NCCN Flash Updates: NCCN Guidelines^® and NCCN Compendium^® Updated for B-Cell Lymphomas

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®), the NCCN Radiation Therapy Compendium™, and the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) for B-Cell Lymphomas. These NCCN Guidelines^® are currently available as Version 1.2021.

• Global
  • Whole-body PET/CT scan was changed to PET/CT scan (including neck).
• Diagnosis
  • 1st bullet was revised, "(...PCR for IGHV molecular analysis to detect B-cell receptor (BCR) and T-cell receptor (TCR) gene rearrangements, karyotype, and or FISH for major translocations)..." (DIAG-1)
• Follicular Lymphoma
  • Workup, Essential,
    • 8th and 9th bullets were revised from, "Chest/abdominal/pelvic (C/A/P) CT with contrast of diagnostic quality" and "Whole-body PET/CT scan essential if RT for stage I, II disease or systemic therapy is planned" to "PET/CT scan (including neck) essential if RT planned for stage I, II disease" and "PET/CT scan and/or chest/abdominal/pelvic (C/A/P) CT with contrast of diagnostic quality if systemic therapy is planned." (FOLL-2) (Also for NGMLT-1, NODE-1, MANT-1)
  • Stage I or Contiguous Stage II (FOLL-3, also for Nodal Marginal Zone Lymphoma [NODE-2])
    • Initial Therapy
      • Combined modality treatment ("ISRT + anti-CD20 monoclonal antibody ± chemotherapy [See FOLL-B]”) is now listed as a category 2A recommendation.
      • Systemic therapy alone (“Anti-CD20 monoclonal antibody ± chemotherapy [See FOLL-B]”) is included as an option in certain circumstances (eg. for patients with bulky intra-abdominal or mesenteric stage I disease)
  • Histologic Transformation to DLBCL
    • "Ibritumomab tiuxetan" was removed as a treatment option (FOLL-7; FOLL-8 and also for NODE-6)
  • First-line Consolidation or Extended Dosing (optional) (FOLL-B 1 of 5)
    • Rituximab maintenance timing was changed from "every 8–12 weeks for 12 doses" to "every 8–12 weeks for 2 years."
  • Second-line and Subsequent Therapy (FOLL-B 2 of 5)
    • Preferred regimens
      • "(not recommended if treated with prior bendamustine)" was added to "bendamustine + obinutuzumab or rituximab."
    • Other recommended regimens
      • Tazemetostat, 2nd sub-bullet was revised, "EZH2 wild type or unknown relapsed/refractory disease..."
• Marginal Zone Lymphoma (MZL)
  • First-line Extended Therapy (optional) (MZL-A 1 of 3)
    • Rituximab bullet was revised, "If initially treated with single-agent rituximab, Consolidation with rituximab 375 mg/m² one dose every 8–12 weeks for up to 2 years."
  • Second-Line and Subsequent Therapy (MZL-A 2 of 3)
    • Other recommended regimens, the following regimens were added,
      • CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) + obinutuzumab was added as a category 2B recommendation.
      • CVP (cyclophosphamide, vincristine, prednisone) + obinutuzumab was added as a category 2B recommendation.
      • Lenalidomide + obinutuzumab was added as a category 2B recommendation.
    • Footnote f was added, "Consider alternate BTKi (acalabrutinib or zanubrutinib) in patients with intolerance or contraindications to ibrutinib."
• Mantle Cell Lymphoma (MCL)
  • Induction therapy, Aggressive therapy (MANT-A 1 of 4)
    • Preferred regimens, "Rituximab, bendamustine followed by rituximab, high-dose cytarabine" was added.
  • Second-line Therapy (MANT-A 2 of 4)
    • Qualifiers, "Short response duration to prior chemotherapy (< expected median PFS)" and "Extended response duration to prior chemotherapy (> expected median PFS)" and "Partial response with intention to proceed to transplant" were removed and the regimens were reorganized.
      • "Bendamustine + rituximab + cytarabine (RBAC500) (if not previously given)" was added as a category 2A, Useful in certain circumstances recommendation.
      • Venetoclax was moved from Preferred to Useful and "± rituximab" was added.
      • Bendamustine ± rituximab (if not previously given) was moved from Preferred to Useful in certain circumstances and changed to "+ rituximab".
      • Bortezomib ± rituximab was moved from Preferred to Useful in certain circumstances.
      • Ibrutinib, lenalidomide, rituximab (category 2B) and Venetoclax + ibrutinib (category 2B) were moved from Other recommended to Useful in certain circumstances.
      • Regimens removed
        • Bendamustine, bortezomib, and rituximab (category 2B)
        • PEPC (prednisone, etoposide, procarbazine, cyclophosphamide) ± rituximab (category 2B)
        • RCHOP or VRCAP (if not previously given) (category 2B)
      • Link "See Second-line Therapy for DLBCL (BCEL-C 2 of 4) without regard to transplantability" and the regimens (ESHAP, GDP, CEOP, ICE, MINE, DA-EPOCH, gemcitabine + vinorelbine regimen) were removed and regimens from BCEL-C (DHAP, DHAX and GemOx) were added to Useful in certain circumstances.
  • "Brexucabtagene autoleucel (only given after chemoimmunotherapy and BTK inhibitor)" was clarified under a Third-line therapy heading. (MANT-A 2 of 4)
• Diffuse Large B-Cell Lymphoma (DLBCL)
  • Stage I and II, non-bulky tumors <7.5 cm (BCEL-3)
    • First-line therapy,
      • "RCHOP x 4 cycles" was added as an option.
      • "RCHOP-14 x 4–6 cycles ± ISRT" was removed as an option. Also removed from first-line therapy on BCEL-C 1 of 5.
  • Second-line and Subsequent Therapy (BCEL-C 2 of 5)
    • For non-candidates for transplant, "Polatuzumab vedotin ± bendamustine ± rituximab" was revised by removing "(after ≥2 prior therapies)."
• Burkitt Lymphoma
  • Induction Therapy <60 y (BURK-A 1 of 3)
    • Low Risk, Dose-adjusted EPOCH was revised by removing, "regimen includes intrathecal methotrexate) (Data included patients with leptomeningeal CNS disease; patients with parenchymal CNS disease were excluded in the clinical trials of this regimen.)"
    • High Risk, "Dose-adjusted EPOCH + rituximab" regimen was moved from Preferred to Other recommended regimen and the statement was revised, "(for high-risk patients with baseline CNS disease...)"
  • Second-line Therapy (BURK-A 2 of 3)
    • Dose-adjusted EPOCH, "(minimum 3 cycles with one additional cycle beyond CR)" was removed.
• AIDS-Related B-cell Lymphomas
  • DLBCL; HHV8-positive DLBCL, NOS; and PEL (AIDS-4)
    • Regimen revised, "Bortezomib-ICE ± rituximab (for DLBCL)."
• Castleman Disease
  • Multicentric Castleman Disease (Criteria for active disease present but no organ failure) (CD-3)
    • HIV-1(-) HHV8 (-)
      • Siltuximab revised by removing "(for plasmacytic/mixed histology)."
      • Thalidomide, cyclophosphamide, prednisone revised by removing "(for hyaline vascular histology)."
• Principles of Radiation Therapy
  • Volumes, ISRT for nodal disease (NHODG-D 2 of 4)
    • 5th sub-bullet was revised by adding, "Proton RT planning does not generally use a PTV, but rather robustness evaluation to ensure coverage of the CTV."
  • Volumes, ISRT for extranodal disease (NHODG-D 2 of 4)
    • 2nd sub-bullet was revised, "For most organs and particularly for indolent disease, For MALT lymphoma, the CTV generally consists of the entire affected organ (eg, stomach, salivary gland, thyroid). Partial organ ISRT may be appropriate if the disease is well localized on imaging (eg, orbit, breast, lung). For other organs, including orbit, breast, lung, bone, localized skin, and in some cases when RT is consolidation after chemotherapy, partial organ RT may be appropriate."
  • General dose guidelines, (NHODG-D 3 of 4)
    • Under 2nd sub-bullet, orbital MZL dose was added.
    • Under 4th sub-bullet, "Prophylactic testicular irradiation (25–30 Gy)" dose was added.
• Special Considerations for the Use of Small-Molecule Inhibitors
  • A bullet regarding infections was added to acalabrutinib (NHODG-E 1 of 7), ibrutinib (NHODG-E 4 of 7).
  • Zanubrutinib, infections bullet was updated to be consistent with acalabrutinib and ibrutinib. (NHODG-E 7 of 7).

NCCN has published updates to the NCCN Chemotherapy Order Templates (NCCN Templates^®) for B-cell Lymphomas to reflect the currently published NCCN Guidelines for B-Cell Lymphomas v1.2021

• The following NCCN template for Follicular Lymphoma has been DELETED:
  • FOL31: Lenalidomide
• The following NCCN templates for Mantle Cell Lymphoma have been DELETED:
  • MCL5: Bendamustine
  • MCL19: PEP-C (PredniSONE/Etoposide/Procarbazine/Cyclophosphamide)
  • MCL29: Lenalidomide
  • MCL31: PEP-C (PredniSONE/Etoposide/Procarbazine/Cyclophosphamide) + RiTUXimab
  • MCL39: Bendamustine/Bortezomib + RiTUXimab
• The following NCCN templates for Diffuse Large B-Cell Lymphoma have been deleted:
  • DBL1: Dose-Dense R-CHOP-14 (Cyclophosphamide/DOXOrubicin/VinCRIStine/PredniSONE) + RiTUXimab
  • DBL41: Dose-Dense R-CHOP-14 Cyclophosphamide/DOXOrubicin/VinCRIStine/PredniSONE) + RiTUXimab
• The following NCCN templates for Burkitt Lymphoma have been deleted:
  • BKL2: Original CODOX-M (Cyclophosphamide/VinCRIStine/DOXOrubicin/High-Dose Methotrexate)
  • BKL4: Modified CODOX-M (Cyclophosphamide/VinCRIStine/DOXOrubicin/High-Dose Methotrexate)
  • BKL5: Original CODOX-M (Cyclophosphamide/VinCRIStine/DOXOrubicin/High-Dose Methotrexate) (Cycle A) alternating with IVAC (ifosfamide/Etoposide/High-Dose Cytarabine (Cycle B) – Original CODOX-M (Cycle A) Course
  • BKL7: Modified CODOX-M (Cyclophosphamide/VinCRIStine/DOXOrubicin/High-Dose Methotrexate) (Cycle A) alternating with IVAC (ifosfamide/Etoposide/High-Dose Cytarabine (Cycle B) – Modified CODOX-M (Cycle A) Course
  • BKL9: Original or Modified CODOX-M (Cyclophosphamide/VincRIStine/DOXOrubicin/High-Dose Methotrexate) (Cycle A) alternating with IVAC (Ifosfamide/Etoposide/High-Dose Cytarabine) (Cycle B) – IVAC (Cycle B) Course

NCCN has updated the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™) to reflect recommendations within the following NCCN Guidelines:

• Penile Cancer, Version 1.2021
• Rectal Cancer, Version 1.2021
• Colon Cancer, Version 1.1021
• Genetic: Familial High-Risk Assessment: Breast and Ovarian & Pancreatic, Version 1.2020
• Genetic: Familial High-Risk Assessment: Breast and Ovarian & Pancreatic, Version 1.2021

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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