Katz, Michael

Abstract Background: Immunomodulatory agents and proteasome inhibitors have significantly improved outcomes in the management of patients with multiple myeloma (MM). As a consequence, the role of upfront autologous stem cell transplant (ASCT) has become more controversial. The ECOG-ACRIN Cancer Research Group trial E4A03 demonstrated the superiority of lenalidomide (LEN) and low-dose dexamethasone (DEX; Ld) over LEN and high dose DEX (LD) in newly diagnosed MM (Rajkumar SV, Lancet Oncol, 2010). This led to the universal acceptance of Ld as a standard induction regimen. More recently, the FIRST study demonstrated the superiority of Ld as continuous therapy vs Ld given x 18 cycles and melphalan-thalidomide-prednisone x 12 cycles proving continuous Ld should be considered standard of care (Benboubker L, NEJM, 2014). Upon completion of four cycles of therapy, patients enrolled in E4A03 had the option of proceeding to ASCT or continuing on their assigned Ld or LD. A prior post-hoc retrospective landmark analysis (Siegel DS, Abstract, Blood 2010) comparing outcomes of early ASCT vs. no early ASCT showed that in patients <65, 65-70, and >70, the survival with early ASCT at 3 years appeared higher, supporting the role of early consolidative ASCT in newly diagnosed patients. This analysis is the long-term follow-up of the aforementioned study. Methods: A post hoc, retrospective landmark analysis was performed evaluating overall survival (OS) by early ASCT vs. no early ASCT overall and within age subgroups. The Kaplan-Meier method was used to estimate survival distributions and Cox regression for hazard ratio (HR) estimates. The landmark analysis included only patients surviving the first four cycles of therapy. Results: 21% of patients opted for early ASCT (n=90). At baseline (four cycles prior), early ASCT patients were younger (median 57.5y vs 66y), more fit (ECOG PS 0 45% vs 56%) and with less aggressive disease (ISS Stage 3 12% vs 28%). Median treatment duration was 7.6m for no early ASCT patients. The 1, 2, 3, 4, and 5-year survival probability estimates were higher for early ASCT vs. no early ASCT at 99%, 93%, 91%, 85%, and 80% vs. 94%, 84%, 75%, 65%, and 57%. The median OS in the early ASCT vs. no early ASCT was not reached vs. 5.8 years, respectively (Table 1). The survival hazard ratio (HR) for early ASCT was 0.55 [95%CI (0.38-0.80)]. In a further subgroup analysis of patients </= 65, 5-yr survival probability of those who had early ASCT vs. no early ASCT was 79% [95%CI (67-87)] vs. 62% [95%CI (54-69)], respectively. In patients </= 65, median OS in the early ASCT vs. no early ASCT was not reached vs. 7.4 years and the survival HR was 0.74 [95%CI (0.48-1.15)]. For patients >65, 5-yr survival probability of those who had early ASCT vs. no early ASCT was 83% [95%CI (56-94)] vs. 52% [95%CI (45-59)], respectively. In patients >65, median OS in the early ASCT vs. no early ASCT was not reached versus 5.2 years and the survival HR was 0.38 [95%CI (0.17-0.87)]. In all age groups, overall response rate was similar prior to the decision of proceeding with ASCT vs. no early ASCT. In a multivariable model adjusting for baseline prognostic factors, early ASCT retained marginal significance. Conclusions: The landmark analysis demonstrated that patients opting for ASCT after induction Ld/LD had a higher 1, 2, 3, 4, and 5- year survival probability and improvement in median OS regardless of DEX dose density. Results were stronger within the older age cohort and upheld in adjusted models. Limitations include lack of randomization and data on salvage therapy. At a time when lenalidomide and dexamethasone as induction is gaining worldwide acceptance in all age groups, early ASCT is safe and efficacious and should remain a standard of care for newly diagnosed MM even in the era of novel therapies. Table 1. Survival Probabilities (Time from Registration) for all Patients Included in the Landmark Analysis Median 1 year 2-year 3-year 4-year 5-year N Events Median (Yrs)(95% CI) Events Survival Probability(95% CI) Events Survival Probability(95% CI) Events Survival Probability(95% CI) Events Survival Probability(95% CI) Events Survival Probability(95% CI) No Early ASCT All 341 195 5.78(5.11 - 6.59) 22 0.94 (0.90 - 0.96) 53 0.84 (0.80-0.88) 84 0.75 (0.70-0.79) 119 0.65 (0.59-0.69) 144 0.57 (0.51 - 0.62) Early ASCT All 90 34 NR 1 0.99 (0.92 - 1.00) 6 0.93 (0.86 - 0.97) 8 0.91 (0.83 - 0.95) 13 0.85 (0.76 - 0.91) 18 0.80 (0.69 - 0.87) NR = not reached Disclosures Biran: Celgene: Speakers Bureau. Siegel:Celgene Corporation: Consultancy, Speakers Bureau; Amgen: Speakers Bureau; Takeda: Speakers Bureau; Novartis: Speakers Bureau; Merck: Speakers Bureau. Fonseca:Millennium: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Applied Biosciences: Membership on an entity's Board of Directors or advisory committees; Onyx/Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Binding Site: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding. Vesole:Idera Pharmaceuticals: Research Funding; Celgene Corporation: Speakers Bureau. Williams:Celgene: Consultancy, Research Funding. Abonour:Celgene: Research Funding, Speakers Bureau.

Abstract Background: Outcomes in multiple myeloma (MM) have significantly improved, leading to higher prevalence of this disease. Increasing efforts have been made by various agencies to educate patients (pts), manage quality of life (QoL) and survivorship. A global impact of these efforts including pt awareness, disease knowledge and participation in their care, as well as the physical and emotional impact of MM and its treatments (Rx) has not been assessed. We undertook an international, pt-reported survey to investigate these factors and understand any underlying disparities. Methods: A 61-question patient-reported questionnaire (MM-Q), addressing global aspects of MM pts care (components in Figure 1) was used. MM-Q was administered in collaboration with the International Myeloma Foundation (IMF). To limit responses by MM pt only, “SmartPatient” MM community members and IMF Support Group Leader list were invited to complete the survey. Some of the questions were mandatory, and those with missing responses were withdrawn from the final analysis of that pts MM-Q. Categorical and continuous variables were compared among groups using the Chi-square and Kruskal-Wallis tests, respectively using SAS software (v9.3) with a two-sided significance level of 0.05. Results: Survey responses are available from 894/1240 (72%) individuals thus far. Average survey completion time was 16 minutes. Data from 746 MM-Q was included in this analysis with 466 (62.5%) complete responses. Pts from United States (US) represented 85.7% of the responders (majority from New York State). Ethnicity (n=590) was reported as non-Latino by 97%, race (n=580) was reported as White by 95%, family history of MM was reported by 19 pts and 81 reported prior history of a primary malignancy (most common, 37% non-melanoma skin cancer). Living situation questions (n=538) revealed majority were in a household of 2 (62%), were unemployed/on public assistance (53.5%), travelled alone to medical appointments (74%), with travel times varying from <30 min (55%) to >1 hr (17%). Majority (83%) had no prior knowledge of MM, 63% were patient support group members, and 92% did MM-related research on internet. With respect to MM Rx (n=524), 70% had been on Rx within 3 months and 12% reported non-compliance. Prior Rx included thalidomide (30%), lenalidomide (66%), pomalidomide (11.5%), bortezomib (63.5%), carfilzomib (11%), steroids (100%), and clinical trial participation in 25% pts. Side effects from Rx/QoL in prior 3 months (n=403) are summarized in figure 2. Pts satisfaction with Rx/treating staff (n=378) revealed majority felt their Rx to be effective (92%), right for them (87%) and side effects were as expected (84%). In general, pts acknowledged positive attributes of the Rx staff (worked towards same goal; 91%, participated in decisions; 81%, honesty 89%, confidence; 92%), and their doctor's explanations regarding Rx (benefits; 84%, side effects; 74%, test results; 83%), with the exception of emotional effects of Rx (48%). 94% pts rated their care as good/excellent and 95% were willing to participate in a follow-up survey. Stratification of statistically significant responses by geographical categories, age and time since diagnosis are shown in table 1 and analysis by occupation and educational status is ongoing. Conclusions: We conducted a large patient-reported survey to understand the current state of awareness among MM pts and a global impact of the diagnosis and its Rx on them. We showed that majority of pts who accessed the survey responded (72%), which may be a product of literacy, education and access to technology. Majority of the pts were White and non-Latino, highlighting the possible role of access and awareness in ethnic minorities. We report the large prevalence of psychophysical burden of MM and its Rx in MM pts. In general, MM pts had a high rate of satisfaction related to the Rx and their healthcare providers, but the frequency of discussion regarding emotional effects of Rx between doctors and pts was conspicuously low (48%) and the more recently diagnosed pts were less likely to be satisfied with their treating staff. We also demonstrated significant behavioral pattern differences in geographical, age and time-since-diagnosis subgroups, some of which may be sociocultural, while others may be a result of more patient awareness and understanding of the disease. This knowledge will be very helpful in devising MM survivorship strategies. Disclosures No relevant conflicts of interest to declare.