ALBERT

Description: Abstract 4953 Background: Shared decision-making between patients and physicians is broadly advocated in medicine, however little research is available to understand whether this approach would be desirable to all patients regardless of disease type and severity or individual patient characteristics. While clinical decision-making in high-risk myelodysplastic syndromes (MDS) is critical for a number of reasons including: associated comorbidity, symptom burden, and limited life expectancy, no evidence-base data currently exist on patients' preferences. Aim: The objective of this study is twofold: 1) to investigate to what extent high-risk MDS patients prefer to be involved in treatment decision making during consultation just after diagnosis; 2) to identify possible clinical, socio-demographic and patient-reported health status factors associated with patients' preferences for involvement in treatment decisions. Patients and Methods: Data were gathered through an ongoing international prospective observational study involving 15 countries that recruits newly diagnosed patients with intermediate-2 or high-risk IPSS score. All patients were classified according to the WHO histology classification. During the first encounter with their treating physicians, discussing treatment options just after diagnosis, patients were administered a previously internationally validated “control preference scale”. This scale broadly categorizes patients into one of three roles depending on the extent of their preferred involvement in treatment decision-making: “active” (where the patient themselves prefer to decide on which would be the most appropriate treatment option for themselves); “collaborative/shared” (where the patient and the doctor jointly decided on the most appropriate treatment option); “passive” (where the patient prefer to leave decision on the most appropriate treatment option to the doctor). Associations with the following variables were investigated: performance status, comorbidity (“Hematopoietic Cell Transplantation”-“Comorbidity index”), living arrangements, age, gender, education, cultural group, IPSS risk category, evolution from lower IPSS risk scores and patient-reported symptoms (using symptom scales of the EORTC QLQ-C30). Descriptive statistics were used and Mann-Whitney U-test, Kruskall-Wallis test and Fisher's exact test were used as appropriate to test statistical significance of performed comparisons. Results: Study population included overall 121 patients (38% female and 62% male). Mean age of patients was 69 years (min:31.3 max: 87.9) and 80% were diagnosed with IPSS int-2 risk score and 20% with IPSS high risk score. Twenty-six percent evolved from lower IPSS risk scores, while 74% were newly diagnosed with higher-risk. Forty-nine percent favored a passive while only 13% preferred an active role in treatment decision-making; the remaining 38% favored a collaborative/shared decision-making approach. Investigation of factors possibly related to preferred roles, found that passive role was significantly associated with lower education levels (P=.04). Among lower educated patients, 62.5% preferred a passive role compared with only 5% preferring an active role. When investigating relationships with patient-reported symptoms, a general trend for patients preferring a passive role, showing worse outcomes, was also evident. Higher symptom mean scores were found for passive vs. active role groups, being respectively: 46 (sd.26.6) vs. 37 (sd.29.9) for fatigue; 20 (sd.31.8) vs. 2 (sd.8.6) for constipation; 34 (sd.33) vs. 24 (sd.29.5) for dyspnea. Exploratory analysis showed that overall mean symptom score was statistically significant worse in patients preferring a passive role vs. those preferring an active role (P=.01). While other trends of associations were noted, these were not statistically significant. Conclusion: This is the first evidence suggesting that a consistent percentage of high-risk MDS patients prefer a passive role when discussing treatment options with their treating physicians at the time of diagnosis. There is also an indication that these patients are those with lower education levels and presenting with a higher symptom burden. Results need to be confirmed in a larger sample size. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4619 Background: Ofatumumab is a fully-humanized anti-CD20 monoclonal antibody approved in refractory CLL. The combination of high-dose methylprednisolone (HDMP) and anti-CD20 monoclonal antibody rituximab has previously shown positive results in high-risk refractory CLL. Herein we report our institutional experience with the combination of ofatumumab and HDMP for the treatment of patients with relapsed or refractory CLL. Methods: Between October 2009 and June 2011, 10 consecutive patients with relapsed or refractory CLL received HDMP and ofatumumab at Moffitt Cancer Center. HDMP was dosed at 1 g/m2 IV weekly for 3 weeks every 28 days for two cycles, then monthly for 3 cycles. Ofatumumab was administered according to package insert instructions along with prophylactic antimicrobials. The primary endpoint was to evaluate response as defined by the updated National Cancer Institute Working Group Guidelines (NCIWG 2008). Secondary objectives were to assess treatment tolerance and toxicity. Descriptive statistics were used for baseline characteristics and response rates. Results: Eight of ten patients were male, with a median age of 60 years (range 43–81). All patients were previously treated with rituximab, and were intolerant to or failed fludarabine and/or alemtuzumab. The median number of prior treatments was 3.5 (range 1–5). Seven patients had high-risk prognostic markers including unfavorable cytogenetics or unmutated IgVH. Six patients had 17p deletion, 2 patients had 11q deletion, and 3 patients had an unmutated IgVH (6 patients had two prognostic markers). Eight patients were able to complete all planned treatments. One patient discontinued treatment due to worsening performance status and 1 patient discontinued treatment due to progressive disease. HDMP and ofatumumab were used as a bridge to allogeneic hematopoietic stem cell transplant in 4 patients. Based on NCIWG 2008 criteria, 2 patients had a partial response (PR), 1 patient had progressive disease (PD), and 6 patients had stable disease (SD). Five patients with stable disease had a clinical decrease of lymph nodes or a decrease in lymphocyte counts. Despite the use of prophylactic antimicrobials severe infectious complications occurred in 40% of patients. Infections included 1 patient with norovirus, 1 patient with cytomegalovirus viremia and a fusarium infection of the neck, 1 patient with aspergillus pneumonia, Pseudomonas aeruginosa bacteremia, and an Escherichia coli bacteremia, and 1 patient with a necrotizing pneumonia. Conclusion: This data demonstrates the benefit of HDMP and ofatumumab combination in patients with heavily pretreated CLL. The combination of ofatumumab and HDMP has a role as salvage therapy and as a bridge to allogeneic stem cell transplant. The incidence of infection was high despite the use of prophylactic antibiotics. Aggressive antibiotic prophylaxis is warranted including coverage for mould infections. Disclosures: Off Label Use: Ofatumumab in combination with high dose methylprednisolone for the treatment of relapsed/ refractory CLL. Pinilla-Ibarz:GSK: Speakers Bureau.

Description: Autologous stem cell transplantation (ASCT) has been demonstrated to prolong survival of Multiple Myeloma (MM) patients, but the benefit of this therapy for elderly patients has not been well established. Randomized data is available for patients up to 65 years of age; however, older patients have been offered autologous SCT provided they fulfill criteria for fitness at different institutions. We conducted a retrospective analysis of 214 MM patients treated with ASCT at our institution from 2001–2006. The objective of this study is to determine if age is a prognostic factor for overall survival (OS) and progression-free survival (PFS) in this patient population. Eight potential risk factors along with 3 age variables (≥65, ≥70 or age in years) were studied using backward elimination (BE) Cox model for the age terms. Age ≥ 65 was the best variable for OS and PFS, with the other two age terms dropping out. We examined 8 parameters [e.g gender, stage at diagnosis, lines of therapy, disease status at the time of transplant, conditioning regimen, time from diagnosis to transplant, and HSCT-comorbidity index and CIRS-G index, to account for co-morbidity] and clinical outcomes [e.g. length of hospital stay (LOS), time to neutrophil engraftment, PFS, and OS]. PFS and OS were calculated from the time of transplant to the time of event occurrence. One-hundred and ten patients (45 female, 65 male), with median age 68 (range 65–77) were ≥65 years (old cohort). One hundred and four patients (46 female, 58 male) with a median age 55 (range 36–64) were 0.5 × 109/L was 12 days (range 6–40 and 9–21) for both cohorts. Transplant-related mortality was (4.7 vs 1.9%) and response to transplant was [CR + VGPR (33 vs 40%), PR (31 vs 24%), SD+ PD (28 vs 29%)]. Median PFS was 14.8 months (range 12.3–20.3) and median OS was 36.8 months (range 29.4–46.8) for the old cohort. Median PFS was 24.4 months (range 16.6–31.5) and median OS was 47.9 months (range 43.8–74.3) for the young cohort. Male gender (HR1.8, 95%CI 1.7–2.8, p=0.0075), HSCT co-morbidity score (HR 1.11, 95%CI 0.9–1.2 p=0.06) were negative prognostic factor for OS, and age ≥65 was found to be the strongest negative prognostic factor influencing OS (HR 2.03, 95%CI 1.3–3.1, p=0.0014) and PFS (HR 1.86, 95%CI 1.3–2.7, p=0.0008). CONCLUSION: ASCT remains a feasible and safe therapy for elderly for multiple myeloma patients, but our experience suggests that age significantly influences PFS and OS in this population.

Description: Abstract 4880 Introduction: The standard of care for aggressive NHL is treatment (tx) with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) with rituximab (R). Improved outcomes are associated with retention of dose and schedule. Pegfilgrastim prophylaxis reduces the severity and duration of neutropenia, contributing to fewer dose delays and reductions and higher RDI. A retrospective analysis of pegfilgrastim NHL clinical trials showed that pegfilgrastim primary prophylaxis maintained RDI for CHOP/CHOP-R; a greater number of younger than older pts had 〉 85% RDI (Mo et al. Pan Pacific Lymphoma Conference 2011; poster). Here we further examine the association of age with RDI for CHOP/CHOP-R in NHL pts receiving pegfilgrastim. Methods: This retrospective analysis pooled data from 5 pegfilgrastim NHL clinical trials (1 single-arm and 4 randomized controlled studies). Pts received up to 6 cycles of CHOP/CHOP-R every 2 (Q2W) or 3 (Q3W) weeks. Data from the pegfilgrastim primary prophylaxis tx arms were combined. RDI and the incidence of dose delay, reduction, discontinuation, and adverse events (AE) leading to dose alteration/discontinuation were analyzed in the CHOP/CHOP-R regimens combined and stratified by age group (〈 65, 65–75, and 〉 75 years [yr] ) and schedule (Q2W and Q3W). RDI during tx exposure and RDI adjusted by the planned 6 cycles of tx were calculated. Overall RDI of the regimen was calculated as the average of RDI of cyclophosphamide and doxorubicin. Dose delay: 〉 3 days of delay for any cycle after cycle 1. Dose reduction: ≥ 20% reduction from the planned dose of cyclophosphamide or doxorubicin for any cycle. Dose discontinuation: not completing all planned 6 cycles of tx for reasons other than death/disease progression. RDI was also evaluated with a multiple regression model using tx group, age, stage, sex, race and comorbidity as explanatory variables. Results: In the Q3W regimen (N = 137), 50% of pts were women, 36% had stage IV disease, and 23% were 〉 75 yr. In studies with available histology data, most pts had diffuse large B cell lymphoma. The incidence of pts with 〉 85% RDI during tx exposure: 89%, 86% and 81% for pts 〈 65, 65–75 and 〉 75 yr, respectively. The incidence of pts with 〉 85% adjusted RDI: 74%, 55% and 47%, respectively. The incidence of pts who completed all 6 cycles of tx: 78%, 56% and 47%, respectively. The incidence of dose reduction: 7%, 21% and 13%, respectively. The incidence of dose discontinuation: 19%, 36% and 47%, respectively. The incidence of dose delay was similar among age groups. Multiple regression analysis showed age and cancer stage as potential factors associated with RDI (p = 0.0290 and 0.0145, respectively). The table shows AEs leading to dose alteration/discontinuation. Q2W data will be presented separately. Conclusions: In this pooled population the incidence of pts with 〉 85% RDI adjusted by the planned 6 cycles of tx was lower in older pts as fewer older pts completed all 6 cycles of tx. Pts 〈 65 yr had a lower incidence of AE leading to dose alteration/discontinuation. The AE profile was widely spread across hematological and non-hematological toxicities. Unlike prior reports where myelosuppression frequently caused reduced RDI, myelotoxicity was an infrequent cause of therapy alteration/discontinuation with pegfilgrastim primary prophylaxis (〈 7%). Pegfilgrastim use in elderly pts maintained RDI during tx exposure. Further research is needed to address non-hematologic causes of tx interruptions in elderly pts receiving CHOP based chemotherapy. Disclosures: Balducci: Jennsen: Honoraria; Novartis: Honoraria; Cephalon: Honoraria; Amgen Inc.: Honoraria. Mo:Amgen Inc.: Employment, Equity Ownership. Abella:Amgen Inc.: Employment, Equity Ownership.

Description: Introduction: Although non-Hodgkin’s lymphoma (NHL) is frequently diagnosed in older patients, few randomized clinical trials are conducted in this setting. Furthermore, older patients who are included in clinical studies are a highly selected group and are not likely to be representative of patients treated in the community. Increased age is an established risk factor for chemotherapy-induced neutropenia, and older patients often receive suboptimal doses of chemotherapy as a result, especially in community practice (Lyman et al, J Clin Oncol2004;22:1–10). In a large (n=528) study of older patients with diffuse large B-cell lymphoma receiving CHOP or R-CHOP with no cycle-1 growth factor, 41% of patients had febrile neutropenia over all cycles and 20% in cycle 1 (Morrison et al, ASH 2004 poster). The benefit of pegfilgrastim in supporting moderately to highly myelosuppressive chemotherapy regimens has previously been shown. Methods: As part of a large (n=852), prospective, randomized, open-label study, we assessed the effectiveness of first-cycle pegfilgrastim among patients ≥ 65 years old receiving chemotherapy for NHL in community practice. Patients were randomized to 1 of 2 treatment arms - pegfilgrastim in first and subsequent cycles (Arm A) or no pegfilgrastim in cycle 1 with subsequent use at the physician’s discretion (Arm B). Results: The primary analysis set included 146 patients with NHL, 73 per treatment arm. Median age was 73 years, range 65 to 87, with nearly 75% of patients aged 70 and older. R-CHOP was the most common chemotherapy, administered to 82% of patients. The overall incidence of febrile neutropenia was significantly lower for patients in Arm A (15%; [95% confidence limit (CL): 8, 25]) compared with patients in Arm B (37% [95% CL 26, 49]; p=0.0043). The first cycle incidence of febrile neutropenia was also lower in Arm A (7% [95% CL: 2, 15]) than in Arm B (25% [95% CL: 15, 36]), as was the overall incidence of hospitalization due to neutropenia-related events (17% [95% CL: 10, 28] vs 37% [95% CL: 26, 49]). Pegfilgrastim was administered frequently in Arm B, with 61% of patients initiating treatment in cycle 2, and 91% of patients (29/32) receiving pegfilgrastim by cycle 6. The main reasons for pegfilgrastim use in Arm B were grade 3/4 neutropenia, followed by febrile neutropenia. Dose reductions occurred in 16% of Arm A patients (95% CL: 9, 27) and in 8% of Arm B patients (95% CL: 3, 17) and dose delays occurred in 29% (95% CL: 19, 41) and 23% (95% CL: 14, 35) respectively; however, 19% of patients in Arm B discontinued from the study after cycle 1 compared with only 5% in Arm A, confounding the incidence of both parameters. Adverse event profiles were similar between the 2 treatment arms and were consistent with the population under study. Conclusions: The results of this study support the feasibility of conducting community-based trials in older patients, demonstrate that older patients can safely receive myelosuppressive chemotherapy, and show the effectiveness of first-cycle use of pegfilgrastim among older patients with NHL treated in the community setting.