Chihara, Dai

7573 Background: While most patients (pts) with follicular lymphoma (FL) usually have favorable outcomes, those with refractory disease after first-line anti-CD20 based immunochemotherapy (IC), or progression within 24 months of diagnosis (POD24) have higher risk of premature death. There are no standard approaches for treating this vulnerable group and studies testing novel agents are ongoing in this setting. We sought to investigate clinical practice treatment choices and efficacy for pts with POD24 that align with eligibility criteria for the randomized SWOG1608 which compares IC with novel agents in this population. Methods: This was a multicenter observational cohort study from the LEO Consortium. Eligible pts had grade 1-3a FL diagnosed between 1/1/2002 and 2/1/2019, and initiated therapy after POD24 to first-line bendamustine or CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) based IC. Observation, radiotherapy, or rituximab monotherapy were permitted prior to IC and pts with transformation prior to the subsequent therapy after IC were excluded as per S1608. Outcomes of interest were overall and complete response rate (ORR/CR), progression-free survival (PFS), and overall survival (OS). Results: We identified 196 eligible pts with early progression to IC (39% antiCD20 Benda; 61% antiCD20 CHOP) who received subsequent therapy. Median age at post IC treatment was 57 years, 78% grade 1-2 FL. Treatments for pts with POD24 included CHOP- or Benda-based in 31%, salvage/hematopoietic stem cell transplant (HSCT) in 27%, novel therapies in 10% (including phosphatidylinositol 3-kinase inhibitors), antiCD20 monotherapy in 9%, and lenalidomide-based treatment in 8% (table); 21% of pts were treated on clinical trials. Across all treatments, ORR (CR) was 63% (37%) (95% CI: 55-70). At a median follow up of 6.2 years, 2 year PFS was 22% (95% CI: 17%-29%) and 5 year OS was 71% (95% CI: 65-79). Outcomes by regimen are shown in the table. Conclusions: Pts with FL experiencing POD24 following first-line IC are treated heterogeneously, with many pts still receiving IC as subsequent therapy. Despite modest CR rates and low 2-year PFS, 5-year OS appear to be improving compared to historical outcomes. This supports the ongoing need to investigate novel treatments in this population. [Table: see text]

Abstract Hairy cell leukemia (HCL) is a rare B-cell malignancy, and there is a need for novel treatments for patients who do not benefit from purine analogs. Ibrutinib, an oral agent targeting Bruton tyrosine kinase in the B-cell receptor signaling pathway, is highly effective in several malignancies. Its activity in HCL was unknown, so we conducted a multisite phase 2 study of oral ibrutinib in patients with either relapsed classic or variant hairy cell leukemia. The primary outcome measure was the overall response rate (ORR) at 32 weeks, and we also assessed response at 48 weeks and best response during treatment. Key secondary objectives were characterization of toxicity and determination of progression-free survival (PFS) and overall survival (OS). Thirty-seven patients were enrolled at 2 different doses (24 at 420 mg, 13 at 840 mg). The median duration of follow-up was 3.5 years (range, 0-5.9 years). The ORR at 32 weeks was 24%, which increased to 36% at 48 weeks. The best ORR was 54%. The estimated 36-month PFS was 73% and OS was 85%. The most frequent adverse events were diarrhea (59%), fatigue (54%), myalgia (54%), and nausea (51%). Hematologic adverse events were common: anemia (43%), thrombocytopenia (41%), and neutropenia (35%). Ibrutinib can be safely administered to patients with HCL with objective responses and results in prolonged disease control. Although the initial primary outcome objective of the study was not met, the observation of objective responses in heavily pretreated patients coupled with a favorable PFS suggests that ibrutinib may be beneficial in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01841723.

Background: Obesity is increasing worldwide, with the highest prevalence in the United States. High or low body mass index (BMI) is a well-established risk factor for increased all-cause mortality and also has been associated with cancer-specific mortality. However, the impact of BMI on survival following diagnosis with lymphoma currently remains controversial. We leveraged a prospective cohort of lymphoma patients to assess the relationship of BMI two years prior to diagnosis (BMI-2), at diagnosis (BMI-dx), and three-years post-diagnosis (BMI+3) with lymphoma-specific survival (LSS) as the primary endpoint and with event-free survival (EFS) and overall survival (OS) as secondary endpoints. Patient and Method: Patients were prospectively enrolled at lymphoma diagnosis to the SPORE Molecular Epidemiology Resource (MER) cohort at Mayo Clinic and University of Iowa from 2002-2015. BMI-2 and BMI+3 were self-reported in patient questionnaires, while BMI-dx was extracted from the medical chart. Patients with extreme BMI (BMI <14 and BMI ≥50) were excluded from the analysis. BMI change from BMI-2 to BMI-dx and from BMI-dx to BMI+3 was categorized as no change (-5% to 5%), decrease (>-5%), and increase (>+5%). Person-time at risk was assessed from lymphoma diagnosis until death or last follow-up, except for analyses of BMI change from BMI-dx to BMI+3, which started person-time at risk when the 3-year (+/- 6 months) follow-up questionnaire was returned. Cause of death was assigned by a study clinician. For all lymphoma patients combined and in the most common subtypes, we evaluated the association of BMI at each time point and change in BMI with EFS, LSS, and OS using hazard ratios (HRs) and 95% confidence intervals (CI) from multivariable adjusted Cox models. Results: A total of 4,009 lymphoma patients (including 670 diffuse large B-cell lymphoma [DLBCL], 689 follicular lymphoma [FL] and 1018 chronic lymphocytic leukemia/small lymphocytic lymphoma [CLL/SLL] and 1,632 others) with data on BMI-dx were included. Among them, 2,955 patients had BMI-2 and 2,004 had BMI+3 and were evaluable for change in BMI. The median age of all patients at diagnosis was 61 years (range 18-92 years), and 94% of patients had ECOG performance status <2. At the time of diagnosis, 28% were normal weight (BMI 18.5-25), 1% were underweight (BMI <18.5), 39% were overweight (BMI 25-30) and 32% were obese (BMI ≥30). With a median follow-up of 108 months from diagnosis (IQR 83-143 months), 1320 deaths were observed, 48% of which were due to lymphoma. Patients with FL who were obese at BMI-2 had significantly shorter LSS (HR: 3.02, 95%CI: 1.43-6.41, p=0.004). Associations between obesity at BMI-2 and LSS were not evident for DLBCL (HR: 1.04, 95%CI: 0.62-1.76, p=0.879) or CLL/SLL (HR: 1.10, 95%CI: 0.71-1.70, p=0.668) (Table). BMI-dx was not associated with LSS in any lymphoma patients, except that DLBCL patients who were underweight at BMI-dx (n=10) experienced shorter LSS (HR: 3.52, 95%CI: 1.22-10.1, p=0.020). This correlated significantly with presence of B symptoms (p=0.004) and may signify aggressive disease. Across all subtypes, >5% decrease in BMI from BMI-2 to BMI-dx was associated with significantly shorter LSS in patients with (HR: 2.02, 95%CI: 1.65-2.48, p<0.001). However, only for FL patients, >5% increase in BMI from BMI-dx to BMI+3 also was associated with significantly shorter LSS in subsequent years (HR: 3.74, 95%CI: 1.30-10.8, p=0.014). The associations reported for LSS generally were similar for EFS and OS. Conclusions: FL patients with obesity prior to diagnosis or who experienced increasing BMI after the diagnosis had significantly shorter LSS. The impact of weight control after the diagnosis of FL patient outcomes warrants investigation. Figure Disclosures Maurer: Celgene / BMS: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Nanostring: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees. Flowers:Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; Denovo Biopharma: Consultancy; Celgene: Consultancy, Research Funding; BeiGene: Consultancy; Kite: Research Funding; Bayer: Consultancy; Eastern Cooperative Oncology Group: Research Funding; Cancer Prevention and Research Institute of Texas: Research Funding; National Cancer Institute: Research Funding; AbbVie: Consultancy, Research Funding; V Foundation: Research Funding; TG Therapeutics: Research Funding; Burroughs Wellcome Fund: Research Funding; Millennium/Takeda: Consultancy, Research Funding; Acerta: Research Funding; Spectrum: Consultancy; Pharmacyclics/Janssen: Consultancy; Karyopharm: Consultancy; OptumRx: Consultancy; Gilead: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding. Cerhan:NanoString: Research Funding; BMS/Celgene: Research Funding.