Citations 261

Rituximab-based maintenance therapy in Waldenström macroglobulinemia: A case control study.

Journal of Clinical Oncology | March 12, 2020 | Volume: 37 | Issue: 15_suppl | Pages: 7559-7559

10.1200/jco.2019.37.15_suppl.7559

7559 Background: Waldenström macroglobulinemia (WM) is a rare indolent lymphoma commonly treated with rituximab (R)-based therapy. The use of rituximab maintenance (mR) in WM is controversial. We present a case-control study of patients (pts) with WM treated with mR. Methods: Pts evaluated at Mayo Clinic, Rochester with active WM that received mR between 1/2000 & 6/2018 were included. Cases comprised pts who received mR following R-based induction as primary therapy. Cases were matched based on the time of diagnosis in 1:2 ratio with a control group treated with R-based primary induction therapy without mR. Time to event analyses were performed from initiation of R-based induction. Results: Of 776 pts with active WM, 42 (5%) cases received mR and 84 pts were selected as controls. The median follow-up and the proportion of high risk pts were comparable between the two cohorts (Table). Pts in the mR cohort show a trend toward longer time to next therapy (TTNT) and a significantly longer overall survival (OS) compared to the control group (Table). The R-based induction therapies were comparable in the two cohorts (p = 0.6). Median duration of mR was 1.9 yrs (95% CI 1.6-2) and mR was used most frequently every (q) 2 (range 1-6) months. Of the 42 mR pts, 25 (60%) received an R-based combination for induction and 17 (40%) received R monotherapy as induction. Five (12%) pts discontinued mR due to toxicity, infections were reported in 13 pts (31%) during mR therapy and 3 pts (7%) received IVIg infusions for recurrent infections. Conclusions: R-based induction followed by mR demonstrates a longer OS in WM compared to R-treated control population not receiving mR, albeit at a high rate of infections. Despite limitations of a retrospective study, with a heterogeneously treated cohort, these data add to the body of literature supporting Rituximab maintenance. Results from an ongoing randomized controlled trial are awaited. [Table: see text]
Extranodal (EN) and spleen disease by FDG-PET/CT is associated with early clinical failure in untreated follicular lymphoma (FL).

Journal of Clinical Oncology | March 12, 2020 | Volume: 37 | Issue: 15_suppl | Pages: 7554-7554

10.1200/jco.2019.37.15_suppl.7554

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]
Impact on survival of surveillance imaging after first remission in follicular lymphoma.

Journal of Clinical Oncology | March 12, 2020 | Volume: 37 | Issue: 15_suppl | Pages: 7536-7536

10.1200/jco.2019.37.15_suppl.7536

7536 Background: While most patients (pts) with follicular lymphoma (FL) achieve an initial response to treatment, the majority relapse. Recently, Goldman et al. reported that surveillance imaging (SI) in FL is not associated with improved post-relapse outcomes and is frequently associated with false positive scans (ASH 2017). The goal of this study was to validate these findings. Methods: Pts 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. Pts eligible for this study had biopsy proven FL grade 1, 2, or 3a who had achieved a response after induction therapy and later relapsed. Initial and post-treatment management was per treating physician. Medical records were re-reviewed in pts with events for clinical details at relapse in relationship to planned follow-up visits and SI. Relapse detection was categorized either by clinical suspicion (CS) via history, exam, and/or labs; or by SI in an asymptomatic pt. Univariate survival analysis was conducted for each variable. The hazard ratio with 95% confidence interval based on Cox Proportional Hazard models was presented along with the log rank test p-value. Kaplan-Meier plots were produced to evaluate the difference in overall survival (OS) between groups. Results: 1121 FL pts were enrolled in MER from 2002-2015, of which 117 were eligible. Median age at diagnosis was 60 years (range 35-83), and 61% were men. Median time to relapse of the 117 pts was 26 months (range 9-125). At a median follow-up from relapse of 69 months (range 0.23-179), 26 pts died. Pts completed a median of 3 imaging studies (range 0-15) during post-induction surveillance. 63 relapses (56%) were detected based on CS; 50 (44%) were detected by SI; and 4 were unknown. There was no difference in OS from relapse for those with relapse detected via CS vs. SI (HR = 0.98 [0.45,2.12], p = 0.96). Conclusions: Routine SI does not appear to improve survival outcomes in FL after achieving first remission, and its common practice should be questioned. Further investigation of prognostic markers to identify high-risk FL pts who may benefit from SI is needed.
Outcomes with rituximab plus bendamustine (R-Benda), dexamethasone, rituximab, cyclophosphamide (DRC), and bortezomib, dexamethasone, rituximab (BDR) as primary therapy in patients with Waldenstrom macroglobulinemia (WM).

Journal of Clinical Oncology | March 12, 2020 | Volume: 37 | Issue: 15_suppl | Pages: 7509-7509

10.1200/jco.2019.37.15_suppl.7509

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]
A novel qualitative methodology study to characterize discrimination and inclusion among hematology/oncology trainees.

Journal of Clinical Oncology | March 12, 2020 | Volume: 37 | Issue: 15_suppl | Pages: 10530-10530

10.1200/jco.2019.37.15_suppl.10530

10530 Background: Learner wellbeing may be adversely affected by the experience of discrimination. Eliciting details from this vulnerable population about these experiences is a challenge. This study characterizes trainee experiences of discrimination and inclusion to inform graduate medical education (GME) policies and practice. Methods: Anonymous semi-structured, private phone interviews were conducted with fellows after informed consent. No identifying information was exchanged and the interviewer had no supervisory role over learners. Demographic information was obtained via anonymous online survey. Results: Of 29 fellows approached, 20 consented; 17 interviewed (10 men; median age 32 years). Racial & ethnic distribution: 6 Asian, 2 Black, 2 Multi-racial, 4 White, 3 Hispanic/Latino. All fellows reported discriminatory behavior that they either experienced or witnessed. Incidents of discriminatory behavior towards trainees were more common from patients (pts) (n = 41) than staff (n = 12). Discrimination from pts included requesting a different physician based on accent (n = 13), race (n = 11), perceived avoidance of a trainee considered “different” (n = 11), sex (n = 5), & ethnicity (n = 4). Six trainees were aware of policies against pt discrimination but only 1 trainee reported an incident. Trainees did not report because of the nature of incidents (micro aggressions that are difficult to characterize) and sense of futility of reporting. Discriminatory behavior from staff was based on perceived micro aggressions (n = 4), sex (n = 3), ethnicity (n = 3), ageism (n = 1), and sexual orientation (n = 1). Impact on trainees ranged from negative (personal anguish) to positive (motivation to improve communication). Coping mechanisms included debriefing with family/trainees and focusing on good pt experiences. Trainees felt that having diverse co-fellows, involvement on committees, and supportive program leadership promoted inclusivity. Conclusions: Our study found that discriminatory behavior towards trainees is common. Our methodology allows for honest & safe discussions. GME programs must assess their learning climate with respect to bias/inclusivity & develop appropriate processes.
Correlation of chemotherapy delivery and survival outcomes of follicular lymphoma in the immunchemotherapy era.

Journal of Clinical Oncology | March 12, 2020 | Volume: 31 | Issue: 15_suppl | Pages: 8563-8563

10.1200/jco.2013.31.15_suppl.8563

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.
Utility of post-therapy surveillance scans in DLBCL.

Journal of Clinical Oncology | March 12, 2020 | Volume: 31 | Issue: 15_suppl | Pages: 8504-8504

10.1200/jco.2013.31.15_suppl.8504

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.
Widespread use of complementary and alternative medicine (CAM) among non-Hodgkin lymphoma (NHL) survivors.

Journal of Clinical Oncology | March 11, 2020 | Volume: 30 | Issue: 15_suppl | Pages: 9057-9057

10.1200/jco.2012.30.15_suppl.9057

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.
Body mass index (BMI) and physical activity in long-term lymphoma survivors: A pilot study

Journal of Clinical Oncology | March 9, 2020 | Volume: 24 | Issue: 18_suppl | Pages: 17511-17511

10.1200/jco.2006.24.18_suppl.17511

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.
Utilization of Cardiac Surveillance Tests in Survivors of Breast Cancer and Lymphoma After Anthracycline-Based Chemotherapy

Circulation: Cardiovascular Quality and Outcomes | February 28, 2020 | Volume: 13 | Issue: 3 | Pages: No page available

10.1161/circoutcomes.119.005984 | PMID 32106704

Background: The National Comprehensive Cancer Network and American Society of Clinical Oncology recommend consideration of the use of echocardiography 6 to 12 months after completion of anthracycline-based chemotherapy in at-risk populations. Assessment of BNP (B-type natriuretic peptide) has also been suggested by the American College of Cardiology/American Heart Association/Heart Failure Society of America for the identification of Stage A (at risk) heart failure patients. The real-world frequency of the use of these tests in patients after receipt of anthracycline therapy, however, has not been studied previously. Methods and Results: In this retrospective study, using administrative claims data from the OptumLabs Data Warehouse, we identified 31 447 breast cancer and lymphoma patients (age ≥18 years) who were treated with an anthracycline in the United States between January 1, 2008 and January 31, 2018. Continuous medical and pharmacy coverage was required for at least 6 months before the initial anthracycline dose and 12 months after the final dose. Only 36.1% of patients had any type of cardiac surveillance (echocardiography, BNP, or cardiac imaging) in the year following completion of anthracycline therapy (29.7% echocardiography). Surveillance rate increased from 37.5% in 2008 to 42.7% in 2018 (25.6% in 2008 to 40.5% echocardiography in 2018). Lymphoma patients had a lower likelihood of any surveillance compared with patients with breast cancer (odds ratio, 0.79 [95% CI, 0.74–0.85]; P <0.001). Patients with preexisting diagnoses of coronary artery disease and arrhythmia had the highest likelihood of cardiac surveillance (odds ratio, 1.54 [95% CI, 1.39–1.69] and odds ratio, 1.42 [95% CI, 1.3–1.53]; P <0.001 for both), although no single comorbidity was associated with a >50% rate of surveillance. Conclusions: The majority of survivors of breast cancer and lymphoma who have received anthracycline-based chemotherapy do not undergo cardiac surveillance after treatment, including those with a history of cardiovascular comorbidities, such as heart failure.