Multiple myeloma is a bone marrow disease characterized by the presence of malignant plasma cells, & abnormal serum &/or urine immunoglobulin secondary to clonal plasma cell expansion.

It accounts for 1-2% of all cancers worldwide & mostly affects patients at ages 65-74 years old.

Patient usually presents with bone pain & nonspecific symptoms, or due to abnormalities in laboratory exams.


Principles of Therapy

  • Distinguishing active multiple myeloma from other types of multiple myeloma is imperative for proper management planning and prognosis

Smoldering (Asymptomatic) Myeloma

  • Therapeutic management is not needed but observation and routine follow-up is recommended
  • Patients with high-risk smoldering multiple myeloma may consider joining clinical trials

Active Multiple Myeloma

  • Induction therapy followed by high-dose chemotherapy with autologous stem cell transplantation is recommended for young patients without comorbidities
  • Combination regimens with ≥3 agents is preferred over 2-drug regimens
    • Treatment with 2-drug regimens may be considered for patients ineligible for triple therapy, and may consider adding a 3rd agent once performance status improves


  • Induction therapy depends on patient's eligibility for stem cell transplant (SCT)
    • For SCT-eligible patients, combination of a proteasome inhibitor, an immunomodulatory drug, plus Dexamethasone is the preferred regimen prior to transplant
      • Cyclophosphamide may be considered if immunomodulatory drug is unavailable
      • Agents known to be associated with stem-cell toxicity should be avoided in SCT-eligible patients: Melphalan,>1 year Thalidomide therapy
    • For SCT-ineligible patients, combination of a proteasome inhibitor or an immunomodulatory drug, plus a steroid is preferred 
      • Studies showed improved treatment response rates, longer progression-free survival, and improved overall survival with triple therapy 

Preferred Regimens for SCT-eligible Patients

Bortezomib-based Combinations

  • 3-drug Bortezomib-based regimens Bortezomib/Lenalidomide/Dexamethasone (RVD) and Bortezomib/Cyclophosphamide/Dexamethasone (VCD) are the preferred primary therapy for SCT-eligible patients
    • Bortezomib/Lenalidomide/Dexamethasone is the preferred option for primary treatment of transplant-eligible multiple myeloma patients
    • Bortezomib/Cyclophosphamide/Dexamethasone (VCD) is the preferred option for transplant-eligible multiple myeloma patients with acute renal insufficiency
  • Herpes prophylaxis is recommended in patients receiving Bortezomib-based chemotherapeutic combinations

Other Recommended Regimens for SCT-eligible Patients

  • Carfilzomib/Lenalidomide/Dexamethasone (KRd)
    • Option for primary treatment of SCT-eligible multiple myeloma patients
  • Ixazomib/Lenalidomide/Dexamethasone
    • Primary regimen for patients who previously received at least 1 prior therapy, and treatment option for newly diagnosed multiple myeloma patients

Conditional Regimens for SCT-eligible Patients

  • Options for primary treatment of SCT-eligible multiple myeloma patients, but under certain circumstances:
    • Bortezomib/Doxorubicin/Dexamethasone (PAD)
    • Bortezomib/Thalidomide/Dexamethasone (VTD)
      • Showed significantly higher CR rates, near CR rates, VGPR, and overall response rate (ORR) in several studies when compared to the Bortezomib-free 2-drug regimen Thalidomide/Dexamethasone
      • Thromboprophylaxis is recommended during use
    • Cyclophosphamide/Lenalidomide/Dexamethasone
    • Daratumumab/Bortezomib/Thalidomide/Dexamethasone
      • Daratumumab is given with Hyaluronidase-fihj when administered subcutaneously
    • Lenalidomide/Dexamethasone
  • Treatment options for patients with renal insufficiency and/or peripheral neuropathy
    • Carfilzomib/Cyclophosphamide/Dexamethasone
    • Ixazomib/Cyclophosphamide/Dexamethasone
  • Bortezomib/Dexamethasone/Thalidomide/Cisplatin/Doxorubicin/Cyclophosphamide/Etoposide (VTD-PACE)
    • Treatment option for newly diagnosed transplant-eligible multiple myeloma patients with high-risk and aggressive extramedullary disease or plasma cell leukemia

Preferred Regimens for SCT-ineligible Patients

  • 3-drug regimens are preferred due to higher response rates and recorded depth of response in various clinical studies
    • Bortezomib/Lenalidomide/Dexamethasone (VRd)
      • Studies showed significantly improved PFS and OS compared to Rd alone 
    • Bortezomib/Cyclophosphamide/Dexamethasone (VCD)
      • Preferred treatment option for SCT-ineligible multiple myeloma patients with acute renal insufficiency
      • May consider switching to 3-drug regimen Bortezomib/Lenalidomide/Dexamethasone once renal function normalizes 
    • Daratumumab/Lenalidomide/Dexamethasone
      • Daratumumab is given with Hyaluronidase-fihj when administered subcutaneously
  • 2-drug chemotherapeutic regimens should only be considered in elderly and frail patients
    • Lenalidomide/low-dose Dexamethasone (Rd)
      • Preferred option for SCT-ineligible elderly or frail multiple myeloma patients with standard-risk features
      • Thromboprophylaxis is recommended during use
      • Continuous treatment is recommended until disease progression occurs 

Other Recommended Regimens for SCT-Ineligible Patients

  • Carfilzomib/Lenalidomide/Dexamethasone
    • Option for primary treatment of newly diagnosed multiple myeloma patients not qualified for SCT 
  • Ixazomib/Lenalidomide/Dexamethasone
    • Primary treatment option for newly diagnosed multiple myeloma patients not qualified for SCT 
  • Daratumumab/Bortezomib/Melphalan/Prednisone
    • Treatment option for primary treatment of transplant-ineligible multiple myeloma patients
    • Daratumumab is given with Hyaluronidase-fihj when administered subcutaneously
  • Bendamustine/Prednisone regimen may be considered for patients with suspected or confirmed neuropathy prior to initiation of MPT or VMP therapy

Conditional Regimen for SCT-ineligible Patients

  • Bortezomib/Dexamethasone (VD)
    • Primary therapeutic option for patients under certain circumstances for transplant-ineligible multiple myeloma patients 
  • Carfilzomib/Cyclophosphamide/Dexamethasone
    • Treatment option for patients with renal insufficiency and/or peripheral neuropathy
  • Cyclophosphamide/Lenalidomide/Dexamethasone
    • Therapeutic option for patients under certain circumstances for transplant-ineligible multiple myeloma patients
  • Bortezomib/Melphalan/Prednisone (VMP) and Melphalan/Prednisone/Thalidomide (MPT) are approved by the European Medicines Agency (EMA) for use in elderly patients with multiple myeloma not eligible for SCT

Maintenance Therapy


  • Recommended as maintenance therapy after autologous SCT in newly-diagnosed multiple myeloma patients
    • May also be considered as maintenance therapy in patients ineligible for SCT, but benefits should be weighed against reported adverse events (eg neutropenia, secondary malignancy) 
  • Studies showed reduced risk of disease progression or mortality, but often accompanied by grade 3-4 neutropenia
  • Further studies are needed to prove the use and safety of Lenalidomide maintenance therapy after allogeneic SCT

Bortezomib with or without Lenalidomide

  • May be considered as maintenance therapy after autologous SCT and in multiple myeloma patients who were not eligible for transplant
  • Studies have shown improved response rates with maintenance Bortezomib


  • May be considered as maintenance therapy after autologous SCT

Observation and Follow up

Smoldering (Asymptomatic) Myeloma

  • Initiation of treatment in early-stage disease is not recommended
  • Re-evaluation every 3-6 months is advised
  • Repeat CBC, serum creatinine, albumin, calcium, serum quantitative immunoglobulins, SPEP, SIFE, serum FLC assay, 24-hour urine assay for total protein, UPEP, and UIFE should be conducted every follow-up if clinically indicated
  • Imaging studies (eg skeletal survey or WBLD-CT, MRI, PET-CT) may be done if clinically indicated
  • Multiparameter flow cytometry may effectively predict the risk of disease progression in patients with confirmed MGUS or smoldering myeloma

Stem Cell Transplanation

Autologous Stem Cell Transplant (ASCT)

  • Preferred management strategy for younger patients with newly diagnosed multiple myeloma, combined with chemotherapy
  • Early front-line treatment with ASCT is preferred and showed improved PFS compared to conduction of ASCT during disease relapse
  • Transplant conducted early during the course of the disease is associated with longer event-free survival rates and improved quality of life
  • Further studies are needed to compare the therapeutic effects of ASCT in multiple myeloma patients over chemotherapy

Tandem Stem Cell Transplant

  • Defined as undergoing repeat SCT with high-dose chemotherapy within 6 months after the 1st course
  • A 2nd ASCT may be considered in patients who did not achieve a VGPR or better following their 1st ASCT, and during disease relapse

Allogeneic Stem Cell Transplant (Allo-SCT)

  • Includes myeloablative and nonmyeloablative transplant
    • Myeloablative allo-SCT may be considered in multiple myeloma patients whose disease is responsive to primary therapy, with primary disease progression, or those with disease progression after initial ASCT
    • Nonmyeloablative is preferred over myeloablative allo-SCT due to the lesser adverse effects from the high-dose chemotherapeutic regimen
    • Avoids the contamination of re-infused autologous tumor cells and associated with reduced disease relapse brought about by its graft-versus-myeloma effect
  • Limited by scarcity of compatible donors and increased morbidity
  • Not recommended for patients with newly diagnosed disease outside of a clinical trial, with the exception of young patients with high-risk prognostic factors
Digital Edition
Asia's trusted medical magazine for healthcare professionals. Get your MIMS Oncology - Malaysia digital copy today!
Sign In To Download
Editor's Recommendations
Most Read Articles
Christina Lau, 20 Apr 2020

Hippocampal avoidance during whole-brain radiotherapy (HA-WBRT), together with memantine, better preserves cognitive function vs WBRT plus memantine in patients with brain metastases, without compromising survival, a multi-institutional phase III trial has shown.

Natalia Reoutova, 20 May 2020

Cancer patients infected with coronavirus disease 2019 (COVID-19) appear to be at higher risk of severe outcomes, including death, but cancer type and treatment serve as better predictors, according to recent research presented at the American Association for Cancer Research (AACR) 2020 Virtual Annual Meeting I.

At the time of writing, COVID-19 has spread to more than 200 countries and territories, affecting an estimated 4.5 million people and killing over 300,000. Cancer, on the other hand, is newly diagnosed in 18 million people and takes the lives of 10 million every year.

“We have invited physician scientists who are at the epicentre of the COVID-19 pandemic, taking care of patients with cancer. They gathered prospective information to understand the effects of COVID-19 on patients with cancer, are testing new treatments, and are making this knowledge available to the global research community, so we can all benefit from their experience,” said Professor Antoni Ribas from UCLA Medical Center, Los Angeles, California, US, chairperson of the COVID-19 and cancer plenary session of the meeting.

3 days ago
Case presentation: The patient is a 46-year-old Korean lady who first presented with aggravating pleuritic chest pain characterised by a stabbing pain in the chest when inhaling and exhaling. A diagnosis of non-small cell lung cancer (NSCLC) was made from computed tomography (CT)-guided needle aspiration biopsy, and the tumour was found to be epidermal growth factor receptor (EGFR) mutation-positive (exon 19 deletion). Chest imaging revealed the presence of left-sided pleural seeding nodules. The patient was treated with afatanib with partial response as best response. Ten months after starting treatment, the patient experienced disease progression.