A Comparative Study of the Outcome of High-Dose Therapy and Autologous Hematopoietic Stem Cell Transplantation in Patients with High-Risk or Standard-Risk Myeloma Treated Concurrently,

Abstract

Abstract 4156▪▪This icon denotes a clinically relevant abstract Background:Chromosomal abnormalities detected either by conventional cytogenetics (CC) or interphase fluorescence in situ hybridization (FISH) have emerged as important prognostic markers in patients with multiple myeloma (MM) and are used to stratify patients into standard-risk (SR) or high-risk (HR) disease. HR myeloma is associated with shorter remission and survival even with novel agents and autologous hematopoietic stem cell transplantation (auto-HCT). In this report, we describe the outcome of patients with myeloma who received auto-HCT at our institution between January 2008 and December 2009, and had CC and FISH analyses available before auto-HCT to identify HR or SR disease. Methods:Primary objective was to compare the response rate, transplant-related mortality (TRM), time to progression (TTP), progression-free survival (PFS) and overall survival (OS) between HR and SR myeloma. HR myeloma was defined as having deletion of chromosomal 13 or 13q, t(4;14), and del17p by CC; or detection of t(4;14), t(14;16), or del17p by FISH in the bone marrow plasma cells (Munshi, N et al. Blood 2011 117: 4696–4700). Normal or any other CC or FISH abnormalities were considered SR. Response was assessed according to international uniform response criteria for myeloma (BGM Durie et al. Leukemia 2006 20(10):1–7). Kaplan & Meier curves were generated to calculate progression free survival (PFS) and overall survival (OS). Results:Between Jan 2008- Dec 2009, we identified 205 patients, who received auto-HCT at our institution and had pre-transplant CC and FISH analyses available. Twenty-eight patients (14%) had HR while 177 (86%) had SR myeloma. Table 1 summarizes patient characteristics and outcomes for HR and SR patients. Nine HR (30%) and 29 (16%) SR patients had international staging system (ISS) stage III at diagnosis (p=0.04). Twenty-one HR patients (70%) and 91 SR patients (51%) received induction therapy with a bortezomib-based regimen (p=0.01). Thirteen (46%) HR patients and 62 (35%) SR patients received post auto-HCT maintenance therapy (p=0.24). Nineteen HR patients (69%) and 165 SR patients (92%) achieved a CR, VGPR or PR after auto-HCT (p=0.00001). The median follow up in HR and SR patients was 14.5 months (2–30) and 12 months (1–35), respectively. Twenty-two (79%) HR and 46 (25%) SR patients had progressed at last follow up (p=0.00001). Similarly, 12 (43%) HR and 12 (7%) SR patients had died at last follow up (p<0.0001). Median PFS was 9.1 months in HR while it was 30.8 months in SR patients (p=0.000001). Median OS in HR was 19 months while median OS has not yet been reached in SR patients (p=0.000001). In HR patients only the use of maintenance therapy post auto-HCT significantly improved PFS and OS (p=0.001 and p=0.0007, respectively).Table 1:Patient Characteristics and OutcomeHigh-Risk Myeloma (N=28)Standard-Risk Myeloma (N=177)Age at transplant (years)56.5 (40–73)59 (35–78)GenderMale15 (54%)103 (58%)Female13 (46%)74 (42%)RaceWhite19 (68%)110 (62%)African American7 (25%)28 (16%)Asian05 (3%)Other2 (7%)34 (19%)Disease StatusFirst remission17 (60%)147 (83%)Relapsed11 (40%)30 (17%)Calcium mg/dl9.3 (7.7–10.2)8.9 (7.6–11.5)Creatinine mg/dl0.8 (0.5–1.7)0.8 (0.5–0.9)Hemoglobin g/dl9.8 (7.6–13.9)10.5 (6.8–16.5)International Staging System at diagnosisI6 (22%)52 (29%)II4 (14%)43 (25%)III9 (32%)29 (16%)unknown9 (32%)53 (30%)High-Risk chromosomal abnormalitiesDel17p15/28 (54%)Not ApplicableDel 13q18/28 (64%)t(4;14)3/28 (11%)t(14;16)1/28 (3%)Interval between diagnosis and auto-HCT9.4 (4–53)8.5 (2–266)Bortezomib® based Induction regimen21 (75%)91 (51%)Conditioning regimen Melphalan25 (89%)168 (95%)Maintenance therapy13 (46%) (9 Lenalidomide)62 (35%) (54 Lenalidomide)ResponsesCR022 (12%)CR2 (7%)25 (14%)VGPR13 (46%)76 (42%)PR4 (14%)42 (24%)SD3 (11%)11 (7%)PD6 (22%)1 (1%)Follow up in months (median)14.5 (2–30)12 (0–35)Progressed22 (79%)46 (25%)Progression Free Survival (median)9.1 months30.8 monthsMortality12 (43%)12 (7%)Overall survival (median)19.6 monthsNot reached Conclusion:Patients with HR myeloma had significantly worse outcome than patients with SR disease, even with novel agents and auto-HCT. In HR patients, maintenance therapy was associated with longer PFS and OS. Disclosures:No relevant conflicts of interest to declare.