Novel Agents Versus Conventional Drugs for the Treatment of Relapsed Multiple Myeloma Patients: Experience of a Single Center over the Last 25 Years

Background: New active classes of drugs such as proteasome inhibitors (e.g., bortezomib) and immunomodulatory drugs-IMiDs (e.g., thalidomide and lenalidomide) are nowadays the standard treatment for multiple myeloma (MM) patients, alone or in association with old agents. The achievement of deeper responses, using novel agents instead of conventional treatment, is a significant prognostic factor for the outcome of these patients, resulting in an improved overall survival (OS) and progression-free survival (PFS). Here, we report the single center real life comparison between the outcome achieved with old agents with that obtained with novel agents in young MM patients treated at first relapse over a 25-year period.

Patients and Methods: We analyzed a cohort of 258 young (median age 55 years; range 19-69) newly diagnosed MM patients treated at our Center between August 1989 and November 2014. All patients received old or novel agents followed by autologous hematopoietic stem cell transplantation (single or tandem) as first line treatment. Of the 258 patients, 144 experienced a progression of disease after a median of 34 months (range 7-195) and received old or novel agents as second line therapy. Old agents used as first and second line treatment were prevalently vincristine, doxorubicin and dexamethasone (VAD), melphalan and prednisone (MP) or cyclophosphamide and dexamethasone (CD); novel agents included velcade-based or IMiD-based regimens. Our cohort was divided into four different groups: 1) 51 patients treated with old agents as first and second line therapy (35.4%);2) 79 patients treated with old agents as first line therapy and novel agents as second line therapy (54.8%);3) 2 patients treated with novel agents in induction therapy and subsequently with old agents as second line therapy (1.4%);4) 12 patients treated with novel agents both in first and second line (8.3%). Our analysis focused on groups 1 and 2; group 3 was not considered for the small number of patients and because the choice of treatment was based exclusively on a worsening of the clinical condition; group 4 was not included for the small number of patients and because of the short follow-up. Our aim was to compare the results obtained in patients treated only with old agents both as first and second line treatment with the outcome of patients who received old agents as first treatment and novel agents as second line treatment, to assess the impact of novel agents in real life MM patients' management.

Results: The OS at 5 years for patients of group 2 was significantly higher than that of group 1 patients (41.6% vs 14.1%); even at 10 years, the OS was significantly better for group 2 (20.4% vs 2.4%, p<0.0001); median OS was 4.1 years for group 2 and 1.4 years for group 1. The PFS was superior for patients treated with novel agents as second line treatment both at 5 years (12% vs 6.9%) and at 10 years (10% vs 2.3%) (p=0.02); median PFS was 1.4 years for group 2 and 0.7 for group 1. PFS2, considered as the interval from the start of first line treatment to the date of second relapse, showed also significantly better results for group 2 patients compared to group 1 patients both at 5 (61.8% vs 33.3%) and 10 years (25.7% vs 9.2%). Median PFS2 was 6.8 years for group 2 and 3.7 years for group 1(p=0.0002).

Conclusions: We analyzed the effect of the introduction of novel agents in a cohort of young MM patients treated at our Center over a 25-year period, between 1989 and 2014. Patients treated in the earlier years received old agents both as first and second line treatment, while in more recent years all patients who experienced a relapse were treated with novel agents as second line treatment. Our analysis underlines that patients receiving novel agents witnessed a significantly better OS and PFS compared to patients treated only with old agents. When focusing on PFS2, we could determine that the duration of response obtained with proteasome inhibitors and IMiDs was significantly longer than that obtained with conventional chemotherapy. This currently ongoing study and a longer follow-up in a larger number of group 4 patients will allow to conclusively define the true real life impact of novel agents when used both as first and second line treatment for the management of young MM patients.