Citations

64 Background: The goals of our Lymphoma Survivorship Clinic (SC) are to coordinate care, educate patients, and create a survivorship care plan (SCP). The aim of this study was to determine if patient-centered outcomes are improved after a SC visit. Methods: From 11/13-5/15, surveys were mailed to recently-treated lymphoma patients who were within 4 weeks of their last visit and in remission. Quality of life (QOL) was measured with PROMIS and distress was measured with the Impact of Events scale. Responses between those who attended SC and those who were eligible but did not attend were analyzed. Results: There were 96 surveys sent to the SC group; 59 were returned (61% response rate). Of the non-SC group, 140 surveys were sent and 84 were returned (60% response rate). Mean age was 57 years (range 23-77) in the SC group and 59 years (23-88) in the non-SC group. There were more females in the SC group (52% vs 30%) but no differences in race, marital status, education, or health literacy. Those who attended the SC were more likely to recall receiving a summary of cancer treatment and recommendations for follow-up care (90% SC vs. 75% non-SC, p = 0.03). Furthermore, SC attendees were more likely to “definitely” recall discussion on improving health or preventing illness (89% vs. 53%), getting help in making changes in habits/lifestyle (76% vs. 50%), diet (80% vs. 31%), and exercise (82% vs. 51%), all p < 0.001. There were no differences in discussions regarding smoking, follow-up testing, and symptom monitoring. The SC group was less likely to need more information regarding sexuality (6% vs 20%, p = 0.045). There were no differences in need for information regarding anxiety, fitness, familial cancer risk, fertility, complementary therapies, and social issues. The SC group was slightly more confident that they could get information or advice related to cancer (completely confident 76% vs. 61%, p = 0.07). There were no differences in QOL or distress. Conclusions: A Lymphoma SC visit increased receipt of SCP and provided more information on survivorship issues, particularly health behaviors, but did not improve QOL or distress. Further study is needed to determine if this leads to long-term health benefits.

AbstractPatients with indolent non‐Hodgkin lymphoma (NHL) have multiple treatment options yet there is no consensus as to the best initial therapy. Lenalidomide, an immunomodulatory agent, has single agent activity in relapsed lymphoma. This trial was conducted to assess feasibility, efficacy, and safety of adding lenalidomide to rituximab, cyclophosphamide, and dexamethasone (LR‐CD) in untreated indolent NHL patients requiring therapy. This was a single institution phase II trial. Treatment consisted of IV rituximab 375 mg/m2 day 1; oral lenalidomide 20 mg days 1–21; cyclophosphamide 250 mg/m2 days 1, 8, and 15; and dexamethasone 40 mg days 1, 8, 15, and 22 of a 28‐day cycle. Treatment continued 2 cycles beyond best response for a maximum of 12 cycles without rituximab maintenance. Thirty‐three patients were treated. Median age was 68 (43–83 years). 39% had stage IV disease. Histologic subtypes included 8 follicular lymphoma (FL), 7 marginal zone lymphoma (MZL) (1 splenic, 2 extranodal, and 4 nodal), 15 Waldenström's macroglobulinemia (WM), 1 lymphoplasmacytic lymphoma, 1 small lymphocytic lymphoma, and 1 low‐grade B‐cell lymphoma with plasmacytic differentiation (unable to be classified better as MZL or LPL). Hematologic toxicity was the most common adverse event. Median time of follow‐up was 23.4 months (range 1.8–50.9). The overall response rate was 87.9%, with 30.3% complete response. The median duration of response was 38.7 months. The median progression free survival was 39.7 months, while median overall survival (OS) has not yet been reached. Lenalidomide can be safely added to a simple regimen of rituximab, oral cyclophosphamide, and dexamethasone and is an effective combination as initial therapy for low‐grade B‐cell NHL.

AbstractRelapsed indolent lymphoma often becomes refractory to standard chemoimmunotherapy and requires new therapeutic strategies. Targeting the PI3K/mTOR pathway in several types of lymphoma has shown preclinical and clinical efficacy providing the rationale to test this strategy in the treatment of relapsed/refractory indolent lymphomas. We investigated in a phase II open label clinical trial the efficacy and safety of single agent everolimus, an inhibitor of mTORC1, in patients with relapsed/refractory indolent lymphomas. Eligible patients received oral everolimus 10 mg daily on a 28 day‐cycle schedule. The primary endpoint was to evaluate the overall response rate (ORR) and safety of single‐agent everolimus in this patient population. Fifty‐five patients with indolent lymphoma were accrued. The median age was 67 years (range: 33‐85) with a median of five prior therapies (range: 1‐10). The ORR was 35% (19/55; 95% CI: 24‐48%), with complete response unconfirmed in 4% (2/55), and partial response in 31% (17/55). The ORR was 61% (14/23) in the patients with FL. The median time to response was 2.3 months (range: 1.4‐14.1), median duration of response of 11.5 months (95%‐CI: 5.7‐30.4), and a median progression‐free survival of 7.2 months (95%‐CI: 5.5‐12.5). The most common toxicity was hematologic with grades 3‐4 anemia, neutropenia, and thrombocytopenia documented in 15% (8/55), 22% (12/55), and 33% (18/55), respectively. There were no cases of febrile neutropenia, and eight patients discontinued therapy because of adverse events. Everolimus monotherapy is a valid therapeutic option in the relapsed and/or refractory indolent non‐Hodgkin lymphoma patients and is well tolerated.

Recent advances in follicular lymphoma (FL) have resulted in prolongation of overall survival (OS). Here we assessed if early events as defined by event‐free survival (EFS) at 12 and 24 months from diagnosis (EFS12/EFS24) can inform subsequent OS in FL. 920 newly diagnosed grade 1‐3A FL patients enrolled on the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER) from 2002‐2012 were initially evaluated. EFS was defined as time from diagnosis to progression, relapse, re‐treatment, or death due to any cause. OS was compared to age‐and‐sex‐matched survival in the general US population using standardized mortality ratios (SMR) and 95% confidence intervals (CI). We used a cohort of 412 FL patients from two Lyon, France hospital registries for independent replication. Patients who failed to achieve EFS12 had poor subsequent OS (MER SMR = 3.72, 95%CI: 2.78‐4.88; Lyon SMR = 8.74, 95%CI: 5.41‐13.36). Conversely, patients achieving EFS12 had no added mortality beyond the background population (MER SMR = 0.73, 95%CI: 0.56‐0.94, Lyon SMR = 1.02, 95%CI: 0.58‐1.65). Patients with early events after immunochemotherapy had especially poor outcomes (EFS12 failure: MER SMR = 17.63, 95%CI:11.97‐25.02, Lyon SMR = 19.10, 95%CI:9.86‐33.36; EFS24 failure: MER SMR = 13.02, 95%CI:9.31‐17.74, Lyon SMR = 7.22, 95%CI:4.13‐11.74). In a combined dataset of all patients from both cohorts, baseline FLIPI was no longer informative in EFS12 achievers. Reassessment of patient status at 12 months from diagnosis in follicular lymphoma patients, or at 24 months in patients treated with immunochemotherapy, is a strong predictor of subsequent overall survival in FL. Early event status provides a simple, clinically relevant endpoint for studies assessing outcome in FL. Am. J. Hematol. 91:1096–1101, 2016. © 2016 Wiley Periodicals, Inc.

Abstract Background: Copanlisib is a novel pan-Class I phosphatidylinositol-3-kinase (PI3K) inhibitor with potent preclinical inhibitory activity against both PI3K-δ and PI3K-α isoforms. A phase II study of copanlisib in patients with relapsed/refractory indolent or aggressive lymphoma reported promising activity in the indolent NHL group (Dreyling et al., ENA 2014). The objective of this study is to evaluate the efficacy and safety of copanlisib in patients with indolent B-cell NHL relapsed after or refractory to standard therapy. Methods: Patients meeting the following criteria are eligible for enrollment: histologically confirmed diagnosis of indolent B-cell NHL, with follicular lymphoma (FL) grade 1-2-3a, marginal zone lymphoma (MZL; splenic, nodal, or extra-nodal), small lymphocytic lymphoma (SLL) with absolute lymphocyte count &lt; 5 × 109/L at the time of diagnosis and at study entry, or lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM), and who have previously received ? 2 prior lines of therapy with rituximab and an alkylating agent and must be refractory to the last treatment with rituximab (refractory defined as progressing or not responding within 6 months of the last course of treatment). Patients will be randomized in 2:1 manner to receive 60 mg of copanlisib administered intravenously on days 1, 8 and 15 of a 28-day cycle or placebo administered on the same schedule until disease progression or intolerable toxicity. Patients in the placebo arm will be allowed to cross-over to receive follow-up treatment with copanlisib, after confirmed disease progression. Dose reductions due to toxicities will be allowed. Radiologic tumor assessment will be performed every 12, 16 or 24 weeks for years 1, 2, and 3, respectively. The primary endpoint will be progression-free survival (PFS). Secondary objectives include overall objective response rate (ORR), duration of response (DOR), time to progression (TTP), complete response rate (CRR), overall survival (OS), time to deterioration as well as time to improvement in disease-related symptoms. Exploratory objectives will include secondary PFS after first progression in placebo-treated patients who cross over to receive copanlisib and time to improvement and the time to deterioration in disease-related symptoms - physical (DRS-P) of at least 3 points as measured by the FLymSI-18 questionnaire. Approximately 189 patients who meet the eligibility criteria will be randomized 2:1, with approximately 126 patients in the copanlisib monotherapy arm and approximately 63 patients in placebo arm. The study is planned to detect a 132% increase in median PFS in copanlisib versus placebo (i.e. to detect a hazard ratio of 0.43), using a stratified log-rank test. This study is currently enrolling patients (NCT02369016). Citation Format: Grzegorz S. Nowakowski, Igor Gorbatchevsky, Florian Hiemeyer, Lisa Cupit, Barrett H. Childs. A randomized, double-blind phase III study of phosphatidylinositol-3 kinase alpha/delta inhibitor copanlisib versus placebo in patients with rituximab-refractory indolent non-Hodgkin's lymphoma (iNHL): CHRONOS-2. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT084.