Authors: Alvarado Ibarra Martha, Mujica Martínez Aldo, Pérez Zuñiga Juan Manuel, Hernández Ruiz Eleazar, Paredes Lozano Eugenia Patricia, Trejo Gómora Jorge, Ron Guerrero Carlos, Alvarez Vera José Luis, Ortiz Zepeda Maricela, Mena Zepeda Veronica, De la Peña Celaya Antonio, Espitia Rios Eugenia, Ramí
Background: Chemotherapy with multiple drugs has been a crucial step in the treatment of Multiple Myeloma producing a high deep response rate and improving progression-free survival and overall survival. The efficacy of bortezomib in the induction of remission has been demonstrated in different studies. Cytotoxic drugs such as Doxorubicin, Cyclophosphamide or Thalidomide have been combined with Bortezomib / Dexamethasone. There are few randomized studies comparing remission with Bortezomib / Dexamethasone with Cyclophosphamide, Doxorubicin or Thalidomide inductions treatments.
Primary Endpoints: Primary Endpoints were to compare Overall Survival (OS), Progression-Free Survival (PFS) and Response Rates. As Secondary Endpoints, to determine the factors that correlate with PFS and to know the incidence of adverse events.
Patients and Methods: A prospective, multicenter, comparative cohort study including patients diagnosed with multiple myeloma who received Bortezomib-Dexamethasone plus Cyclophosphamide (BORCIC) or Doxorubicin (BORDOX) or Thalidomide (BORTAL) as the first-line chemotherapy. Evaluated and compared data were: response, progression-free survival, overall survival and toxicity.
Results: A total of 201 patients were studied from 2010 to 2015, 88 women (44%), 113 men (56%). The characteristics of the disease were similar for each treatment group. Distribution of monoclonal component type was 20% IgA (40), 62% IgG (125), nonsecretory and light chains 18% (36). Durie-Salmon Staging was: I 17% (35), II 33% (67), III 50% (99). Staging by International Staging System (ISS) was I: 18% (n = 37), II: 44% (n = 90) and III 38% (n = 74). 40% (80) of patients started with a fracture at the time of diagnosis. Renal failure was present in 20% (40) of the patients at diagnosis. The overall response: Group (BORCIC) CR/VGPR (n= 60) was 87%; Group (BORDOX) CR/VGPR (n=44) was 69% and in Group (BORTAL) CR/VGPR was 91% (n=63); p 0.006. Progression was greater in group (BORDOX, n = 36), compared with group (BORCIC, n = 27) and group (BORTAL, n = 23) (p 0.04). Median progression-free survival for group (BORTAL) was 36 months, for group (BORCIC) was 28 months and for group (BORDOX) was 20 months (p 0.006). Median OS for those with CR was not reached, for those with VGPR was 27 months and for those with PR was 17 months (p 0.0001). The overall incidence of neuropathy was BORCIC n=46, BORDOX n = 39, BORTAL n = 47, (p 0.77).
Conclusion: In our experience, the best first-line treatment regimens for patients with multiple myeloma are those that include Bortezomib, Dexamethasone with Thalidomide or Cyclophosphamide, with no difference in response rate and response type, overall survival and progression-free survival. These regimens showed similar toxicity rates. The regimen that includes Doxorubicin is the regimen with the worst results for both progression-free survival, overall survival and toxicity, so we do not suggest it as a first-line treatment regimen.View/Download pdf