High Dose Therapy and Autologous Stem Cell Transplantation Results in Good Outcomes and Acceptable Toxicities in Elderly Patients with Non-Hodgkin's Lymphoma

s / Biol Blood Marrow Transplant 19 (2013) S129eS149 S133 Achievement of a complete remission (CR) is considered an important goal of therapy in multiple myeloma (MM). High dose chemotherapy with autologous stem cell transplantation (ASCT) was the first treatment to reliably produce CR in MM. Several approaches have been tried to further increase the CR rate including polychemotherapy preparative regimens, tandem ASCT, consolidation and/or maintenance therapy. Since there is a dose response effect for melphalan, we evaluated an alternative single ASCT strategy using higher dose melphalan at 280 mg/m2 (MEL 280). Methods: We completed a multicenter, phase II trial of MEL 280 in patients withMMundergoing ASCTafter a median of 1 prior regimen. Twodoses of amifostine (AF) 740mg/m2 IVover 5-15 minutes were administered 24 hour and 15 min before MEL 280 to ameliorate mucosal toxicity. Between 5/1999 and 10/2003, 58MMpatients (pts) received this highdose regimen after dexamethasone-based induction regimens. Lenalidomide or bortezomib were not used in induction. Themedian agewas 50 yrs (35-66), 33weremale, median initial beta 2-microglobulin level was 3.0 mg/L (0.8-22.4). The subtypes included IgG (n1⁄4 32), IgA (n 1⁄415), light chain (n 1⁄4 8)and non-secretory (n1⁄4 3); 67% had Durie Salmon stage III disease; 90% of pts were chemosensitive to dexamethasone-based induction therapy. Median time from diagnosis to ASCT was 7.5 months. Toxicity: Bearman critieria were utilized for grading regimen-related toxicity (RRT): grade 1 mucositis was seen in 41%, grade 2 in 14% and grade 3 in 1.7%. Other grade 3 toxicities included: lung (1.7%) and renal (1.7%); 1 pt died from melphalan-induced interstitial pneumonitis; 7% experienced atrial fibrillation or flutter. Of the 57 evaluable pts, CR was achieved in 28 (49%), VGPR in 6 (11%), PR in 17 (30%), SD in 4 (7%) unknown in 1 (1.5%) and progression in 1 (1.5%). At a median follow-up of 7 yrs, 76% of pts have progressed and 57% have died. The cause of deathwasMM in 88% (29/33) and non-relapse causes in 4 (1 lung cancer,1 coronary disease, 1 sepsis and 1 complications of subsequent allogeneic transplant). The median overall survival (OS) is 67 months while the median progression-free survival (PFS) is 22 months. PFS and OS at 7 years was 10% and 39% respectively. Conclusions: MEL 280 + AF is well-tolerated with low transplant related mortality. Excellent VGPR+CR rates of 60% were achieved in the pre-novel agent era. However, the high CR + VGPR rate after ASCT did not translate into an improvement in PFS/OS from single or tandem ASCT trials in that era (Barlogie et al. J Clin Oncol. 2010; 28: 1209-14). In contrast to recent studies showing CR correlates with improved long term outcomes, MEL 280 dose escalation increased response depth, however, sustainability of response is not impacted. 43 High Dose Therapy and Autologous Stem Cell Transplantation Results in Good Outcomes and Acceptable Toxicities in Elderly Patients with Non-Hodgkin's Lymphoma Roni Tamari , Parastoo Dahi , Sean Devlin , Jenna Goldberg , Paul Hamlin Paul , Matthew Matasar , Jocelyn Maragulia , Miguel-Angel Perales , Craig H. Moskowitz , Craig Steven Sauter . 1 Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan-Kettering Cancer Center, New York, NY; 2 equal authorship; 3 Department of Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY; 4 Division of Hematologic Oncology, Memorial Sloan Kettering Cancer Center, New York City, NY; Memorial Sloan-Kettering Cancer Center; 6 Division of Hematologic Oncology, Memorial Sloan-Kettering Cancer Center, New York City, NY Background: High-dose therapy and autologous stem-cell transplantation (HDT-ASCT) can offer potential long-term remission or cure in patients with high risk non-Hodgkin's lymphoma (NHL). Limited experience is available on the safety and efficacy of HDT-ASCT in elderly patients. Methods: This is a single-center, retrospective study examining outcomes of HDT-ASCT for NHL in 145 patients 60 years and older between January 2001 and December 2010. Clinical data and comorbidities were correlated with outcomes. Overall survival (OS) and progression-free survival (PFS) were analyzed according to age at transplant, histology, hematopoietic cell transplantation comorbidity index (HCTCI) and first remission versus subsequent remission at the time of HDT-ASCT. Results: The median age was 65 (range 60-74). Fifty-nine, 67 and 20 patients were ages 60 70, respectively. Patients underwent HDT-ASCT for diffuse large B-cell lymphoma (DLBCL, n1⁄457, 39%), mantle cell lymphoma (MCL, n1⁄453, 37%) and other NHL subtypes (n1⁄435, 24%). HDT-ASCT in first remission was performed in 68 patients (47%), mostly with MCL (70%). BEAM and RRBEAM were the most common conditioning regimens (85%). 34 (23%), 35 (24%) and 77 (53%) patients had a low (0), intermediate (1-2) and high (>3) HCT-CI score at transplant. Overall, with a median follow-up of 3.2 years (range 0.2-8.1) for survivors, PFS and OS at 2 years were 71% and 76%, respectively. Age and HCT-CI score did not affect OS or PFS. Patients with MCL had better outcomes compared to other NHL histologies with 2 years OS of 90% versus 65% and PFS of 85% versus 58% respectively. The one year incidence of progression was 4% in MCL, 28% in DLBCL and 34% for other NHL histologies. A total of 54 patients (37%) progressed [24 (44%) DLBCL, 14 (26%) MCL and 16 (30%) others]. Median time to treatment failure was 11.6 months (range 1.3-88). Three (2%) patients died from transplant complications. High-risk status by HCT-CI was not associated with TRM. Six patients (4%) developed secondary myelodysplastic syndrome (MDS) at a median of 40 months (range 5-83). Conclusion: In this large cohort of elderly patients with NHL who underwent HDT-ASCT, we demonstrate that this intervention is feasible, tolerable, and effective, and results in similar disease control and survival as in younger historical controls. Our data suggest that age alone is not predictive of post transplant outcomes and therefore should not be used to preclude HDT-ASCT in elderly.