First line therapy for patients with newly diagnosed multiple myeloma ineligible for autologous stem cell transplantation: a systematic review and meta-analysis (hemo-oncolgroup study)

ABSTRACT

Background: Patients not eligible for stem cell transplantation (SCT) have been treated with melphalan (M) plus prednisone (P); however, the standard of care has shifted to MP plus thalidomide(T) due to a greater survival benefit. Bortezomib (B) and lenalidomide have also emerged as effective agents. Methods: Randomized clinical trials (RCTs) that compared MP to any otherregimen were identified from the databases of Cochrane Library, PubMed, LILACS, EMBASE and Scirus. Results: Twenty-two trials were included from 2159 potential eligible references. MP vs.M plus dexamethasone (MD) (3 RCTs) MD was superior in partial response (PR) rate and non-hematological toxicity. MP vs. T-based regimens (4 RCTs) significant differences favoring T-basedregimens in complete response (CR) rate, partial response (PR) rate, and progression-free survival (PFS). MP vs. B based regimens (1 RCT) significant differences in overall survival (OS) , time to progression (TTP), CR and PR rate favored B-based regimens according to the European Group for Blood and Marrow Transplantation (EBMT) criteria. MP vs. chemotherapy regimens withoutM (3 RCTs) A significantly higher number of patients treated with BP achieved a CR. TTP was alsosignificantly longer in BP-treated patients (p < 0.02). MP vs. other polychemotherapy regimens(13 RCTs) No significant differences in PR, OS, hematological or other type of toxicity were observed between MP and the other chemotherapy regimens. Conclusions: Symptomatic multiplemyeloma patients ineligible for SCT should receive as first-line treatment a combination of MP plus B or T; these regimens are associated with improved outcome but greater toxicity comparedto MP alone. More homogeneous clinical trials using a cytogenetic risk approach are required