eBulletin Newsletter

NCCN Flash Update: NCCN Guidelines Updated for Multiple Myeloma

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®), the NCCN Drugs & Biologics Compendium (NCCN Compendium^®), the NCCN Radiation Therapy Compendium™, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™) for Multiple Myeloma. These NCCN Guidelines^® are currently available as Version 1.2026.

Link directly to the Updates section of the NCCN Guidelines: Multiple Myeloma

GLOBAL

• Added new sub-section: "Considerations for Special Populations" including Older Adults and Black/African American Individuals on MYEL-F.
• Footnotes referencing MYEL-A have been changed to reflect the new title: Definitions for Myeloma and Related Plasma-Cell Disorders.

MYEL-1

• Initial Diagnostic Workup
  • Bullet 12 added: Next-generation sequencing (NGS) to assess for TP53 mutation.
• Useful in Certain Circumstances
  • Bullet 5 revised: Consider Obtain baseline clonotype identification at diagnosis and storage of or store an aspirate sample for future clonotype identification to enable minimal residual disease (MRD) testing by NGS.
  • Bullet 9 added: Renal biopsy if albuminuria or abnormal renal function.
  • Bullet removed: Single nucleotide polymorphism (SNP) array on bone marrow, and/or next-generation sequencing (NGS) panel on bone marrow.
• Clinical Findings
  • For Renal Significance, bullet added: For Monoclonal Immunoglobulin Deposition Disease (MIDD), MIDD-1.
• Footnote h added: Dimopoulos MA, et al. Lancet Oncol 2023;24:e293-e311.

MYEL-2

• Follow-Up/Surveillance
  • Bullet 5 modified: 24-h urine for total protein and UPEP with UIFE as needed.
  • Bullet removed: Tests as needed.
• Footnote k, last sentence added: Consider FISH testing on plasmacytoma biopsy if clonal cells are absent or inadequate in the marrow.
• Footnote o, last sentence modified: Patients with soft tissue and head/neck plasmacytoma could be followed less frequently as clinically indicated after initial 3-month follow-up.

MYEL-3

• Primary Treatment
  • High risk
    • Header added: Select patients.
    • Bullet 1, regimen added: Daratumumab (category 1).
    • Bullet 2, modified: Lenalidomide in select patients (category 2B).
• Follow-Up/Surveillance
  • Bullet 1, sub-bullet 5 modified: 24-h urine for total protein, UPEP, and UIFE as clinically indicated, if abnormal at baseline, or if there is significant change in FLC levels. (Also for MYEL-4).
  • Bullet 2 modified: Bone marrow aspirate and biopsy with FISH, SNP array, NGS, or multi-parameter flow cytometry as clinically indicated.
• Footnote r modified: BMPCs >20%, M-protein >2 g/dL, and serum FLC ration (FLCr) >20 are variables used to risk stratify patients at diagnosis. Patients with two or more of these factors are considered to have high risk of progression to MM. For risk criteria, refer to Lakshman A, et al. Blood Cancer J 2018;8:59 and Mateos MV, et al. Blood Cancer J 2020;10:102.
• Footnote u modified: Consider consultation for hematopoietic cell transplant (HCT) and collection of hematopoietic stem cells for future use transplant procedures.

MYEL-4

• Clinical Findings, first column, row added: For CNS disease, see CNSM-1.
• Primary treatment
  • Top row, link to NCCN Guidelines for Supportive Care added.
• Footnote x modified: See General Considerations for Myeloma Therapy(MYEL-F) for considerations for myeloma therapy and for specific populations (eg, Black/African American individuals). (Also for MYEL-5 and MYEL-6)

MYEL-5

• Response After Primary Therapy, third row modified:
  • Header added from below text: Useful in Certain Circumstances for patients with high risk of progression/relapse under certain circumstances..
• Footnote ee added: Whole-body FDG-PET/CT is recommended on day 100 after autologous HCT.
• Footnote removed: Allogeneic HCT should preferentially be done in the context of a trial when possible. (Also for MYEL-6).

MYEL-6

• Multiple Myeloma (Symptomatic)
  • First column, row added: For CNS disease, see CNSM-1.
  • Treatment column
    • Bullet 1 modified: Discuss the patient's preferences and goals of care through a shared decision-making process.
    • Bullet 2, sub-bullet 2 modified: Palliative care specialist and supportive care for symptom management (See NCCN Guidelines for Palliative Care and NCCN Guidelines for Supportive Care).
• Footnote y added: Supportive Care Treatment for Multiple Myeloma (MYEL-H).

CNSM-1

• Multiple Myeloma with CNS Disease section added.

MYEL-A

• Table reformatted.
• Definitions for solitary plasmacytoma with and without minimal marrow involvement and plasma cell leukemia added.

MYEL-B (1 of 2)

• Table reformatted.
• Column 2, row 3, bullet 2 modified: And either high-risk chromosomal abnormalities [del(17p) or translocation (4;14) or translocation (14;16)] abnormalities by FISH or Serum LDH > the ULN.
• IMS-IMWG column added.
• Reference 3 added: Avet-Loiseau H, Davies FE, Samur MK, et al. International Myeloma Society/International Myeloma Working Group Consensus Recommendations on the Definition of High-Risk Multiple Myeloma. J Clin Oncol 2025:Jco2401893.

MYEL-B (2 of 2)

• Column 1, bullet 6 added: Markers of high proliferation rate.
• Footnote moved to MYEL-A table: Presence of ≥5% of plasma cells in circulation is defined as plasma cell leukemia.

MYEL-C

• Imaging for Initial Diagnostic Workup...
  • Bullet 1 modified: Whole-body FDG-PET/CT (preferred)...
• Imaging of Solitary Plasmacytoma
  • Bullet 1, sentence 2 modified: For solitary osseous plasmacytoma, whole-body MRI (or FDG-PET/CT if MRI not available) is the first choice for initial evaluation of solitary osseous plasmacytoma.
• Imaging for Follow-up of MM
  • Bullet 1, sentence 1 modified: Advanced whole-body imaging (ie, FDG-PET/CT, low-dose CT, whole-body MRI without contrast) is recommended as needed.

MYEL-D (2 of 2)

• General Principles, bullet 6 added: For principles of RT for CNS disease in patients with MM, see Principles of Management of CNS Disease in Patients with MM (MYEL-H).

MYEL-F

• Pages extensively revised.

MYEL-G (1 of 5)

• Header revised: Primary Therapy for Transplant HCT Candidates.
  • Preferred, regimen added: Isatuximab-irfc/Bortezomib/Lenalidomide/Dexamethasone (category 1).
  • Other Recommended
    • Regimen moved from Useful in Certain Circumstances: Daratumumab/Carfilzomib/Lenalidomide/Dexamethasone.
    • Regimen moved from Useful in Certain Circumstances: Isatuximab-irfc/Carfilzomib/Lenalidomide/Dexamethasone.
• Maintenance Therapy
  • Useful in Certain Circumstances, regimen added: Daratumumab.
• Footnote c modified: See General Considerations for Myeloma Therapy(MYEL-F) for considerations for myeloma therapy and for specific populations (eg, Black/African American individuals). (Also for MYEL-G 2, 3, 4, and 5)
• Footnote removed: Preferred primarily as initial treatment in patients with acute renal insufficiency or those who have no access to proteasome inhibitor (PI)/lenalidomide/dexamethasone. Consider switching to PI/lenalidomide/dexamethasone after renal function improves. (Also for MYEL-G [2 of 5]).

MYEL-G (2 of 5)

• Header revised: Primary Therapy For if HCT Deferred or Non-Transplant Candidates if HCT is not Indicated.
• Preferred, regimen added: Daratumumab/Bortezomib/Lenalidomide/Dexamethasone (for patients <80 years old who are not frail) (category 1).
• Other Recommended
  • Regimen added: Bortezomib/Lenalidomide/Dexamethasone (category 1).
  • Regimen added: Isatuximab-irfc/Lenalidomide/Dexamethasone.
• Useful in Certain Circumstances: Regimen Added: Ixazomib/Lenalidomide/Dexamethasone.
• Footnote i added: Strongly consider collecting and storing stem cells for future HCT.

MYEL-G (4 of 5)

• Other recommended, regimen removed: Carfilzomib (twice-weekly)/dexamethasone (category 1).
• Useful in Certain Circumstances, regimen modified: Carfilzomib (weekly)/Dexamethasone (category 1).

MYEL-G (5 of 5)

• Useful In Certain Circumstances
  • Bullet 1 modified: Belantamab mafodotin-blmf (as if available through compassionate use expanded access program).
  • Bullet 3, 4, 5, 6: regimens moved from Other Recommended.

MYEL-H

• Section added: Principles of Management of CNS Disease in Patients with MM.

MYEL-I

• Footnote removed: An FDA-approved biosimilar is an appropriate substitute.

MYEL-J (1 of 2)

• Page sub-header added: For additional recommendations on infection management, see NCCN Guidelines for Prevention and Treatment of Cancer-Related Infections. (Also for MYEL-J [2 of 2])
• Common Bacterial Infections
  • Levofloxacin row, BsAb indication modified: Consider starting with therapy and administer throughout the first cycle Start when ANC <500 or per clinician discretion and continue until neutrophil recovery.
  • Immunoglobulin replacement row
    • BsAb indication modified: Consider for the duration of BsAb therapy based on clinical context.
    • Other Indications modified: For IgG <400 mg/dL and/or recurrent life-threatening infections.

MYEL-J (2 of 2)

• Common Viral and Fungal Infections
  • Pneumocystis jirovecii pneumonia (PJP) row, CAR-T and BsAb indication modified: Start with therapy and continue for at least 6 months after the infusion until end of therapy or until CD4 ≥200/mm³ (whichever is longer).

MYEL-L

• Treatment options, bullet removed: Use other plasma cell-directed therapy with caution.
• Bone-Modifying Agent Dosing in Patients with Multiple Myeloma who Have Renal Impairment Table
  • Dosing timing removed from table.
  • None row, Zoledronic Acid column entry modified: 4 mg IV every 3-4 wks 1–3 months.
• Footnote b modified: Consider other diagnosis such as amyloid and light chain disease for patients with significant proteinuria. Dimopoulos MA, et al. Lancet Oncol 2023;24:e293-e311.
• Footnote removed: An FDA-approved biosimilar is an appropriate substitute.

MIDD-1

• Monoclonal Immunoglobulin Deposition Disease section added.

POEMS-2

• Treatment
  • Bullet 3 and sub-bullets modified:
    • In patients who are not candidates for HCT transplant ineligible, options include:
      • All regimens listed above
      • Lenalidomide/dexamethasone
      • Bortezomib/Dexamethasone
      • Melphalan/Dexamethasone
      • Cyclophosphamide/Dexamethasone
      • Pomalidomide/Dexamethasone
  • Header added: Useful in Certain Circumstances
    • Bullet added: Myeloma systemic therapy options can be used in certain circumstances (see MYEL-G).