Impact of Response to Thalidomide, Lenalidomide or Bortezomib Containing Induction Chemotherapy on Outcomes of Multiple Myeloma Patients Undergoing Autologous Transplantation – A Multicenter Analysis

High dose therapy and autologous transplantation (HDT-AT) has shown survival benefit for (at least) young, transplant eligible multiple myeloma (MM) patients. Transplant ineligible patients who achieve complete remission (CR) with novel chemotherapy agents, have recently been shown to have superior overall survival (OS) (Harousseau JL. Blood:2010). However transplant eligible MM patients who have refractory disease in response to induction chemotherapy (not containing novel agents) before HDT-AT do not have inferior outcomes post-transplantation. A recent single institution, retrospective study has shown that <50% reduction in ‘serum M-protein’ following induction with thalidomide (T) or lenalidomide (L)-based induction therapies, predicts poor outcomes following HDT-AT (Gertz M, Blood:2010). These findings require further validation in order to refine patient selection for HDT-AT. We report here the impact pre-transplant remission status on outcomes of HDT-AT in MM patients receiving induction chemotherapy with novel agents.

This multicenter outcomes study includes 121 consecutive patients who underwent a planned, single autograft within 1-year of starting induction chemotherapy with regimens containing T, L, or bortezomib (B), from 2003–2009. Peripheral blood stem cells were mobilized using a cyclophosphamide/G-CSF combination. All patients with normal renal function received uniform conditioning with Mel200 (MEL140 if serum creatinine was >2 mg/dl). The disease response pre- and post transplant was determined by using the IMWG criteria. SPSS version 13.0 was used for statistical analysis. Kaplan-Meier method was used to calculate OS and progression free survival (PFS). In order to assess the impact of chemosensitive disease, outcomes of patients achieving at least a partial remission (PR) (≥PR-group; n=105) before HDT-AT were compared with one not achieving at least a PR (<PR-group; n=16). We also compared outcomes of patient achieving at least a very good partial response (VGPR) (≥VGPR-group; n=48) with ones not achieving at least a VGPR (<VGPR-group; n=73).

The median age of the patients at transplant was 57yrs (range 35 –76yrs). Eighty (65%) patients were male. At diagnosis 84 (68%) had Salmon-Durie stage III disease, while 37 (31%) had stage I/II disease. At transplantation median Karnofsky performance status was 90, median number of prior therapies was 1 (range 1–4), and 31 (25%) had received radiation previously. Median follow-up of surviving patients is 24 months. KM estimates of 3 year OS of patients in ≥PR-group and <PR-group was 74% vs. 77% (p=0.94) respectively. The 3 year PFS in similar order was 44.8% vs. 45% (p=0.87). The 3 year OS of patients in ≥VGPR-group and <VGPR-group (73% vs. 75%) was also not significantly different (p=0.83). Respective figures of 3 year PFS are 54% vs. 38% (p=0.97) respectively. Of the 53 patients that entered an HDT-AT with a PR, 23 improved to a CR post transplant, 2 improved their status to a VGPR whereas 28 remained in a PR. On the other hand of the 8 patients who entered an HDT-AT with a VGPR, 2 improved to a CR whereas the rest maintained their status.

Our limited, multicenter retrospective outcomes data suggest that response to induction chemotherapy with novel agents may not reliably predict outcome of MM patients undergoing HDT-AT. Until data from prospective studies prove otherwise, MM patients who are refractory to therapy with T/L or B-based agents should not routinely be considered ineligible for HDT-AT.

Abraham:Genentech: Membership on an entity's Board of Directors or advisory committees. Craig:Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hamadani:celgene: Honoraria, Speakers Bureau; otsuka: Research Funding, Speakers Bureau.