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LBA7564 Background: Patients with r/r B-NHL have a dismal prognosis. DIAL (Dual Immunomodulation in Aggressive Lymphoma) was a multi-center randomized phase II study testing the efficacy of nivolumab (PD-1 inhibitor) plus varlilumab (CD27 agonist) in this population. Methods: Patients were randomized (1:1) to nivolumab (240 mg IV every 2 weeks for 4 months, 480 mg IV monthly thereafter; group 1) alone or combined with varlilumab (3 mg/kg IV monthly; group 2). Cross-over (group 1 to 2) was allowed for progression. Primary endpoint was overall response (ORR) per LYRIC criteria. A sample size of 48 patients per arm would provide 80% power to detect increase in ORR from 25% to 45% using a one-sided test (p = 0.15). Pre-specified interim analysis occurred after half of the patients completed first radiologic assessment. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Exploratory endpoints included tumor genomic assessment and immune profiling of blood and tumor. Results: 53 patients were enrolled (27 in group 1; 26 in group 2). Interim analysis included 24 patients from each arm. Mean age was 65.2 years, 34 (70.8%) were male, and 36 (75%) received prior CAR-T cell therapy. Baseline characteristics were balanced between arms. Grade ≥ 3 AEs were observed in 8 (33.3%) and 7 (30.4%) of patients in groups 1 and 2, respectively. Common AEs (> 5%) of any grade included fatigue, lymphopenia, diarrhea, rash. There were no treatment-associated deaths. Toxicity profile was similar between arms. Table summarizes efficacy outcomes. ORR was achieved in 6 patients (12.5%), not statistically different between arms; 4 responses were complete. Seven patients crossed over (1 responded after crossing). Median OS (8.6 vs 7.3 months; p = 0.39) and PFS (2.7 vs 1.4 months; p = 0.06) were similar between arms. Subgroup analysis of patients with prior CAR-T cell therapy showed similar ORR (5/36; 14%), not statistically different between arms. Correlative analysis results will be presented at conference. The trial met futility criterion on interim analysis and enrollment ceased based on pre-specified stopping rule. Conclusions: Dual immunomodulatory therapy did not enhance anti-tumor activity in patients with aggressive B-NHL compared to nivolumab alone. Response rates were low and consistent with previous data using PD-1 inhibitors in this population. Prior therapy with CAR-T cell does not seem to sensitize patients to PD-1 blockade. Toxicity profile was acceptable and dual therapy did not increase the rate of AEs. Clinical trial information: NCT03038672. [Table: see text]

e19562 Background: Considerable healthcare resource utilization and financial burden have been associated with the treatment of Waldenstrom Macroglobulinemia (WM); however, the impact of health insurance status on patient outcomes has not been explored. We aimed to assess the insurance-based outcome relationship in WM using the National Cancer Database (NCDB). Methods: We analyzed patient-level data obtained from the NCDB, a database representing more than 70% of newly diagnosed cancer cases nationwide. All newly diagnosed WM cases (n = 8540) between 2004 to 2017 were identified. Only patients who underwent treatment were included. Insurance status was recorded by assessing the primary payer at the time of diagnosis. Due to Medicare eligibility criteria, age-based (< 65 and ≥65 years) stratified analysis was conducted. Cox proportional hazards model was utilized to analyze survival. Time-to-event analysis was conducted based on date-of-diagnosis using the Kaplan-Meier method and log-rank test. Results: Analysis was conducted on 3878 patients after meeting inclusion criteria, with a median follow-up time of 54.6 months. Among patients < 65 years (n = 1249; median age: 58 years; male: 62.4%), those with non-private insurance had inferior survival on multivariate analysis (Table) after adjusting for patient demographics, comorbidities, income, education, treatment center characteristics, and treatment start time. Significant overall survival (OS) differences were seen in those < 65 years (log-rank p < 0.001), with 5-year OS highest among patients with private insurance 91.2%, compared to Medicaid 79.8%, uninsured 77.4%, and Medicare 70.2%. In patients < 65 years, compared to private insurance, uninsured patients were more likely to be of Black race, reside in lower income areas, and be treated at non-academic centers (all p < 0.05). Both Medicaid and Medicare patients < 65 years were more likely to have a higher Charlson-Deyo comorbidity index (> 1) and live in areas of lower educational attainment and household income compared to private insurance (all p < 0.05). In patients ≥65 years (n = 2629; median age: 75 years; 60.6% males), no insurance-based OS (log-rank p = 0.096) differences were seen. Conclusions: Based on our study, significant insurance-based disparities exist in WM, where patients < 65 years old who are uninsured, or non-privately insured are at a higher risk of mortality. While the root cause of these differences is not fully elucidated, efforts should focus on ensuring that all patients have equal access to care regardless of primary payer status.[Table: see text]

7530 Background: Clinical trials of novel salvage therapies (ST) have encouraging outcomes for relapsed/refractory classic Hodgkin lymphoma (R/R cHL) eligible for autologous stem cell transplant (ASCT). In this observational study, we report efficacies and outcomes of different ST in ASCT-eligible R/R cHL. Methods: Consecutive ASCT-eligible R/R cHL pts at 3 Mayo Clinic sites were included. Demographics and clinical variables at relapse were recorded by medical records review. Time to event endpoints were defined from relapse. Univariate associations were confirmed in multivariate models of age, sex, B symptoms, stage, bulky disease (BD, single mass > 6 cm) extra nodal disease (END), primary refractory disease (PRD) and early relapse (ER, within 1 year). Results: From Jan 2008 to May 2020, 207 ASCT-eligible pts with R/R cHL were included. Median age was 33 (24-43) years, 53% were male, 52% had advanced stage, 24% had BD, 36% had B symptoms, 41% had END, 11% had PRD and 43% had ER. All patients received ST and underwent ASCT; 43 (21%) received 2 ST, 14 (7%) 3 ST and 4 (0.5%) received 4 ST. 6 groups of ST were identified: ifosfamide, carboplatin and etoposide (ICE), bendamustine/brentuximab (BBV), brentuximab vedotin (BV), gemcitabine-based therapy (Gem), checkpoint inhibitor (CPI), and others. Table lists response to first line ST. BBV had significantly higher overall response rate (ORR) and complete response (CR) as first ST in univariate and multivariate models. 114 (79%) after ICE, 30 (97%) after BBV, 15 (56%) after BV, 25 (76%) after Gem, 8 (73%) after CPI and 15 (79%) after other ST underwent ASCT. Higher number of pts were bridged to ASCT after BBV than ICE (p95 0.2-0.8)) and higher number of ST was associated with lower OS (HR 2 (CI95 1.4-3)) in multivariate model (p95 1.2-3.5), p

Purpose Lenalidomide has significant single-agent activity in relapsed diffuse large B-cell lymphoma (DLBCL). We demonstrated that lenalidomide can be safely combined with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone); this new combination is known as R2CHOP. The goal of this phase II study was to evaluate the efficacy of this combination in newly diagnosed DLBCL. Patients and Methods Eligible patients were adults with newly diagnosed untreated stages II to IV CD20+ DLBCL. Patients received lenalidomide 25 mg orally per day on days 1 through 10 with standard-dose R-CHOP every 21 days for six cycles. All patients received pegfilgrastim on day 2 of each cycle and aspirin prophylaxis throughout. DLBCL molecular subtype was determined by tumor immunohistochemistry and classified as germinal center B-cell (GCB) versus non-GCB in the R2CHOP patients and 87 control patients with DLBCL from the Lymphoma Database who were treated with conventional R-CHOP. Results In all, 64 patients with DLBCL were enrolled, and 60 were evaluable for response. The overall response rate was 98% (59 of 60) with 80% (48 of 60) achieving complete response. Event-free survival and overall survival (OS) rates at 24 months were 59% (95% CI, 48% to 74%) and 78% (95% CI, 68% to 90%), respectively. In R-CHOP patients, 24-month progression-free survival (PFS) and OS were 28% versus 64% (P < .001) and 46% versus 78% (P < .001) in non-GCB DLBCL versus GCB DLBCL, respectively. In contrast, there was no difference in 24-month PFS or OS for R2CHOP patients on the basis of non-GCB and GCB subtype (60% v 59% [P = .83] and 83% v 75% [P = .61] at 2 years, respectively). Conclusion R2CHOP shows promising efficacy in DLBCL. The addition of lenalidomide appears to mitigate a negative impact of non-GCB phenotype on patient outcome.

e19557Background: The role of rituximab maintenance (RM) in mantle cell lymphoma (MCL) is unclear. Currently, rituximab is not an FDA approved therapy for this indication. We conducted a systematic...

Purpose Romidepsin (depsipeptide or FK228) is a member of a new class of antineoplastic agents active in T-cell lymphoma, the histone deacetylase inhibitors. On the basis of observed responses in a phase I trial, a phase II trial of romidepsin in patients with T-cell lymphoma was initiated. Patients and Methods The initial cohort was limited to patients with cutaneous T-cell lymphoma (CTCL), or subtypes mycosis fungoides or Sézary syndrome, who had received no more than two prior cytotoxic regimens. There were no limits on other types of therapy. Subsequently, the protocol was expanded to enroll patients who had received more than two prior cytotoxic regimens. Results Twenty-seven patients were enrolled onto the first cohort, and a total of 71 patients are included in this analysis. These patients had undergone a median of four prior treatments, and 62 patients (87%) had advanced-stage disease (stage IIB, n = 15; stage III, n= 6; or stage IV, n = 41). Toxicities included nausea, vomiting, fatigue, and transient thrombocytopenia and granulocytopenia. Pharmacokinetics were evaluated with the first administration of romidepsin. Complete responses were observed in four patients, and partial responses were observed in 20 patients for an overall response rate of 34% (95% CI, 23% to 46%). The median duration of response was 13.7 months. Conclusion The histone deacetylase inhibitor romidepsin has single-agent clinical activity with significant and durable responses in patients with CTCL.

Purpose Lenalidomide is a novel immunomodulatory agent with antiproliferative activities. Given its efficacy in a wide range of hematologic malignancies, we conducted a phase II trial (NHL-001) of single-agent lenalidomide in indolent non-Hodgkin's lymphoma (NHL). Patients and Methods Patients with relapsed/refractory indolent NHL were eligible, with no limit on the number of previous therapies. Oral lenalidomide 25 mg was self-administered once daily on days 1 to 21 of every 28-day cycle for up to 52 weeks as tolerated, or until disease progression. The primary end point was objective response rate (ORR), with secondary end points of duration of response (DR), progression-free survival (PFS), and safety. Results Forty-three enrolled patients were assessable for response and safety. Patients received a median of three prior systemic therapies (range, 1 to 17) and half were refractory to last therapy. ORR was 23% (10 of 43), including a 7% complete response (CR) or unconfirmed CR rate. Twenty-seven percent (six of 22) of patients with follicular lymphoma grade 1 or 2, and 22% (four of 18) with small lymphocytic lymphoma responded to therapy. Median DR was not reached, but was longer than 16.5 months with seven of 10 responses ongoing at 15 to 28 months. Median PFS for the whole group was 4.4 months (95% CI, 2.5 to 10.4 months). Adverse events were predictable and manageable; the most common grade 3 or 4 adverse events were neutropenia (30% and 16%, respectively) and thrombocytopenia (14% and 5%, respectively). Conclusion Oral lenalidomide monotherapy produces durable responses with manageable adverse events in patients with relapsed/refractory indolent NHL, warranting further investigation of treatment for indolent NHL.

7516 Background: PCNSL is a diffuse large B cell lymphoma confined to the CNS. Pomalidomide (POM) is a novel immunomodulatory agent with excellent CNS penetration (~40%) based on CNS PK analysis in rats and pre-clinical therapeutic activity against CNS lymphoma. Methods: A Phase I clinical trial was undertaken to determine the maximal tolerated dose (MTD) of POM, safety profile and overall response rate (ORR). Treatment consists of POM daily for 21 days every 28 days in combination with dexamethasone 40 mg PO weekly for two cycles followed by POM alone in subsequent cycles until progression or intolerance. 4 dose escalation levels of POM (3mg, 5mg, 7mg, and 10 mg) were planned. Thromboprophylaxis with oral anticoagulant or aspirin was required. MTD determination has been completed and expansion of the MTD cohort is ongoing. Therapeutic responses were evaluated per the international PCNSL collaborative group (IPCG) criteria after 2 cycles of treatment. The trial is registered with ClinicalTrials.gov (#NCT01722305). Results: 21 of 25 patients accrued were eligible for assessment. The MTD was determined to be 5 mg qd for 21 days every 28 days. Two DLTs were seen at dose level 3 (Grade 3 dyspnea and grade 4 thrombocytopenia). One DLT was seen in the expanded MTD cohort (Grade 4 neutropenia and lymphocytopenia). ORR for the study (9/21) was 43% (95% CI- 22%, 66%) with 4 CR, 1 CRu and 4 PR. 3 responders completed 2, 4, and 6 cycles before progression. 6 responders have completed 4, 5, 6, 10, 12, and 32 cycles and remain on treatment. ORR for the MTD dose level was (5/12) 42% (95% CI- 15%, 72%) with 3 CR and 2 PR. 2 patients had stable disease (SD). Pseudo-progression was seen in 1 patient. Overall, grade 3/4 toxicity was hematologic (neutropenia, anemia, and thrombocytopenia) in 38.1% and non-hematologic in 33.3% (fatigue, pneumonia, sepsis, syncope, dyspnea, hypoxia, respiratory failure and maculo-papular rash). Percent CSF/blood ratio of POM was determined to be 19% in 1 patient. Conclusions: Pomalidomide treatment is feasible with therapeutic activity against relapsed/refractory PCNSL and should be further developed. Clinical trial information: NCT01722305.

8520 Background: The non-germinal center B-cell like (non-GCB) subtype of diffuse large cell lymphoma (DLBCL) is associated with a worse outcome when treated with RCHOP chemotherapy. Lenalidomide h...

report a series of 55 patients with relapsed/refractory MM and their response to CYBORD. Methods: 55 patients with relapsed/refractory MM were treated with CYBORD on a 28 day cycle. Dosing was cyclophosphamide 300 mg/ m 2 PO once weekly; bortezomib 1 (2%), 1.3 (22%) or 1.5 mg/ m 2 (76%), IV (89%) or SQ (11%), once (87%) or twice weekly (13%); and dexamethasone 40 mg PO once weekly. We report response using the IMWG criteria 3 , and new onset neuropathy based on NCI CTCAE 4 . Results: Mean age was 65.6 years and 56% were male. Of the 55 patients, 64% had progressed while on therapy and 56% had a previous ASCT. Mean number of previous treatment lines was 3.3, and 36% and 82% were proteasome inhibitor (PI) and CYBORD naive. Median follow up time was 24.1 months and mean number of cycles was 5 (±4.4). ORR was 71%, 26% had ≥VGPR, and 13% CR. PI naive patients had an ORR of 95% while patients who had previously received a PI had an ORR of 57%. Median PFS and OS were 9.2 and 29 months, respectively. After a mean of 6 cycles, 22% of patients underwent subsequent ASCT. New onset grade 1 neuropathy was present in 16% of patients, while only 2% had grade 2 and none had grade 3 or greater neuropathy. We found an increase in PFS in PI naive patients (14.8 v 5.2 months, HR 0.4, 95%CI 0.2-0.7), patients that underwent a subsequent ASCT (19.7 v 6.3 months, HR 0.3, 95%CI 0.2-0.7) and patients that had ≤3 prior treatment lines (12 v 6.1 months, HR 0.5, 95%CI 0.2-0.8); no difference was found by mSMART 5 risk or prior ASCT. An increase in OS was found only in PI naive patients (35.4 v 21.2 months, HR 0.5, 95%CI: 0.3-0.98) and patients that underwent a subsequent ASCT (53.1 v 26.7 months, HR 0.3, 95%CI 0.2-0.8); no difference was found by number of previous treatment lines, mSMART risk or prior ASCT. Conclusions: CYBORD is an effective treatment regimen without significant increase in side effect profile for patients with relapsed/ refractory MM, achieving better outcomes in PI naive patients and those who undergo a subsequent ASCT, regardless of mSMART risk.

8514 Background: MLN9708 is an investigational, orally bioavailable, potent, reversible, specific inhibitor of the 20S proteasome that has demonstrated antitumor activity in in vivo models of MM. We report safety, activity and pharmacokinetics (PK) of weekly oral MLN9708 in a phase 1 trial in patients (pts) with relapsed and/or refractory MM after full enrollment (NCT00963820). Methods: Pts received MLN9708 (days 1, 8, 15; 28-day cycles) at 0.24–3.95 mg/m2 (dose-escalation phase) and at the MTD, 2.97 mg/m2, in relapsed and refractory (RR), bortezomib (btz)-relapsed, PI-naïve, and prior carfilzomib (CZ) expansion cohorts. Adverse events (AEs) were graded by NCI-CTCAE v3.0. Response was assessed by IMWG uniform criteria. Results: 60 pts (33 male, median age 64 yrs [40–79]) were enrolled, 32 in the dose-escalation phase and 31 to the expansion cohorts (11 RR, 10 btz-relapsed, 6 PI-naïve, 4 CZ; 2 RR and 1 btz-relapsed pts included from MTD dose-escalation cohort). Median time from MM diagnosis was 4.9 yrs (1.5–18.8). Median number of prior regimens was 6 (2–18), including btz, lenalidomide, thalidomide, and CZ in 83%, 95%, 52%, and 13%, respectively; 76% were refractory to last therapy (17% btz-refractory). At data cut-off (Nov 29, 2012) pts had received a median of 2 cycles (1–11); 5 pts remained on treatment. All-grade/grade ≥3 drug-related AEs were seen in 83%/52% of pts; common drug-related grade ≥3 AEs were thrombocytopenia (33%), diarrhea, neutropenia (17%), decreased appetite, fatigue, and lymphopenia (8%). 6 pts (10%) had drug-related PN (no grade ≥3). 5 pts discontinued due to drug-related AEs; 1 pt died on study due to an unrelated AE. By investigator assessment in 41 evaluable pts, responses included1 VGPR, 5 PR, 1 MR, and 15 with SD. MLN9708 was rapidly absorbed, with a terminal half-life of 4–12 days (supporting weekly dosing) and a proportional increase in plasma AUC with dose (0.8–3.95 mg/m2). PK data were similar across expansion cohorts. Conclusions: Current data suggest weekly oral MLN9708 is generally well tolerated with infrequent PN, and shows activity in this heavily pretreated population with prior exposure to immunomodulatory drugs and btz. Clinical trial information: NCT00963820.

8053 Background: Lenalidomide (LEN) is an immunomodulatory agent that has shown significant single-agent anti-lymphoma activity in patients with relapsed disease and in combination may enhance the efficacy of rituximab by various mechanisms. There is limited data on the role of LEN in combination regimens for treatment-naïve patients. This phase II single arm trial was designed to evaluate tumor response, toxicity (AE) and survival with a combination of LEN, rituximab, cyclophosphamide (CTX) and dexamethasone (DEX) (LR-CD) in symptomatic untreated patients with low grade B-cell non-Hodgkin lymphoma. Methods: Eligibility required age ≥18, ECOG PS ≤2, confirmed diagnosis of low-grade B-cell lymphoma (FL1-2, SLL, MZL or LPL/WM), measurable nodes ≥2cm or IgM ≥400mg/dL(LPL/WM), ANC ≥1400/mm3, platelets ≥100,000/mm3, creatinine ≤2mg/dL, signed informed consent and in need of therapy. Treatment consisted of IV rituximab 375mg/m2 D1, oral LEN 20mg D1-21, CTX 250mg/m2 D1, 8, 15, DEX 40mg D1, 8, 15, 22 and ASA 325 mg daily in a 28 day cycle. Treatment continued 2 cycles beyond best response (max 12). Toxicity was assessed by NCI CTCAE v3.0. Results: 28 patients have enrolled at Mayo Clinic with 25 evaluable for toxicity and 21 for response: Median age 65(43-83), 72% male, FL 24%, MZL 28%, LPL/WM 38%, and SLL 4%. Median number of cycles given was 5. Overall response in 21 patients with response data is 95% (95% CI 76-100%) with 19% CR (95% CI 5-42%), and 76% PR (confirmed and unconfirmed, 95% CI 53-92%). The ORR in 8 patients with LPL/WM with response data was 88%, all PR (95% CI 47-100%). At a median f/u of 14.7 months 96% are alive without progression. 1 death (unrelated) occurred 7.7 months after completing 12 cycles of treatment. The most common grade ≥3 AEs were neutropenia (37.5%), leukopenia (16.7%), anemia (12.5%) and fatigue (12.5%). Conclusions: The combination LR-CD with the novel agent LEN is feasible, well tolerated and produces high response rates in symptomatic patients with low grade B-cell NHL. Toxicities are manageable and similar to reported data of single agent LEN.

8034 Background: Phase 1 studies are evaluating IV and oral dosing of the reversible proteasome inhibitor MLN9708 in multiple tumor types. We report the safety, MTD, pharmacokinetics (PK), pharmacodynamics, and preliminary responses with weekly oral MLN9708 in pts with relapsed/refractory MM (NCT00963820). Methods: Pts aged ≥18 yrs received MLN9708 on d 1, 8, and 15 of 28-d cycles. In the dose-escalation phase, pts required ≥2 prior therapies (including bortezomib, thalidomide/lenalidomide, and corticosteroids). At the MTD, pts were to be enrolled to relapsed and refractory (RR), bortezomib-relapsed (VR), proteasome inhibitor (PI) naïve, and carfilzomib (CZ) expansion cohorts. Results: 36 pts have been enrolled to date (data cut-off: Dec 1, 2011), 32 in the dose-escalation phase (0.24–3.95 mg/m2) and 8 to expansion cohorts (2 RR, 5 VR, 1 PI naïve; RR and VR cohorts each include 2 pts from MTD dose-escalation cohort). Median age was 64.5 yrs (range 40–79), 53% were male, and median number of prior lines of therapy was 3.5 (range 1-13), including 92%, 92%, 56%, and 8% who had prior bortezomib, lenalidomide, thalidomide, and carfilzomib, respectively. Pts have received a median of 2 cycles (range 1–11); 5 pts remain on treatment. Among 24 DLT-evaluable pts, 3 DLTs were seen: 2 at 3.95 mg/m2 (1 grade 3 rash, 1 grade 3 GI AEs) and 1 at 2.97 mg/m2 (grade 3 GI AEs). The MTD was determined as 2.97 mg/m2. Overall, 69% of pts had drug-related AEs, and 28% had related grade ≥3 AEs, including thrombocytopenia (17%), diarrhea (11%), nausea, neutropenia, and fatigue (each 8%). Only 3 (8%) pts had drug-related peripheral neuropathy (PN; no grade ≥3). 2 pts discontinued due to AEs. In 18 response-evaluable pts, 1 had a VGPR at 3.95 mg/m2, 1 had a PR at 2.97 mg/m2, and 8 have achieved SD durable for up to 9.5 mos. PK analyses showed linear plasma PK (0.8–3.95 mg/m2), Tmax of 0.5-2 hr, and terminal half-life of 7 d for MLN2238 (biologically active hydrolysis product). There was a trend for a dose-dependent increase in whole blood 20S proteasome inhibition. Conclusions: Current data suggest weekly oral MLN9708 is generally well tolerated with infrequent PN, and shows early signs of antitumor activity.

8010 Background: Carfilzomib is a proteasome inhibitor that irreversibly binds its target with favorable toxicity profile that has shown significant activity in relapsed multiple myeloma (MM). Here we used carfilzomib as the center of a 4 drug induction regimen designed for MM patients pre stem cell transplant (SCT). Methods: We conducted a phase I safety run in 6 patients with no DLT observed before expanding to phase II. The phase II regimen is shown below. Treatment was for 4 cycles with expected SCT post induction. For the phase II portion of this trial, the primary endpoint is the proportion of patients who have ≥ very good partial response to treatment. All patients received herpes zoster prophylaxis and ASA daily. Results: Twenty seven patients were enrolled. Median age was 65 (range 27-74). ORR for evaluable patients (n=17) at phase II dosing is 100%: CR 35%, VGPR 48%, PR 18% after 4 cycles of CYCLONE. Grade 3 toxicity was reported in 52% of patients and 14% experienced a grade 4 toxicity. Grade 3/4 toxicities occurring in >5% of patients included fatigue, neutropenia, lymphopenia, thromboembolism, myopathy. Toxicities of any grade seen in >20% of patients included fatigue, constipation, lethargy, thrombocytopenia, somnolence, creatinine increased, malaise. Four patients (20%) developed grade 1 sensory neuropathy; no higher grade or painful neuropathy was evident. All patients are alive. All patients advancing to SCT successfully collected stem cells. One patient with t(4;14) disease who was not transplanted has progressed. 94% remain progression free. Conclusions: The 4 drug CYCLONE regimen has remarkable efficacy (83% ≥VGPR) and manageable toxicity in newly diagnosed patients with multiple myeloma. Especially notable was the low incidence of neuropathy and depth of response (CR 35%) after only 4 cycles. Given the relative lack of toxicity an extension of this regimen at higher doses of carfilzomib (20/45mg/m2) has been initiated. [Table: see text]

8043 Background: The mammalian target of rapamycin (mTOR) signal pathway controls cell proliferation and survival. The trial's goal was to determine the anti-tumor activity and safety of single-agent everolimus (TORC1 inhibitor) in patients with relapsed/refractory Waldenstrom macroglobulinemia (WM). Methods: Eligible patients had measurable disease (IgM monoclonal protein >1000 mg/dL with >10% marrow involvement or nodal masses >2 cm), a platelet count ≥75,000 x 106/L, a neutrophil count ≥1,000 x 106/L. Patients received everolimus 10 mg PO daily. Tumor response was assessed after cycles 2 and 6 and then every 3 cycles until progression. Results: 60 pts were treated. The median age was 64 years (range, 43-85). The median number of prior therapies was 3 (range, 1-11). All but two patients (97%) had received prior rituximab based therapy and 64% of patients had received prior alkylator based therapies. The overall response rate (complete response CR+ partial response PR+ minimal response MR) was 73% (95% CI: 60-84%), with a PR of 50% and 23% MR. The median time to progression (TTP), progression-free survival (PFS), and overall survival (OS) for the entire study population is 28 months (mos), (95% CI: 18-not reached (NR)), 22 mos (95% CI: 12 0-NR), and 55 mos (95% CI: 55-NR), respectively. The estimated PFS at 12 and 24 months is 62% (95%CI: 51-75%), and 48% (95%CI: 37-63%), respectively. The 30 patients who achieved a PR responded after a median of 2 months (range, 1-26) of treatment. The median duration of response (DR) for these patients has not yet been reached and 19 of these patients remain in response after a median follow up of 31 months (range, 3-54). All but two patients had a decrease in their serum IgM. Grade 3 or higher related toxicities were observed in 67% of patients. The most common were hematological toxicities with cytopenias. Pulmonary toxicity occurred in 5% of patients. Dose reductions due to toxicity occurred in 63% of patients. Conclusions: Everolimus has high single-agent activity with an overall response rate of 73% and manageable toxicity in patients with relapsed WM, and offers a potential new therapeutic strategy for this patient population.

8015 Background: Lenalidomide (Len) was demonstrated to have significant single agent activity in relapsed aggressive B cell lymphoma (J Clin Oncol. 2008;26:4952-7). However, the safety and efficac...

8037 Background: From time of diagnosis, patients with indolent lymphoma have a 10-year 30% risk of transformation to an aggressive non-Hodgkin's lymphoma (aNHL) (Al-Tourah. JCO. 2008). Patients wi...

8131 Background: Newly diagnosed MM patients (n = 150) were treated on 3 consecutive Phase II trials. Methods: RD (n = 34), CRD (n = 53) and CyborD (n = 63) were sequentially accrued (2004-2008) and analyzed for response and toxicity after 4 cycles of treatment and for progression free survival (PFS) and overall survival (OS) differences. Baseline parameters were balanced between trials except for ISS stage III (12%, 27% & 21% respectively). Median number of cycles delivered was higher for RD (8 vs. 5 vs. 4). Median age was 62 and 74 of the patients underwent stem cell transplantation. Risk profile by mSMART classification: high risk (N = 40) or standard risk (N = 89). Results: After 4 cycles of RD, CRD or CyborD, ≥ near complete response (nCR) was 13% vs. 2% vs. 47%, p

8025 Background: IMiDs propriety compounds have activity AL, an incurable plasma cell disorder related to multiple myeloma (MM). Pomalidomide (Pom), an IMiDs, is highly active and well-tolerated in MM. Methods: Persons with symptomatic, biopsy proved, previously treated, AL were eligible for IRB-approved treatment trial of Pom and dexamethasone (Dex). Subjects were required to have measurable hematologic disease, ECOG PS≥2, adequate hematologic reserve and creatinine ≤2.5 mg/dL, and ability to comply with contraceptive requirements. Pom (2 mg once daily) and Dex (40 mg once weekly) were given orally. Subjects received daily low-dose aspirin. Exclusion criteria were: active infection, thrombosis or cancer, NYHA classification >II, troponin T >0.1 ng/mL, ≥grade-3 peripheral neuropathy, or other AL therapy within 2 wks of enrollment. 34 subjects are to be enrolled. Between 11/24/08-11/23/09, 25 subjects enrolled. Results: Median age was 64 y (range 52 82); 19 were male. Median time from diagnosis to study-en...

8569 Introduction: Relapsed or refractory MCL patients demonstrated a promising overall response rate (ORR) of 53% with a median duration of response (DR) of 13.7 months to single-agent lenalidomide when analyzed as a subset in a recent a phase II study (NHL-002). A supporting international phase II trial (NHL-003) of single-agent lenalidomide was initiated for patients with relapsed or refractory aggressive NHL. In this report, we analyze the current results from the MCL patients enrolled in this trial. Methods: Patients with relapsed or refractory MCL and measurable disease 2 cm after at least 1 prior treatment regimen were eligible. Patients received 25 mg of lenalidomide orally once daily on days 1–21 of every 28-day cycle. Patients continued therapy until disease progression or toxicity. The 1999 IWLRC methodology was used to assess response and progression. Results: Fifty-four MCL patients were enrolled and were evaluable for response assessment. Median age was 69 years (33–82) and 40 patients (74%) were male. Median time from diagnosis was 3.2 years (0.4–10.4), patients had received a median of 3 prior treatments (1–8), 17 of the patients (32%) had received prior bortezomib therapy (MCL-bortezomib), and 14 (26%) had received a prior stem cell transplant (MCL-stem cell). Response rates are shown in the Table. The most common grade 3 or 4 adverse events were neutropenia (43%), thrombocytopenia (22%) and anemia (11%). Conclusions: This is the second study to demonstrate that lenalidomide oral monotherapy is effective in the treatment of patients with relapsed or refractory MCL, with manageable side effects. [Table: see text] [Table: see text]

8560 Background: Lenalidomide has shown activity in a wide range of hematological malignancies. We conducted a phase II trial of single-agent lenalidomide in indolent non-Hodgkin's lymphoma (NHL). Methods: Patients with relapsed or refractory indolent NHL were eligible, with no limit on the number of previous therapies. Oral lenalidomide 25 mg was self-administered once-daily on days 1–21 of every 28-day cycle for up to 52 weeks as tolerated, or until disease progression. The primary endpoint was overall response rate (ORR), with secondary endpoints of response duration, progression-free survival (PFS), and safety. Results: Forty-three patients were enrolled and were evaluable for response and safety. Patients had received a median of 3 prior systemic therapies (1–17) and half of all patients were refractory to their last therapy. The ORR was 23% (10/43), including a complete response (CR) or unconfirmed CR (CRu) rate of 7%. The median time to first response was 3.6 months (1.7–4.2) and the median time to CR or CRu was 4.2 months (1.9–11.1). Twenty-seven percent (6/22) of patients with follicular lymphoma grade 1 or 2, and 22% (4/18) of patients with small lymphocytic lymphoma responded to therapy. The median duration of response has not reached, but is longer than 16.5 months with 7 of 10 responses ongoing at 15–28 months. Median PFS was 4.4 months (2.5–10.4). Adverse events were consistent with the known safety profile of lenalidomide and manageable; the most common grade 3 or 4 adverse events were neutropenia (30% and 16%, respectively) and thrombocytopenia (14% and 5%, respectively). Conclusions: Oral lenalidomide monotherapy produces durable responses with manageable side effects in relapsed or refractory indolent NHL and warrants further investigation in the treatment of indolent NHL. [Table: see text]

8543 Background: Lenalidomide (len) with dexamethasone (dex) is increasingly used as induction therapy in newly diagnosed myeloma patients prior to transplant. We performed a retrospective chart re...

8573 Background: Small lymphocytic lymphoma (SLL) is an indolent B-cell neoplasm that is histologically and immunophenotypically identical to chronic lymphocytic leukemia (CLL), but has less periph...

8517 Background: The combination of oral cyclophosphamide, bortezomib and dexamethasone (CyBorD) is active in multiple myeloma (MM) producing rapid responses. The goal of this study was to determine the depth of that response in newly-diagnosed patients with multiple myeloma as assessed by CR, nCR and VGPR after 4 cycles of therapy. Methods: Patients with newly diagnosed MM were eligible if they had measurable or evaluable disease, were >18 years of age, had an ECOG PS

8509 Background: Lenalidomide is active with manageable side effects in non-Hodgkin’s lymphoma (NHL). This study aims to confirm the activity, safety, and predictors of response previously reported for lenalidomide in patients with relapsed/refractory (r/r) aggressive NHL in an international setting. Methods: Patients with r/r aggressive NHL with measurable disease (≥2 cm) after ≥1 prior treatment regimen were eligible. Patients received 25 mg lenalidomide orally once daily on Days 1- 21 every 28 days and continued therapy as tolerated or until disease progression. Response and progression were evaluated using the IWLRC methodology. Predictors of response were investigated by univariate analyses using Fisher’s exact test. Results: As of August 25, 2007, 46 patients were eligible for response assessment and 79 for safety evaluation. Median age was 65 (21–84) years, 74% were male, and 96% had received prior rituximab. Median time from diagnosis was 2 (0.2–12) years and median number of prior treatment regim...