Citations

7556 Background: The frontline treatment for advanced follicular lymphoma has evolved with the introduction of maintenance therapy, bendamustine (Benda), obinutuzumab (G), and lenalidomide (Len). We conducted a network meta-analysis of phase 3 randomized controlled trials (RCTs) to identify the regimens with superior efficacy. Methods: Data were extracted from 7 RCTs (FOLL05, StiL NHL1, BRIGHT, PRIMA, GALLIUM, StiL NHL7, and RELEVANCE). Progression-free survival (PFS) was compared between 11 regimens with different immunochemotherapy and maintenance strategies. To incorporate direct and indirect comparisons, random-effects Bayesian network meta-analyses were conducted after adjusting for study-wise variation. The posterior inference was derived based on Markov chain Monte Carlo methods and implemented using JAGS v4.3.0. Pairwise comparison of hazard ratios (HRs) and 95% credible intervals (CIs) were calculated. Results: PFS HRs of other regimens compared to the reference regimen are summarized in the Table. Compared to Rituximab(R)-Benda, R-CHOP had inferior PFS, R-CHOP-R, G-CHOP-G, and R-Len-R had similar PFS, while R-Benda-R, R-Benda-R4 and G-Benda-G had better PFS. Compared to R-CHOP-R, G-CHOP-G and R-Len-R had similar PFS, while R-Benda-R, R-Benda-R4 and G-Benda-G had better PFS. In addition, the PFS for G-Benda-G was similar to R-Benda-R4 (HR 0.94, 95% CI 0.78-1.09) but better than R-Benda-R (HR 0.82, 95% CI 0.75-0.97). Conclusions: Compared with the commonly used R-Benda and R-CHOP-R regimens, G-CHOP-G, R-Benda-R and R-Benda-R4 had better PFS, while the chemotherapy-free regimen R-Len-R had similar PFS. [Table: see text]

7554 Background: Predicting early clinical failure in patients with untreated FL is important but difficult. Lymphoma involvement of EN sites is better detected by FDG-PET/CT than CT alone, but PET parameters are not part of the usual predictive indices. We aimed to determine the incidence and patterns of spleen and EN disease using PET/CT, and learn if they are useful in predicting early clinical failure. Methods: PET/CT images from 613 cases of newly diagnosed FL between 2003 – 2016 were retrospectively reviewed. The location, pattern, and number of EN sites, as well as splenic involvement, were recorded. Associations with outcomes were assessed using event-free survival (EFS) and overall survival (OS). Results: 49% (301/613) of patients had PET/CT-detected EN involvement, and 28% (171/613) had spleen involvement. Presence of ≥2 EN sites, spleen, bone, or soft tissue involvement, as well as a multifocal on diffuse pattern of bone involvement by imaging, were univariate predictors of EFS; presence of ≥2 EN sites and bone involvement pattern were also predictive of OS. In a multivariate analysis with FLIPI-2 factors, spleen involvement, pattern of bone involvement, and soft tissue involvement independently predicted a lower EFS (Table). When the multivariate analysis was performed using PRIMA-PI factors, the presence of ≥2 EN sites was an adverse independent prognostic factor for OS (HR 2.28; 95% CI 1.01-5.18; p=0.05). Conclusions: Baseline PET/CT identifies EN and spleen sites of disease that can predict early clinical failure of FL. These results may be useful to better identify high-risk patients and guide appropriate therapy. [Table: see text]

7509 Background: Waldenstrom macroglobulinemia (WM) is a rare lymphoma for which scant comparative data exist to guide frontline therapy. Herein, we compare 3 commonly used regimens in WM: R-Benda, DRC, and BDR in frontline setting. Methods: Patients (Pts) with active WM seen at Mayo Clinic between 2000 & 2018 who received R-Benda, DRC or BDR as primary therapy were included in this retrospective study. Response rates were assessed by Consensus Criteria. All time to event analyses were performed from the frontline therapy, using Kaplan-Meier method. Results: The study included 172 pts with active WM (R-Benda, n=67, DRC, n=75, BDR, n=30).The median follow-up for the entire cohort was 3.7 years (y) (95% CI 3.7-3.0). Baseline characteristics, including IPSS, and time to frontline therapy from WM diagnosis were similar across the 3 cohorts. Clinically relevant endpoints are shown in the Table. Hematologic and non-hematologic toxicities were similar across the 3 groups. Grade 3 neuropathy requiring treatment discontinuation was encountered in 13% pts treated with BDR. 56 pts received subsequent salvage therapy [(10% in R-Benda arm, 44% in DRC arm, & 53% in BDR arm]; 29% pts in the R-Benda arm and 30% pts in DRC arm received a PI-based regimen while 69% pts in the BDR arm received alkylator-rituximab based therapy. Conclusions: Outcomes (MRR, TTNT and EFS) with frontline R-Benda are superior in comparison to frontline DRC or BDR in patients with WM. Clinically relevant endpoints are not significantly different with DRC vs. BDR. The toxicity profile across the 3 groups was comparable. [Table: see text]

8563 Background: Optimal initial treatment of follicular lymphoma (FL) is unknown. Rituximab as monotherapy (R) or as a component of immunochemotherapy (R+Chemo) is established as effective and it is now reasonable to re-examine the role of chemotherapy dosing. We explored clinical features, systemic treatment and chemotherapy delivery with comparative effectiveness of delivered dose intensity (DDI) on outcomes. Methods: We reviewed the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource database along with medical records on newly diagnosed grade I-IIIa FL who received systemic therapy from 2002 to 2009. Presenting clinicopathologic factors, outcomes and systemic therapy details including doses of chemotherapy were collected. The event-free (EFS) and overall survival (OS) effects of systemic therapy and chemotherapy DDI were analyzed with multivariate Cox regression. Confounding effects of FLIPI, grade, stage, and age were considered in the analysis. Results: From 2002 to 2009, 631 newly diagnosed FL were enrolled. Median follow up duration was 52.7 months. We identified 322 grade I-IIIa FL treated with systemic therapy including 93 R and 229 R+Chemo. Age and stage were similarly distributed between the R and R+Chemo groups; however, patients in the R group had lower grade (p<0.01) and FLIPI (p=0.03). Multivariate analysis showed no significant differences in EFS (HR=1.24, p=0.28) or OS (HR=0.55, p=0.13) for R compared to R+Chemo. Among R-CVP or R-CHOP treated FL, DDI data were collected for 73 doxorubicin (dox) and 137 cyclophosphamide (cyc) patients. Eighty-five percent of patients received 90% or more pre-planned DDI. After controlling for confounding factors, higher cycDDI was associated with improved EFS (HR 0.55, P=0.04) and OS (HR 0.74, P=0.03). No significant OS or EFS effects of doxDDI were observed. Conclusions: Addition of chemotherapy to rituximab was not associated with a detectable difference in survival outcomes in grade I-IIIa FL at a median follow-up of 52.7 months. Among R+Chemo treated FL, chemotherapy was delivered completely in most patients and more completed delivery of cyclophosphamide was associated with improved EFS and OS.

8533 Background: Mantle cell lymphoma (MCL) is an aggressive form of non-Hodgkin lymphoma (NHL) with poor prognosis. The immunomodulatory agent lenalidomide shows consistent activity with tolerable safety in multiple phase II studies of relapsed/refractory aggressive NHL (NHL-002 and NHL-003) and MCL post-bortezomib (MCL-001). This pooled analysis further examined the efficacy and safety of single-agent lenalidomide in patients with relapsed/refractory MCL. Methods: Single-agent lenalidomide was given 25 mg/d PO on days 1-21 of 28-day cycles as tolerated for 52 weeks (NHL-002) or until disease progression (NHL-003 and MCL-001). All MCL patients received ≥1 prior treatment, including bortezomib in MCL-001. Efficacy data were examined by independent central review for MCL-001 and NHL-003 and by investigators for NHL-002. Results: 206 patients with relapsed/refractory MCL were studied. The median age was 67 y (range 33-84; 63% ≥65 y), 91% stage III/IV disease and 51% had received ≥4 prior regimens (76% prior bortezomib). Overall response rate (ORR) with lenalidomide was 32% (10% CR/CRu), with a median time to response of 2.1 months and median duration of response (DOR) of 16.6 months (not yet reached in patients with CR/CRu; Table). Kaplan-Meier estimates for median PFS and OS were 5.4 and 23.9 months, respectively. Mean daily dose of lenalidomide was 21 mg. Grade 3/4 AEs included neutropenia (44%), thrombocytopenia (29%), anemia (11%), and fatigue (7%). Other any-grade AEs included tumor flare reaction (7%), venous thromboembolic events (7%), and invasive second primary malignancies (3%). Conclusions: Lenalidomide produced rapid and durable responses in patients with relapsed/refractory MCL, and exhibited a predictable safety profile among 3 phase II studies of lenalidomide in heavily pretreated patients, including prior treatment with bortezomib. Clinical trial information: MCL-001: NCT00737529; NHL-002: NCT00179660; NHL-003: NCT00413036. [Table: see text]

8504 Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma. The optimal follow-up strategy for patients (pts) in remission is not clear. The goal of this study is to determine the utility of surveillance scans in a large, prospective, multi-institutional cohort of DLBCL pts. Methods: Patients were enrolled in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER), a prospective cohort of newly diagnosed lymphoma pts. All pts were followed for events including relapse, re-treatment, and death with events verified by medical records. Patients eligible for this study had biopsy proven DLBCL and were treated with anthracycline based immunochemotherapy (IC). Initial and post-treatment management was per treating physician. Medical records were re-reviewed in pts with events for clinical details at relapse and relationship to planned follow-up visits and surveillance scans. Results: 644 pts with DLBCL treated with IC were enrolled in MER from 2002-2009. Median age was 63 years (range 18-92), 54% were men, and median f/u was 59 months (range 8-116). 537 pts entered post-treatment observation; 109 (20%) of the 537 pts relapsed and 41 died from other causes. 42% of relapses were in the first 12 months following diagnosis, 27% between 12-24 months, and 31% >24 months. In the 109 who relapsed, 62% of pts (62/100, 9 unknown) presented to their physician earlier than a planned follow-up visit due to symptoms. At the time of relapse, 68% were symptomatic, 42% of pts had abnormal physical exam, and 55% had elevated LDH; 87% of pts had ≥1 of these features. Of the 38 pts with relapse detected at a planned visit, 26 had clinical features of relapse and 12 pts had relapse detected solely by planned surveillance scan; 4 pts had relapse of low-grade or other subtype and 8 had DLBCL relapse (4 of whom had equivocal/positive PET at the end of IC). Thus, surveillance scanning detected DLBCL relapse prior to clinical manifestations in only 8/537 pts (1.5%) observed post DLBCL therapy. Conclusions: The vast majority of DLBCL relapses occur outside of planned follow-up visits and are accompanied by symptoms, physical exam, or laboratory abnormalities. Routine surveillance scans post-therapy add little to detection of DLBCL relapse.

9057 Background: The incidence of CAM use among patients with cancer is higher when compared to the general population. However, there are few studies examining CAM use in NHL survivors, and limited data are available regarding beliefs in CAM. This study was conducted to examine the prevalence of CAM use in NHL, define CAM beliefs among NHL survivors, and explore differences between patients with indolent and aggressive lymphoma. Methods: Newly diagnosed lymphoma patients were prospectively enrolled within 9 months of diagnosis in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource from 2002-2008. NHL patients who completed the 3-year post diagnosis questionnaire, which includes questions regarding CAM use and beliefs, were included in this study. Chi-squared tests and Wilcoxon rank-sum tests were used to assess the association of CAM use with prognostic and demographic factors. Results: 719 patients were included with a median age of 63 years (range 22-92). 53% were male. Overall, 636 (89%) reported ever using CAM. 78% of patients used vitamins and 54% alternative therapies (chiropractic (36%) and massage therapy (24%)). Among CAM users, 141 (22%) believe CAM can assist the body to heal, 123 (19%) believe CAM can relieve cancer symptoms, 115 (18%) believe CAM use gives a feeling of control, 106 (17%) believe CAM can boost immunity, 24 (4%) believe CAM can cure cancer, and 35 (6%) believe CAM can prevent the spread of cancer. Female gender was associated with increased overall CAM use (p<0.0001) as well as use of vitamins (p<0.0001), herbal supplements (p=0.006) and alternative therapy (p=0.0002) specifically for cancer. Older age was also associated with increased vitamin use (p=0.005) and decreased herbal supplements use (p=0.008). There was no significant difference in overall CAM use between those with follicular lymphoma grades I-II (n=195, 91%) and non-relapsed diffuse large B-cell lymphoma (n=151, 87%), although massage therapy was utilized more often by FL survivors (29% versus 18%, p=0.005). Conclusions: CAM modalities are used by the majority of NHL survivors (89%). The assessment of CAM use and education regarding potential harms is imperative for the NHL survivor.

7586 Background: The immunologic mechanisms of action of rituximab have been described as complement mediated lysis, vaccine like effect, antibody-dependent cellular cytotoxicity (ADCC) and the cellular microenvironment. We hypothesized that in the treatment of follicular grade 1 lymphoma (FL), the presence of a stronger host immune status prior to rituximab therapy would result in a prolonged time to progression (TTP). As a surrogate marker for immune status, we evaluated the absolute lymphocyte count (ALC) prior to rituximab treatment. Methods: Between 1996 and 2002, 1,104 consecutive FL patients were evaluated at Mayo Clinic Rochester. Of these patients, we retrospectively analyzed a group of all FL patients who received rituximab (375 mg/m2 once a week for four weeks) alone at any time during their lymphoma treatment at the Mayo Clinic (n=79). The primary end-point was to assess the impact of ALC just prior to rituximab therapy on TTP for FL. Results: The median age of the cohort was 56.6 years (range: 25–98 years). The median follow-up was 12.5 months (range: 1–76 months). An ALC count of ≥ 890 cells/μL prior to rituximab therapy predicted a longer TTP compared with an ALC < 890 cells/μl (25 months versus 8 months, respectively, p < 0.0124). A higher complete response rate was observed in the ALC ≥ 890 cells/μL group compared with the ALC < 890 cells/μL group [15/40 (38%) vs 5/39 (13%), p < 0.035]. The groups were balanced regarding the Follicular Lymphoma International Prognostic Index (FLIPI) (p = 0.794). Multivariate analysis demonstrated ALC ≥ 890 cells/μL prior to rituximab therapy as an independent prognostic factor for TTP when compared to hemoglobin, LDH, and Ann Arbor stage. The ALC was independent of the FLIPI in multivariate analysis. Conclusions: This data supports the hypothesis that a higher lymphocyte count, as a marker of the immune status of the patient, predicts for a longer TTP following rituximab therapy. No significant financial relationships to disclose.

17569 Background: Lenalidomide is an immunomodulatory drug of the IMiD class that has activity in multiple myeloma, myelodysplastic syndromes and chronic lymphocytic leukemia. We report preliminary results of two Phase II studies assessing the safety and efficacy of lenalidomide monotherapy in subjects with relapsed/refractory indolent or aggressive non-Hodgkin’s lymphoma (NHL). Methods: Subjects with indolent (study NHL-001) or aggressive (study NHL-002) relapsed/refractory NHL following ≥ 1 prior treatment regimen with measurable disease are eligible. Subjects receive 25 mg lenalidomide orally once daily on Days 1–21 every 28 days and continue therapy for 52 weeks as tolerated until disease progression. Response and progression are evaluated using cross sectional imaging by the NCI criteria. Results: 10 subjects (2 indolent (I), 8 aggressive (A)) of a planned 80 (40 in each study) have enrolled thus far. Median age is 66 (45–80) and 7 subjects are female. Indolent histology is follicular center lymphoma grade 1, 2 (n = 2) and aggressive histology diffuse large cell lymphoma (n = 7) and follicular center lymphoma grade 3 (n = 1). Median time from diagnosis to lenalidomide monotherapy is 2.9 years (1.1–10) and median number of prior treatment regimens per subject is 3 (1–6). Median duration of follow-up is 2 months. Of eight subjects (2 I, 6 A) evaluable for response at two months, three demonstrated a decrease in their tumor burden by 72% (I), 68% (A) and 52% (A), two subjects (2 A) exhibited stable disease and three subjects (1 I, 2 A) had disease progression. Six of the ten subjects (2 I, 4 A) demonstrated no Grade 3 or 4 adverse events. Grade 3 or 4 hematological adverse events (neutropenia, thrombocytopenia) occurred in four subjects including one febrile neutropenia and one of these four subjects also exhibited Grade 3 cellulitis. No tumor flare or tumor lysis has been observed to date. Conclusions: Preliminary data of lenalidomide monotherapy in relapsed and refractory NHL are encouraging. [Table: see text]

17511 Background: There is no published data regarding BMI changes in survivors of adult lymphoma. Methods: In October of 2004, we mailed a 23-page survey to 95 randomly selected patients from a population of 2,485 of patients from the Mayo Tumor Registry who had survived lymphoma from 5 to 20 years. 56 completed the survey for a 68% participation rate. Body mass index (BMI) was calculated using clinical height and weight in the medical record at the time of diagnosis and self-reported weight in the survey response. Physical activity was self-reported. Based on their pattern of response, patients were categorized into a stage of change of current exercise (precontemplation, contemplation, preparation, action, or maintenance). Mood disturbance (depression, anxiety, and distress) and quality of life (QOL) were self-reported using the CES-D, POMS, STAI, FACT-G, and LASA questionnaires. Scores were transformed to a scale of 0–100 (higher score meaning higher functioning) to allow comparisons with a difference of 10 points considered significant. Results: The median age at completion of the questionnaire was 62 years (range: 25–85). The median time since diagnosis was 11 years (range: 6–20). Regular fitness, defined as a stage of change for exercise of action or maintenance, was reported by 48% of the respondents. The median BMI at diagnosis was 25.6 and the median at time of questionnaire was 27.0, which is a statistically significant change. Change in BMI, BMI at diagnosis, and BMI at time of questionnaire had no correlation with level of physical activity. Obese patients had a mean score of 72 points on the LASA, which was significantly lower than normal and underweight patients (mean 86) and overweight patients (mean 84). Conclusions: A small, but significant increase in body mass index was noted in long-term lymphoma survivors from the time of diagnosis to long-term follow-up. Patients who were obese at time of diagnosis may have lower quality of life down-the-road, as measured by the LASA years following treatment. This data represents the first information about body mass index in survivors of adult lymphoma. Further larger studies are needed to confirm these preliminary data and to evaluate other aspects of health behavior in long-term survivors of lymphoma. No significant financial relationships to disclose.