Pooled Analysis Shows Maintenance Therapy Improves Survival in Multiple Myeloma

Though previous studies have indicated prolonged progression-free survival (PFS) with maintenance therapy in patients with multiple myeloma (MM), experts disagree about its effect on overall survival (OS) and whether prolonged treatment after complete response is necessary. Chiara Cerrato, MD, from the University of Torino in Italy, and colleagues conducted a pooled analysis of five clinical trials to clarify the role of maintenance therapy in patients with a complete response to treatment. The results were presented at the 15th International Myeloma Workshop.

Dr. Cerrato and researchers analyzed patient data from five phase III trials: three including patients who were eligible for autologous hematopoietic stem cell transplantation (AHCT) and two including patients 65 years or older who were ineligible for AHCT (TABLE).

A total of 2,792 patients were analyzed: 2,330 patients (79%) received maintenance therapy; 503 (21%) of these patients had achieved a CR prior to maintenance therapy (378 of whom were transplant-eligible and 125 were transplant-ineligible). After a median follow-up of 47 months, the researchers identified a significant advantage in terms of five-year OS and PFS (the study’s primary endpoint) for patients who received maintenance therapy as part of the study protocol:

  • Five-year OS: 79% versus 59% (hazard ratio [HR]=0.5; p<0.0001)
  • Five-year PFS: 66% versus 20% (HR=0.3; p<0.001)

“The role of maintenance therapy in MM has been a subject of debate,” Dr. Cerrato noted during her presentation, “but our study finds it is really important to go on with treatment, with a difference in OS and PFS in all patients with drug-sensitive disease.”

In subgroup analyses by age (<65 vs. ≥65 years old) and type of treatment (AHCT vs. conventional chemotherapy), Dr. Cerrato and colleagues found that patients who continued treatment after achieving CR had longer PFS compared with those who did not receive maintenance therapy across all subgroups, including:

  • Patients who underwent AHCT (median PFS=86 months vs. 40 months; HR=0.3; p<0.0001)
  • Patients <65 years old receiving conventional chemotherapy (median PFS=not reached vs. 21 months; HR=0.2; p<0.0001)
  • Patients ≥65 years old receiving conventional chemotherapy (median PFS=52 months vs. 34 months; HR=0.5; p=0.003)

In terms of OS, the researchers observed an advantage in both young and older patients receiving conventional chemotherapy (HR=0.4 and 0.5; p=0.06 and p=0.02, respectively). However, there were no differences in OS among young patients undergoing AHCT (HR=1.3; p=0.8). In her presentation, Dr. Cerrato noted that longer-term follow-up will be needed to confirm whether maintenance therapy will improve OS in younger patients.

In addition, the pooled analysis did not include a crossover of patients from non-maintenance to maintenance regimens, making it difficult to interpret the difference in OS.

“Maintenance treatment prolongs PFS, regardless of age and type of treatment, in CR patients,” the authors concluded, “and maintenance is particularly beneficial in patients with sensitive disease.”


Reference

Cerrato C, Gay F, Petrucci MT, et al. Continuous treatment improves survival of newly diagnosed multiple myeloma patients achieving complete response: data from 5 phase III trials including young and elderly patients. Abstract BP-017. Presented at the 15th International Myeloma Workshop, September 23, 2015; Rome, Italy.

TABLE. Phase III Trials Included in the Pooled Analysis
Trial Induction Maintenance
Patients eligible for AHCT
RV-MM 209 Melphalan/prednisone/lenalidomide and melphalan 200 mg/m2 With or without lenalidomide
RV-MM-EMN-441 Carfilzomib/revlimid/dexamethasone and melphalan 200 mg/m2 Lenalidomide or lenalidomide/prednisone
HOVON-65/GMMG-HD4 Bortezomib/doxorubicin/dexamethasone Bortezomib or thalidomide
Vincristine/doxorubicin/dexamethasone
Patients ≥65 years ineligible for AHCT
GIMEMA-MM0305 Bortezomib/melphalan/prednisone/thalidomide Bortezomib/thalidomide
Bortezomib/melphalan/thalidomide No further therapy
EMN01 Lenalidomide/dexamethasone Lenalidomide vs. lenalidomide/prednisone
Cyclophosphamide/prednisone
Melphalan/prednisone

 

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