Bolejack, Vanessa

359 Background: GA, FOLFIRINOX and FOLFIRI are standard chemotherapy (CTX) regimens for mPC.The optimal introduction of these regimens following GA is not known. This phase II study evaluated 2 different approaches to this question. Methods: Eligibility criteria included 1) untreated mPC, 2) ECOG PS 0/1, 3) organ function adequate for Rx. Patients (pts) were treated according to one of 2 methods following GA given per standard dose/schedule: FOLFIRINOX (bolus 5-FU omitted) for up to 12 cycles at 24 weeks or at time of disease progression (S); or GA alternating with FOLFIRI q8 weeks up to 48 weeks total Rx (A). Results: 54 evaluable pts (28S, 26A) were enrolled . Pt characteristics included median age 65, M/F 48/52% , liver involvement 89%. 17/53 pts (31%) did not achieve disease control at 8 weeks (8 toxicity/complications , 6 disease progression, 3 declined further protocol therapy). Of the remaining 37 pts, 24/13 were treated with S/A regimens, respectively. Grade ≥ 3 treatment toxicities reported while on study with frequency ≥ 10% included anemia 21%, neutropenia 43%, thrombocytopenia 15%, and fatigue 22%. Grade ≥ 3 neuropathy occurred in 8% of pts. For all 54 pts using RECIST 1.0, CR/PR/SD/DC was 2 (4%)/20 (37%)/19 (35%)/41(76%). Ca19.9 response ≥ 90% was seen in 20/37 (54%). For all pts, median OS was 12.3 months ( 95% CI 8.6-14.5 mo); 12 and 24 mo OS was 51% and 11%, respectively. For the 37 pts with DC on GA at 8 weeks (calculated from start Rx) median OS was 13.5 mo (95% CI 10.7-15.4 mo); 12 and 24 mo OS was 55% and 16% , respectively. No statistically significant differences were seen between S and A with respect to toxicity, response or survival. Conclusions: 1) As opposed to introduction of 5FU-based CTX at the time of disease progression/prohibitive toxicity, introduction prior to that time may be at least comparable regarding both toxicity and OS. 2) This approach may further enhance OS in pts who achieve DC on GA at 8 weeks. 3) Neither S nor A method of 5FU-based CTX introduction following GA was clearly superior in this study. 4) How best to combine 5FU-based combination CTX following GA in mPC merits further study. Supported by the Seena Magowitz Foundation.

Purpose To assess the impact of age on outcome and to analyze the projected years of life lost in patients with multiple myeloma. Patients and Methods Ten thousand five hundred forty-nine patients were evaluated; 6,996 patients were treated with conventional chemotherapy, and 3,553 patients were treated with high-dose therapy with autologous stem-cell transplantation. Results Mean observed and relative overall survival times in the entire cohort were 3.7 and 3.9 years, respectively. Observed survival decreased steadily from 6.4 years in patients younger than age 50 years to 2.5 years in patients ≥ age 80 years. A similar decrease was noted for relative survival. Higher age correlated significantly with higher International Staging System (ISS) stage. Relative excess risk of death differed significantly between 10-year age cohorts beginning from age 40 years (P < .001 for age 50 to 59 v age 40 to 49, P < .001 for age 60 to 69 v age 50 to 59, P < .001 for age 70 to 79 v age 60 to 69, and P = .009 for age ≥ 80 v 70 to 79). The average years of life lost per patient was 16.8 years in the entire patient cohort and decreased steadily from 36.1 years in patients younger than 40 years old to 4.6 years in patients ≥ age 80 years. Conclusion Age is associated with higher ISS stage and is an important risk factor for early mortality. Survival declined continuously by each decade from age 50 to age ≥ 80 from more than 6 to less than 3 years. The average of years of life lost in patients with myeloma is higher than in many other cancers and amounts to more than 30 years in patients younger than 40 years old but decreases to less than 5 years in patients age 80 years or older.

AbstractWe analyzed the presenting features and survival in 1689 patients with multiple myeloma aged younger than 50 years compared with 8860 patients 50 years of age and older. Of the total 10 549 patients, 7765 received conventional therapy and 2784 received high-dose therapy. Young patients were more frequently male, had more favorable features such as low International Staging System (ISS) and Durie-Salmon stage as well as less frequently adverse prognostic factors including high C-reactive protein (CRP), low hemoglobin, increased serum creatinine, and poor performance status. Survival was significantly longer in young patients (median, 5.2 years vs 3.7 years; P < .001) both after conventional (median, 4.5 years vs 3.3 years; P < .001) or high-dose therapy (median, 7.5 years vs 5.7 years; P = .04). The 10-year survival rate was 19% after conventional therapy and 43% after high-dose therapy in young patients, and 8% and 29%, respectively, in older patients. Multivariate analysis revealed age as an independent risk factor during conventional therapy, but not after autologous transplantation. A total of 5 of the 10 independent risk factors identified for conventional therapy were also relevant for autologous transplantation. After adjusting for normal mortality, lower ISS stage and other favorable prognostic features seem to account for the significantly longer survival of young patients with multiple myeloma with age remaining a risk factor during conventional therapy.