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BACKGROUND Despite the impact of proteasome inhibitors and immunomodulatory agents, infusional chemotherapy regimens continue to be used for patients with multiple myeloma. To the authors' knowledge, contemporary data regarding salvage chemotherapy regimens are sparse, with no direct comparisons. METHODS The authors performed a single‐institution study comparing 3 salvage chemotherapy regimens in 107 patients with recurrent/refractory multiple myeloma: dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) in 52 patients; bortezomib, thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, and etoposide (VTD‐PACE) in 22 patients; and cyclophosphamide, vincristine, doxorubicin, and dexamethasone (CVAD) in 33 patients. RESULTS Differences between treatment groups existed, including higher baseline creatinine for patients treated with CVAD (P<.001) and greater prior use of infusional chemotherapy for those receiving VTD‐PACE (P<.001). There was no significant difference in response noted among the 3 regimens: 55% overall (P = .18). For the intent‐to‐transplant population, a similar percentage were successfully bridged to transplant without further therapy (62%; P = .9). There was no difference in survival observed across the 3 regimens, with an overall median progression‐free survival of 4.5 months (95% confidence interval, 3.6‐5.5 months [P = .8]) and a median overall survival of 8.5 months (95% confidence interval, 6.1‐11 months [P = .8]). Furthermore, there was no statistically significant difference noted among clinically relevant adverse events, although there was a suggestion of fewer adverse events with DCEP. Patients treated with the intent to transplant had superior outcomes for response (odds ratio, 3.40; P = .01), progression‐free survival (hazard ratio, 0.28; P<.001), and overall survival (hazard ratio, 0.19; P<.001). CONCLUSIONS The 3 salvage regimens demonstrated similar responses, survival, and adverse events. Given the short response durations observed in the recurrent/refractory disease setting, infusional chemotherapy is best suited for cytoreduction before more definitive therapy is administered. Cancer 2015;121:3622–3630. © 2015 American Cancer Society.

4973 Background/Rationale: Rituximab is an anti-CD-20 monoclonal antibody used in the management of lymphoproliferative disorders. Rituximab is indicated in maintenance therapy for follicular cell lymphoma and can be administered once every 2 months, once every 3 months, or weekly for 4 weeks every 6 months. The use of maintenance rituximab has improved progression free survival and overall survival in low grade follicular lymphomas. Although rapid rituximab infusions have been studied extensively, there is little data on the use of rapid infusions during maintenance therapy for low grade lymphomas. Herein we report our experience with rapid infusion rituximab in patients receiving maintenance therapy. Methods: All patients who received rapid infusion rituximab as maintenance therapy for low grade lymphoma between December 2007 and June 2011 were included. Patients were considered eligible for rapid infusions if they tolerated previous rituximab infusions and presented with a peripheral lymphocyte count of less than 4.8 k/μl. Rapid rituximab infusions were administered over 90 minutes (150 mL/hr for 30 minutes and then increased to 275 mL/hr until completion). Patients were monitored for signs and symptoms of reactions. In case of an infusion reaction supportive care medications were readily available. Demographic, laboratory and clinical data were collected. Adverse events were assessed through vital signs, symptoms of infusion related reaction and supportive care measures administered and graded according to the Common Terminology Criteria for Adverse Events Version 4. The primary and secondary objectives of this retrospective study were to evaluate the incidence of grade 3/4 and all grade infusion reactions with rapid rituximab infusions during maintenance therapy, respectively. Maintenance schedules were also compared with regards to incidence of infusion reactions. Results: A total of 105 patients received 629 rapid rituximab infusions. Patient demographics, laboratory, and clinical data are summarized in Table 1. All patients were eligible for rapid infusion rituximab according to institutional criteria. Two grade 2 infusion reactions and 4 grade 3 reactions were reported (1 patient experienced a grade 2 and 3 reaction); however none of these patients required hospitalization. All 5 patients received pharmacological and/or supportive care to relieve the symptoms associated with the reaction. Of these 5 patients, 3 patients went on to receive rapid infusions of rituximab; 2 patients were switched to standard infusion per physician request. The sample size was too small to determine if a correlation existed between infusion related reactions and the schedule of maintenance rituximab. Conclusion: The rapid infusion of rituximab in patients receiving maintenance therapy is well tolerated with minimal incidence of infusion-related reactions. Although the sample size was insufficient to assess differences in adverse effects according to the maintenance schedule, the low overall incidence of adverse effects suggests that rapid rituximab infusions are well tolerated regardless of maintenance schedule. Our study concludes rapid infusion rituximab is a safe and feasible option for maintenance therapy. Disclosures: Ho: Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees. Off Label Use: Maintenance Rituximab Therapy in Non-Hodgkin's Lymphoma. Cultrera:Genentech: Speakers Bureau. Sotomayor:Genentech: Membership on an entity's Board of Directors or advisory committees. Wetzstein:Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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BACKGROUND: The B-cell receptor (BCR) signaling pathway plays a pivotal pathogenic role in chronic lymphocytic leukemia (CLL). Ibrutinib is an irreversible Bruton's tyrosine kinase (BTK) inhibitor that effectively treats patients with CLL, including those harboring poor-risk mutations such as del17p. Here we present the outcomes of CLL patients (pts) who discontinued ibrutinib while being treated outside clinical trials. METHODS: The primary objective was to describe the clinical characteristics, reasons for of discontinuation and outcomes after stopping Ibrutinib. Using the Moffitt Cancer Center, Total Cancer Care and pharmacy registry, we identified and reviewed the charts of all CLL pts that had been treated with ibrutinib from January 2013 to July 2015. Pts were evaluated for time to discontinuation, reason for discontinuation and overall survival (OS) after discontinuation. Survival outcomes were estimated using the Kaplan-Meier method and the log-rank test. All analyses were done using SPSS version 19.0. RESULTS: We identified 54 relapsed/refractory (R/R) CLL pts treated with ibrutinib. The median age was 62 (36-80) and female/male ratio 0.1. The median number of prior therapies was 2 (1-6), 60% had unmutated IgVH, 36% had del17p and 14% had complex karyotype. Eighty percent received and failed fludarabine-based regimens (Table 1). After a median follow up of 9.1 months (0.5-23.3) for survivors, there were 22 (41%) CLL pts who discontinued ibrutinib; 7 due to disease progression (PD), 8 due to toxicity and 7 due to proceeding with hematopoietic stem cell transplantation (HSCT). The most common side effects that lead to ibrutinib discontinuation were: major bleeding events (3), atrial fibrillation (2), grade 3 constipation (1) and grade 2 recurrent skin rashes (1). The median duration of ibrutinib therapy was 3.7 (0.9 - 10.9) months. The median OS for CLL pts with PD after ibrutinib and HSCT was 5.5 and 10.8 months, respectively. In pts who discontinued ibrutinib due to toxicity, the median OS was not reached. Of the seven patients who underwent HSCT, 71% had unmutated IgVH, 43% had del17p, one had complex karyotype and all of them had a clinical response to ibrutinib (PR= 1 and SD =6) prior to HSCT. Four patients developed RichterÕs transformation (RT) upon progression with median OS of 3 months; 3 had del17p/complex karyotype. By univariate analysis RT was associated with inferior OS. CONCLUSION: R/R CLL patients that are treated with ibrutinib and experience disease progression have a dismal prognosis, especially in those who develop RT that appears to be the most important prognostic factor for OS in this group. In addition, ibrutinib appears to be an effective therapy for CLL pts as a bridge for allogeneic HSCT and in general for patients with R/R CLL. Table 1. Main characteristics of CLL patients that discontinued Ibrutinib outside clinical trials Patients characteristics Patients (N=22) Age at discontinuation* 62 (36-80) Unmutated IgVH 13 (60%) Del17p# 8 (36 %) Complex karyotype 3 (14%) Number of prior therapies* 2 (1-5) Clinical responseá Stable disease (SD)á Partial response (PR)á Progressive disease (PD) 12 (52%) 3 (13%) 2 (9%) *Median; #one patient had both del17p and TP53 mutation. Disclosures Shah: Acetylon: Membership on an entity's Board of Directors or advisory committees; Rosetta Genomics: Research Funding; Spectrum: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Honoraria; Pharmacyclics: Speakers Bureau; PLexus Communications: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics: Research Funding. Sokol:Spectrum: Consultancy; Seatle Genetics: Research Funding; Celgene: Consultancy. Pinilla-Ibarz:BMS: Consultancy, Honoraria, Other: Consulting & Advisory Role, Speakers Bureau; Pfizer: Consultancy, Other: Consulting & Advisory Role, Research Funding, Speakers Bureau; Novartis: Consultancy, Other: Consulting & Advisory Role, Research Funding; ARIAD Pharmaceuticals, Inc.: Consultancy, Other: Consulting & Advisory Role, Research Funding; Teva: Consultancy, Speakers Bureau.