multiple%20myeloma
MULTIPLE MYELOMA

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 & prognosis

Smoldering (Asymptomatic) Myeloma

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

Active Multiple Myeloma

  • Induction therapy followed by high-dose chemotherapy w/ autologous stem cell transplantation is recommended for young patients without comorbidities
  • Combination regimens with ≥3 agents is preferred over 2-drug regimens
    • Treatment w/ 2-drug regimens may be considered for elderly & frail patients

Pharmacotherapy

  • Induction therapy depends on patient's eligibility for stem cell transplant

Preferred Regimens for SCT-Eligible Patients

Bortezomib-Based Combinations

  • Eg Bortezomib/Lenalidomide/Dexamethasone (RVD), Bortezomib/Cyclophosphamide/Dexamethasone (VCD), Bortezomib/Thalidomide/Dexamethasone (VTD)
  • 3-drug Bortezomib-based regimens 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 w/ acute renal insufficiency
    • Bortezomib/Thalidomide/Dexamethasone (VTD)
      • Option for primary treatment of SCT-eligible multiple myeloma patients, but under certain circumstances (3-drug regimen preferred)
      • Showed significantly higher CR rates, near CR rates, VGPR, & overall response rate (ORR) in several studies when compared to the Bortezomib-free 2-drug regimen Thalidomide/Dexamethasone
      • Thromboprophylaxis is recommended during use
  • Herpes prophylaxis is recommended in patients receiving Bortezomib-based chemotherapeutic combinations

Lenalidomide/Dexamethasone

  • Approved for the treatment of relapsed/refractory multiple myeloma patients
  • Option for primary treatment of SCT-eligible multiple myeloma patients, but under certain circumstances (ie elderly or frail patients)

Other Recommended Regimens for SCT-Eligible Patients

  • Bortezomib/Doxorubicin/Dexamethasone (PAD)
    • A category 1 option for primary treatment of transplant-eligible multiple myeloma 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, & treatment option for newly diagnosed multiple myeloma patients

Conditional Regimens for SCT-Eligible Patients

  • Bortezomib/Dexamethasone
    • Option for primary treatment of SCT-eligible multiple myeloma patients, but under certain circumstances eg renal impairment
    • Showed significantly higher ORR, CR/near remission (NR) & VGPR when compared to Vincristine/Doxorubicin/Dexamethasone (VAD), w/ lesser hematologic side effects
    • Also showed good efficacy rates in high-risk patients w/ ISS stage III disease & poor-risk cytogenetic abnormalities 
  • Bortezomib/Dexamethasone/Thalidomide/Cisplatin/Doxorubicin/Cyclophosphamide/Etoposide (VTD-PACE)
    • Treatment option for newly diagnosed transplant-eligible multiple myeloma patients w/ high-risk & aggressive extramedullary disease or plasma cell leukemia

Preferred Regimens for SCT-Ineligible Patients

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

Other Recommended Regimens for SCT-Ineligible Patients

  • Carfilzomib/Lenalidomide/Dexamethasone w/ or without either Lenalidomide or Cyclophosphamide
    • 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 
  • Bendamustine/Prednisone regimen may be considered for patients w/ suspected or confirmed neuropathy prior to initiation of MPT or VMP therapy

Conditional Regimen for SCT-Ineligible Patients

  • Bortezomib/Dexamethasone
    • Primary therapeutic option for patients under certain circumstances for transplant-ineligible multiple myeloma patients 
  • Bortezomib/Melphalan/Prednisone (VMP) & Melphalan/Prednisone/Thalidomide (MPT) are approved by the European Medicines Agency (EMA) for use in elderly patients w/ multiple myeloma not eligible for SCT

Maintenance Therapy

Lenalidomide

  • 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 & safety of Lenalidomide maintenance therapy after allogeneic SCT

Bortezomib

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

Observation & 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, & 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 w/ confirmed MGUS or smoldering myeloma

Stem Cell Transplanation

Autologous Stem Cell Transplant (ASCT)

  • Preferred management strategy for younger patients w/ newly diagnosed multiple myeloma, combined w/ chemotherapy
  • Early front-line treatment w/ ASCT is preferred & showed improved PFS compared to conduction of ASCT during disease relapse
  • Transplant conducted early during the course of the disease is associated w/ longer event-free survival rates & 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 w/ 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, & during disease relapse

Allogeneic Stem Cell Transplant (Allo-SCT)

  • Includes myeloablative & nonmyeloablative transplant
    • Myeloablative allo-SCT may be considered in multiple myeloma patients whose disease is responsive to primary therapy, w/ primary disease progression, or those w/ 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 & associated w/ reduced disease relapse brought about by its graft-versus-myeloma effect
  • Limited by scarcity of compatible donors & increased morbidity
  • Not recommended for patients w/ newly diagnosed disease outside of a clinical trial, w/ the exception of young patients w/ 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
4 days ago
New drug applications approved by US FDA as of 01 - 15 June 2019 which includes New Molecular Entities (NMEs) and new biologics. It does not include Tentative Approvals. Supplemental approvals may have occurred since the original approval date. 
Audrey Abella, 5 days ago
The taxane-based TPEx regimen demonstrated encouraging overall survival (OS) benefit for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) compared with the fluorouracil (5FU)-based EXTREME regimen, according to the results of the TPExtreme* trial presented at ASCO 2019.