Changing the Treatment Landscape of multiple myeloma (2003–2013). Own results

Новосад О.И., Крячок И.А., Ульянченко Е.О., Скрипец Т.В., Кадникова Т.В.

Summary. Introduction. The treatment options and outcomes for multiple myeloma (MM) patients were greatly changed over the last 10 years. Selecting treatment for patients according different age groups requires careful consideration of the balance between maximizing efficacy and ensuring acceptable tolerability. Objectives. The primary endpoint was to analyze and compare event-free (EFS) and overall survival (OS) in newly diagnosed MM patients who received chemotherapy or therapy with IMIDs or proteasome inhibitors. Materials and methods. The data of 100 newly diagnosed patients (median age: 63, range 34–80 years; males: 63, females: 37) who were treated at National Cancer Institute from Jan 2006 to Jan 2018 were analyzed. 19% (19/100) of patients were treated with M2, MP, DAV regimen (group 1), 46% (46/100) with thalidomide-based regimen (group 2) and 35% (35/100) — with proteasome inhibitor-based regimen (group 3). Chromosomal abnormalities [t(4:14), del13, and del17p13] were assessed in 28% patients. PFS and OS were analyzed depend on type of treatment regimen, 2- or 3-components in the treatment regimen, age and chromosomal abnormalities. Results. For 100 patients with MM the overall response rate (ORR) after the 1st line therapy was 70% (CR, VGPR, PR). 39% relapses during the follow-up period in patients after the 1 line therapy (median duration — 10.9 months; range 2–129 months) were recorded: 61.1% vs 47.8% vs 17.1% cases of relapse were diagnosed in group 1 vs group 2 vs group 3, respectively (p<0.05). 3-year EFS for group 1 was 18% vs 30% in group 3 and 20% vs 30% for group 2 vs group 3, respectively (p=0.002 by Cox-test). ROC-analysis confirmed that using of bortezomib-based regimen improve EFS in MM patients without any correlation with age (Se=81%; Sp=54%; AUC=0.7, p=0.0001). EFS was higher in patients younger than 65 years old in comparison with older patients in the group 2 (40% vs 18%, p<0.05). 3-year OS was 65% vs 45% in younger pts vs elderly pts, respectively (<65 y.o. vs > 65 y.o., logrank test, p=0.009). 3-year EFS and OS were similar in the group 3 pts who were <65 and >65 y.o. (logrank test, p=0.4). High level of adverse events, such as thrombosis in group 2 was registered in pts >65 y.o. (20%) vs <65 y.o. (7.7%), (p<0.05). We analyzed that the level of neurotoxicity in the three study groups was a similar (58.6% vs 60% vs 63%). Neurotoxicity complications were similar in different age groups also (58.6% vs 60%). 50% vs 33.8% cases of progression disease were detected in patients who received doublet and triplet regimens, respectively (p<0.05). ROC-analysis confirmed that doublet regimen is associated with more low EFS in elderly (>65 y.o.) MM patients (Se=50%; Sp=100%; AUC=0.7, p=0.04). Patients with del17p13 tended to have a higher rate of relapses, comparing to those who did not have it (p=0.09 by Cox-test). Median EFS in pts with del17p13 presence was lower without any correlation with age (10.9 vs 29.7 months). We did not find any significant association between patients with del13 or t(4:14) and clinical outcome of MM. Conclusions. Bortezomib-based regimens are still in a priority for the first-line treatment in different age groups. Thalidomide might be as an option for younger pts, because thrombosis events are more frequent in elderly pts. To achieve better response in the 1 line therapy it is preferably to use triplet regimens in pts <65 and >65 years old.
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