Speciality
Spotlight

 




 


Oncology


 

 





Multiple
Myeloma

   

  • Wheatley
    K, for the Myeloma Trialists’ Collaborative Group [
    Radcliffe Infirmarry Oxford, England ]

    Combination Chemotherapy Versus Melphalan Plus
    Prednisone as Treatment for Multiple Myeloma : An
    Overview of 6633 Patients From 27 Randomized Trials


    J Clin Oncol 16: 3832-3842, 1998

      

    Standard induction chemotherapy for patients with
    multiple myeloma has been melphalan and prednisone [MP].
    In an effort to improve the results of M&P many
    investigators have used aggressive combined chemotherapy
    [CCT].

      

    This overview of 4930 patients and an addition 1703
    patients worldwide and from published studies were
    compared between M&P and CCT.

      

    The overview revealed no significant difference in
    survival rates associated with CCT and MP. Therefore MP
    remains the standard treatment for patients who are not
    candidates for high dose chemotherapy and autologous
    stem cell transplant. For transplant patients, the
    editor prefers vincristine, doxorubicin and
    dexamethasone as this combination provides rapid
    response and cause less toxicity to stem cells.

       

  • Singhal S, Mehta J, Desikan R, et al (Univ of South Carolina, Columbia; Univ of Arkansas, Little Rock; Rockefeller Univ, New York)

    Antitumor Activity of Thalidomide in Refractory Multiple Myeloma

    N Engl J Med 341: 1565-1571, 1999

      

    Refractory myelomas have limited therapeutic options. Bone marrow vascularization a hallmark of high plasma cell-labeling index and disease activity confers poor prognosis. Thalidomide has antiangiogenic activity. This study of 84 relapse myelomas most of whom had undergone high dose chemotherapy each one received thalidomide 200 mg/day and dose increased every 2 weeks up to 800 mg/day.

      

    The overall response rate defined as at least 25% reductions in paraprotein occurred in 32%.

      

    The common side effects included constipation, weakness or fatigue and somnolence.

       

  • Vescio R, Schiller G, Stewart AK, et al (Univ of California, Los Angeles; Toronto Hosp; Univ of South Florida, Miami; et al)

    Multicentre Phase III Trial to Evaluate CD34+ Selected Versus Unselected Autologous Peripheral Blood Progenitor Cell
    Transplantation in Multiple Myeloma

    Blood 93: 1858-1868, 1999

       

    Peripheral blood progenitor are the preferred source of autografts due to quicker restoration of hematopoiesis and procedure of harvesting is possible without general anesthesia.

      

    This study of 131 patients of multiple myeloma were randomized to CD34 selected or unselected autologous transplant myeloablative therapy.

      

    The CD34 selection could decrease 3.1 log in the number of contaminating tumor cells and there was no significant difference in platelet engraftment.

      

    Although this could not translate into an improvement in outcome or a decrease in relapse as most of the relapses are due to untreated endogenous tumor and not due to contamination of tumor cell.

           

  • Jean-Luc Harousseau (Service D’Hematologie Clinique, Nantes, France)

    International Myeloma Grand Round

    Current Status of High-Dose Chemotherapy


    The Lancet Oncology September 2001 Vol. 2 (9) Pg. 572-573

       

    The French cooperative group, have randomised patients of multiple myeloma to conventional chemotherapy followed by interferon, to conventional chemotherapy followed by high dose therapy (HDT) with 140 mg/m2 of melphalan plus total body irradiation (TBI) followed by autologous bone-marrow transplantation and interferon.

      

    The HDT group had 22% patient in CR and 16% have a very good partial remission compared with 14% in conventional arm survival is longer in those who achieve CR.

      

    A comparison of the French regimen of melphalan 140 mg/m2 plus TBI with that of Royal Marsden regimen melphalan 200 mg/m2 revealed higher toxic side effects with French regimens, 3.6% toxicity related death in radiotherapy group and overall survival was also better with Royal Marsden regimen which was due to better salvage therapy at the time of relapse.

       

    Barlogie and colleagues have revealed improved CR with repeated courses of melphalan and two autologous transplantation. The French study also inferred that in those patient it was feasible to do two transplants with blood, had better complete and very good partial remission.

      

    The prognostic factors identified in patients treated with HDT are detection of chromosome 13 by FISH and high b2-microglobulin levels.

       

  • Gregory R. Mundy (University of Texas Health Science Center, Texas, USA)

    International Myeloma Grand Round

    Investigation, Prophylaxis, and Treatment of Bone Disease 

    The Lancet Oncology September 2001 Vol. 2 (9) Pg. 573-575

          

    Symptoms related to skeletons are the most common problems in patients with multiple myeloma. Myeloma bone disease has various aspects. The osteolytic lesion (osteopenia) and pain, pathological fracture, and hypercalcaemia are related skeletal events.

           

    Myeloma cells induces osteoclast and thereby its stimulation produces resorption of bone and further osteoclast signal the myeloma cells to grow and behave aggressively. RANK.Fc is an inhibitor of osteoclast activity. RANK receptor is present on osteoclasts and receives the signals that stimulate osteoclast formation and activation. Many cytokines are indicated during this process.

         

    Bisphosphonates reduce the pain pathological fracture and episodes of hypercalcaemia and need for radiotherapy.

          

  • Brian Durie (Cedars-Sinai Comprehensive Cancer Center, Los Angeles, USA)

    International Myeloma Grand Round

    Thalidomide and Prognostic Factors in Myeloma 

    The Lancet Oncology September 2001 Vol. 2 (9) Pg. 575-577

          

    Younger patients at diagnosis have a better outlook as they tolerate the therapy (aggressive chemotherapy and high dose chemotherapy with transplantation) better. They also have a different biology of disease. Chromosome13 increase b2 microglobulin have poor prognosis.

           

    The promising new biological therapies include thalidomide and its analogues, IMID-501 and proteasome inhibitor (PS-341). Thalidomide has a mild antangiogenic effect and hence VIGF may also be effective. Apart from antangiogenesis other mechanism of action of thalidomide include alteration of T cell function or down regulation of adhesion molecule and
    microenvironment.

           

    Patient in whom lowest dose works have a propensity of prolonged remission duration thalidomide + dexamethasone induces 77% response in previously untreated patients of multiple
    myeloma.

          



 

 

Speciality Spotlight

 

 

Multiple Myeloma
   

  • Wheatley K, for the Myeloma Trialists’ Collaborative Group [ Radcliffe Infirmarry Oxford, England ]
    Combination Chemotherapy Versus Melphalan Plus Prednisone as Treatment for Multiple Myeloma : An Overview of 6633 Patients From 27 Randomized Trials
    J Clin Oncol 16: 3832-3842, 1998
      
    Standard induction chemotherapy for patients with multiple myeloma has been melphalan and prednisone [MP]. In an effort to improve the results of M&P many investigators have used aggressive combined chemotherapy [CCT].
      
    This overview of 4930 patients and an addition 1703 patients worldwide and from published studies were compared between M&P and CCT.
      
    The overview revealed no significant difference in survival rates associated with CCT and MP. Therefore MP remains the standard treatment for patients who are not candidates for high dose chemotherapy and autologous stem cell transplant. For transplant patients, the editor prefers vincristine, doxorubicin and dexamethasone as this combination provides rapid response and cause less toxicity to stem cells.
       

  • Singhal S, Mehta J, Desikan R, et al (Univ of South Carolina, Columbia; Univ of Arkansas, Little Rock; Rockefeller Univ, New York)
    Antitumor Activity of Thalidomide in Refractory Multiple Myeloma
    N Engl J Med 341: 1565-1571, 1999
      
    Refractory myelomas have limited therapeutic options. Bone marrow vascularization a hallmark of high plasma cell-labeling index and disease activity confers poor prognosis. Thalidomide has antiangiogenic activity. This study of 84 relapse myelomas most of whom had undergone high dose chemotherapy each one received thalidomide 200 mg/day and dose increased every 2 weeks up to 800 mg/day.
      
    The overall response rate defined as at least 25% reductions in paraprotein occurred in 32%.
      
    The common side effects included constipation, weakness or fatigue and somnolence.
       

  • Vescio R, Schiller G, Stewart AK, et al (Univ of California, Los Angeles; Toronto Hosp; Univ of South Florida, Miami; et al)
    Multicentre Phase III Trial to Evaluate CD34+ Selected Versus Unselected Autologous Peripheral Blood Progenitor Cell Transplantation in Multiple Myeloma
    Blood 93: 1858-1868, 1999
       
    Peripheral blood progenitor are the preferred source of autografts due to quicker restoration of hematopoiesis and procedure of harvesting is possible without general anesthesia.
      
    This study of 131 patients of multiple myeloma were randomized to CD34 selected or unselected autologous transplant myeloablative therapy.
      
    The CD34 selection could decrease 3.1 log in the number of contaminating tumor cells and there was no significant difference in platelet engraftment.
      
    Although this could not translate into an improvement in outcome or a decrease in relapse as most of the relapses are due to untreated endogenous tumor and not due to contamination of tumor cell.
           

  • Jean-Luc Harousseau (Service D’Hematologie Clinique, Nantes, France)
    International Myeloma Grand Round
    Current Status of High-Dose Chemotherapy

    The Lancet Oncology September 2001 Vol. 2 (9) Pg. 572-573
       
    The French cooperative group, have randomised patients of multiple myeloma to conventional chemotherapy followed by interferon, to conventional chemotherapy followed by high dose therapy (HDT) with 140 mg/m2 of melphalan plus total body irradiation (TBI) followed by autologous bone-marrow transplantation and interferon.
      
    The HDT group had 22% patient in CR and 16% have a very good partial remission compared with 14% in conventional arm survival is longer in those who achieve CR.
      
    A comparison of the French regimen of melphalan 140 mg/m2 plus TBI with that of Royal Marsden regimen melphalan 200 mg/m2 revealed higher toxic side effects with French regimens, 3.6% toxicity related death in radiotherapy group and overall survival was also better with Royal Marsden regimen which was due to better salvage therapy at the time of relapse.
       
    Barlogie and colleagues have revealed improved CR with repeated courses of melphalan and two autologous transplantation. The French study also inferred that in those patient it was feasible to do two transplants with blood, had better complete and very good partial remission.
      
    The prognostic factors identified in patients treated with HDT are detection of chromosome 13 by FISH and high b2-microglobulin levels.
       

  • Gregory R. Mundy (University of Texas Health Science Center, Texas, USA)
    International Myeloma Grand Round
    Investigation, Prophylaxis, and Treatment of Bone Disease 
    The Lancet Oncology September 2001 Vol. 2 (9) Pg. 573-575
          
    Symptoms related to skeletons are the most common problems in patients with multiple myeloma. Myeloma bone disease has various aspects. The osteolytic lesion (osteopenia) and pain, pathological fracture, and hypercalcaemia are related skeletal events.
           
    Myeloma cells induces osteoclast and thereby its stimulation produces resorption of bone and further osteoclast signal the myeloma cells to grow and behave aggressively. RANK.Fc is an inhibitor of osteoclast activity. RANK receptor is present on osteoclasts and receives the signals that stimulate osteoclast formation and activation. Many cytokines are indicated during this process.
         
    Bisphosphonates reduce the pain pathological fracture and episodes of hypercalcaemia and need for radiotherapy.
          

  • Brian Durie (Cedars-Sinai Comprehensive Cancer Center, Los Angeles, USA)
    International Myeloma Grand Round
    Thalidomide and Prognostic Factors in Myeloma 
    The Lancet Oncology September 2001 Vol. 2 (9) Pg. 575-577
          
    Younger patients at diagnosis have a better outlook as they tolerate the therapy (aggressive chemotherapy and high dose chemotherapy with transplantation) better. They also have a different biology of disease. Chromosome13 increase b2 microglobulin have poor prognosis.
           
    The promising new biological therapies include thalidomide and its analogues, IMID-501 and proteasome inhibitor (PS-341). Thalidomide has a mild antangiogenic effect and hence VIGF may also be effective. Apart from antangiogenesis other mechanism of action of thalidomide include alteration of T cell function or down regulation of adhesion molecule and microenvironment.
           
    Patient in whom lowest dose works have a propensity of prolonged remission duration thalidomide + dexamethasone induces 77% response in previously untreated patients of multiple myeloma.
          

 

By |2022-07-20T16:44:10+00:00July 20, 2022|Uncategorized|Comments Off on Multiple Myeloma

About the Author: