Lack of Prognostic Implications of Induction Response to Total Therapy 2 (TT-2) in Newly Diagnosed Patients with Multiple Myeloma (MM) for Post-Transplant Even-Free Survival (EFS) and Overall Survival (OS).

Abstract

Between October 1998 and February 2004, a total of 668 recently diagnosed myeloma patients were enrolled in TT-2, of whom 566 completed the first and 417 the second autotransplant. Twenty percent of patients were ≥ 65 years of age and 34% had abnormal metaphase cytogenetics; 24% had received a single cycle of chemotherapy prior to enrollment and 32% had a B2 microglobulin level of ≥ 4mg/L. All patients who completed at least the first transplant could be assessed for response to induction therapy consisting of VAD, DCEP, CAD and DCEP given with hematologic growth factor support at 4 to 5 week intervals. We examined whether the quality of induction response had an impact on event-free (EFS) and overall survival (OS). Responses were defined as complete remission (CR) if serum and urine immunofixation were negative with normal bone marrow plasmacytosis in aspirate and biopsy; partial remission (PR) if serum M protein was reduced by ≥ 75% and urine M-protein ≥ 90% with a normal bone marrow plasmacytosis and < PR for all other responses. Superior EFS (p=.04) and OS (p=.06) from first transplant were observed among the 86 CR patients (15%) with a 4-year estimate of EFS of 69% and OS of 83%, compared with 59% and 72%, respectively, for PR patients (N=214) and 52% and 68%, respectively, for < PR patients (N=266) (Figure 1 and 2). With a median follow-up of 3 years from the first transplant, we conclude that, although a stringently-defined CR after induction therapy resulted in a better EFS and OS, there was no difference in outcome between PR and < PR patients, who had virtually super imposable survival curves. These data, as well as a review of the literature (Vesole et al. Blood1994; 84: 950, Alexanian et al. Blood1994, 84: 4278 and Singhal et al. Bone Marrow Transplant2002, 30: 673) provide a strong argument for change in current Medicare policy, which denies autotransplants to myeloma patients who have failed primary induction therapy. Even with intensive induction therapy as applied in TT-2, more than two-thirds of patients achieving < PR prior to the first transplant are projected to be alive at 4 years after their autotransplant. Figure Figure Figure Figure