Second Autologous Stem Cell Transplant (ASCT) as Salvage Therapy in Patients with Relapsed Multiple Myeloma: Improved Outcomes in Patients with Longer Disease Free Interval after First ASCT.
Abstract Background: Single autologous stem cell transplant (ASCT) is considered the standard of care for younger multiple myeloma (MM) patients (pts). However, it is not curative and virtually all patients will ultimately relapse. As more options, such as biological therapy, are available to treat relapsed disease, the role of a second ASCT as salvage therapy is unclear. Method: Retrospective review of all MM pts who received a 2nd ASCT as salvage therapy at Princess Margaret Hospital. Results: Between February 1997 and June 2007, 61 MM pts received a second ASCT for relapsed MM at our institution. Median age was 56 yrs (range 35–71) at second transplant. 37 pts (61%) were male. Immunoglobulin subtype included IgG (36), IgA (14), light chain (6), nonsecretory (3), IgM(1) and IgD (1). Transplant conditioning regimen for first transplant was high dose melphalan (MEL) 140–200 mg/m2 in 51, MEL/etoposide(E)/TBI in 4, and MELl/TBI in 2. 2nd ASCT conditioning consisted of MEL + TBI +/− E in 2, MEL alone in 58 and Busulfan/Cyclophosphomide in 1. The median time from diagnosis to first transplant was 9.7 months (2.0–74.2). The median time to relapse after the first transplant was 32.6 months (9.7–85.6), with a median interval between transplants of 45.1 months (19.7– 115). Two transplant-related deaths occurred (3%). Response to first transplant was 4 CR (8%), 34 PR (68%), 2 MR (4%) and 10 SD (20%). Nineteen pts went on to maintenance therapy between transplants. Response to second transplant was 4 CR (8%), 41 PR (80%), 5 SD (10%) and 1 PD (2%). Median progression-free survival (PFS) was 15.8 months (0–63.8) while median overall survival (OS) was 4.2 years (0–7.0) after 2nd ASCT. The relationship between progression-free interval after 1st ASCT and the outcome of the 2nd ASCT is summarized Table 1. Patients can be stratified into two groups, those with a disease free interval of less than or greater than 24 months. The use of maintenance therapy did not differ between the two groups, 6 (40%) in patients with PFS ≤24 months and 13 (28%) in patients with PFS >24 months. Conclusions: 2nd ASCT is a feasible and safe salvage therapy in patients with relapsed MM. 2nd ASCT is effective in providing a median progression free survival of 1.25 years and median overall survival of 4.2 years after 2nd ASCT - results that compare favourably with other salvage approaches. Patients with a longer disease free interval after 1st ASCT experience a better progression free survival and overall survival after 2nd ASCT. It is reasonable, therefore, to consider a 2nd ASCT if the time to progression is greater than 2 years after first ASCT. Outcomes Based on Time to Progression Post 1st ASCT PFS post 1st ASCT # of pts median PFS post 2nd ASCT PFS post 2nd ASCT1 Median OS post 2nd ASCT OS post 2nd ASCT2 1 p< 0.005, 2 p< 0.05 ≤24 months 15 12.7 months 1 year: 46% 3.5 years 1 year: 85% 2 year: 11% 2 years: 76% 3 years 0% 3 years: 63% 4 years: 31% > 24 months 46 19.8 months 1 year: 74% 5.9 years 1 year: 91% 2 year: 45% 2 years: 82% 3 year: 31% 3 years: 65% 4 years: 55%
Second Autologous Stem Cell Transplant (ASCT) as Salvage Therapy in Patients with Relapsed Multiple Myeloma.
Abstract Abstract 1217 Poster Board I-239 Background Single autologous stem cell transplant (ASCT) is considered the standard of care after induction therapy for younger multiple myeloma (MM) patients (pts). However, it is not curative and virtually all patients will ultimately relapse. As more options are available to treat relapsed disease, the role of a second ASCT as salvage therapy is unclear. Method Retrospective review of all MM pts who received a 2nd ASCT as salvage therapy at Princess Margaret Hospital. Results Between February 1997 and July 2009, 79 MM pts received a second ASCT for relapsed MM at our institution. Median age was 60 yrs (range 39-72) at second transplant. 48 pts (61%) were male. Immunoglobulin subtype included IgG (42), IgA (21), light chain (11), nonsecretory (3), IgM(1) and IgD (1). Transplant conditioning regimen for first transplant was high dose melphalan (MEL) 140-200 mg/m2 in 67, busulphan and cyclophosphamide in 1, and combinations of MEL with etoposide (E) or TBI in the rest. 2nd ASCT conditioning consisted of MEL alone in 76, the remaining 3 had MEL with either TBI or E. The median time to relapse after the first transplant was 2.72 years (0.81-8.26), with a median interval between transplants of 3.61 years (1.63-9.59). Response to first transplant in 78 evaluable patients was 13 CR/nCR (17%), 56 PR/VGPR (72%), 9 MR/SD (12%). Nineteen pts received maintenance therapy between transplants. Two transplant-related deaths occurred following 2nd ASCT. In 73 evaluable patients, response to second transplant was 11 CR/nCR (15%), 57 PR (78%), 6 MR/SD (8%). After 2nd ASCT, with median follow up 5.92 years (71 months), median progression-free survival (PFS) was 18.5 months and median overall survival (OS) was 4.4 years. Long term progression-free status based on the progression-free interval after 1st ASCT is summarized Table 1. PFS based on progression free interval after 1st ASCT is outlined in Figure 1. Conclusions 2nd ASCT is a feasible and safe salvage therapy in relapsed MM patients. It is effective in providing a median progression free survival of 18.5 months and median overall survival of 4.4 years (52.8 months) after 2nd ASCT. This is comparable if not better than modern salvage chemotherapies. The longer the disease free interval after 1st ASCT the more effective 2nd ASCT is at extending both progression free survival and overall survival. It is reasonable, therefore, to consider a 2nd ASCT if the time to progression is greater than 2 years after first ASCT. Disclosures Chen: Celgene: Honoraria, Research Funding; Ortho Biotech: Honoraria. Trudel:Celgene: Honoraria, Speakers Bureau; Ortho Biotech: Honoraria. Kukreti:Celgene: Honoraria.