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
Dr. Joseph Delano Fule Robles, 06 May 2019

Gilteritinib, a novel inhibitor of the tyrosine kinase FLT3, improves survival outcomes among patients with relapsed or refractory acute myeloid leukaemia (AML) with FLT3 mutations vs standard chemotherapy, according to results of the phase III ADMIRAL trial reported at the American Association for Cancer Research (AACR) Annual Meeting 2019 held in Atlanta, Georgia, US.

Roshini Claire Anthony, 30 Apr 2019

Patients with advanced small cell lung cancer (SCLC) who experience disease progression despite two or more lines of therapy could benefit from pembrolizumab in the third-line setting, according to results from the phase 1b KEYNOTE-028 and phase II KEYNOTE-158* studies presented at AACR 2019.