patients with no intolerance, ibrutinib can be continued until disease progression.
    • Other recommended regimens, added: Ibrutinib + venetoclax as a category 2B recommendation
  • Second-line and subsequent therapy, Other recommended regimens
    • Ofatumumab was removed due to limited clinical use and availability.

CSLL-E 1 of 2

• Response definitions after treatment for CLL/SLL
  • Lymph nodes, CR was revised: None ≥1.5 cm in longest dimension

CSLL-F 1 of 3

• Acalabrutinib, Drug interactions: Miscellaneous revised: Avoid co-administration of capsule formulationwith proton pump inhibitors and stagger dosing with H2-receptor antagonists and antacids; triazoles and fluoroquinolones increase drug levels.
• Footnote a revised by adding: It is safe to overlap with venetoclax while on BTKi.

CSLL-F 2 of 3

• Idelalisib
  • Most common adverse events revised by removing: abdominal pain (28%)
  • Hepatoxicity revised by removing: Discontinue if ALT/AST >20 x ULN

CSLL-F 3 of 3

• Venetoclax, drug interactions with CYP3A inhibitors updated.

ABBR-1

• New section added: Abbreviations

 

NCCN has published updates to the NCCN Guidelines and the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) for Hairy Cell Leukemia. These NCCN Guidelines are currently available as Version 1.2023.

Link directly to the Updates section of the NCCN Guidelines: Hairy Cell Leukemia

HCL-1

• Workup
  • Useful under certain circumstances, 10th bullet revised: Discussion of fertility issues and sperm bankingpreservation. Corresponding footnote g added: Fertility preservation options include: sperm banking, semen cryopreservation, in vitro fertilization (IVF), or ovarian tissue or oocyte cryopreservation.
• Footnote a revised: This guideline applies to histologically confirmed cHCL, not HCLv.

HCL-A

• Initial therapy, vemurafenib + obinutuzumab was added as category 2A, Useful in Certain Circumstances recommendation with the qualifier: consider for patients who are unable to tolerate purine analogs including frail patients and those with active infection).
• Progressive disease after relapsed/refractory therapy, Vemurafenib ± rituximab revised by adding: if not previously given.
• Footnote a revised by adding: Treatment recommendations apply to histologically confirmed cHCL, not HCLv.

HCL-E

• Ibrutinib, Adverse events of special interest updated based on Rogers KA, Andritsos LA, Wei L, et al. Phase 2 study of ibrutinib in classic and variant hairy cell leukemia. Blood 2021;137:3473-3483.

ABBR-1

• New section added: Abbreviations.

 

 

NCCN has published updates to the NCCN Chemotherapy Order Templates (NCCN Templates^®) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. These NCCN Guidelines are currently available as Version 1.2023.

• The following NCCN templates have been DELETED:
  • CLL1: Chlorambucil
  • CLL3: Chlorambucil + RiTUXimab
  • CLL14: FR (Fludarabine + RiTUXimab)
  • CLL31: RiTUXimab
  • CLL38: Dose-Dense RiTUXimab
  • CLL42: Ofatumumab
  • CLL64: Ibrutinib/Bendamustine + RiTUXimab
  • CLL67: FC (Fludarabine/Cyclophosphamide) + Ofatumumab
  • CLL71: Bendamustine + Ofatumumab

 

 

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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