ALBERT

Beschreibung: Introduction: APL, while highly curable in the modern era, remains a therapeutic challenge in the high-risk subset, with high rates of early mortality and relapse compared to non-high-risk APL. Recent evidence has confirmed excellent outcomes in non- high-risk APL with the combination of ATO and ATRA, and a previous pilot study had indicated the efficacy of a combination of ATO + ATRA + GO in high-risk APL. The North American Leukemia Intergroup designed a larger phase 2 study to confirm the efficacy and safety of this combination in high-risk APL. Primary Objectives: 1) assessment of 3-year event-free survival (EFS); 2) assessment of early (6 week) death rate. Methods: Adult patients with newly diagnosed high-risk APL (WBC ≥10k/uL) were eligible. Induction therapy consisted of: ATRA (45 mg/m2/day), beginning on day 1; ATO 0.15 mg/kg/day, beginning on day 10; GO 9 mg/m2on day 1. ATRA and ATO were continued until remission achieved. Patients in remission went on to receive consolidation with ATO x 2 cycles, followed by ATRA + daunorubicin x 2 cycles, followed by GO x 2 cycles. Subsequent maintenance therapy consisted of ATRA + 6-mercaptupurine + methotrexate for up to 1 year. Results: Between 2008 and 2013, 73 registered patients began protocol treatment. Median age was 46.5 years, with 52% females and 48% males. Sixty-two (85%) patients completed induction therapy as planned, and 50 patients (68%) completed all planned consolidation. Sixty-two patients (85%) achieved a documented complete response (CR). Non-responses were attributable to lack of response assessment (n=10), most commonly related to death. One patient had resistant disease. With a median follow-up of 3.3 years, the Kaplan Meier 3-year EFS estimate was 79% (95% CI 68% - 87%), which was significantly improved compared to the protocol-defined historical rate of 50% (p

Beschreibung: BACKGROUND: Chemoimmunotherapy for chronic lymphocytic leukemia (CLL) has been the standard of care for initial treatment. A randomized demonstrated both a progression free survival (PFS) and overall survival (OS) advantage when rituximab was added to fludarabine (F) and cyclophosphamide (C). Alemtuzumab (Campath) (CAM), an anti-CD52 monoclonal antibody, is an effective therapy for patients with both previously untreated and relapsed CLL. Its role in combination with chemotherapy is less certain. METHODS: We conducted a multicenter phase II clinical trial of FC followed by subcutaneous CAM in previously untreated CLL. Patients were eligible if they met standard criteria for initiating therapy, or if they were asymptomatic with the prognostically adverse immunoglobulin heavy chain variable (IGHV) gene unmutated status. Patients received fludarabine (25 mg/m2/day, days 1-3) and cyclophosphamide (250 mg/m2/day, days 1-3) every 28 days for six treatment cycles, followed by a 3-8 week rest period. Disease response was assessed, including minimal residual disease (MRD) status by sensitive flow cytometry in those in complete remission (CR). Patients who achieved less than a CR were eligible to receive standard dose CAM (30 mg thrice weekly for 12 weeks); those who were in CR but MRD positive could receive reduced dose CAM (30 mg weekly for 12 weeks). The primary outcome was duration of response (DOR). Secondary outcomes included the response rates after FC and after the addition of CAM, as well as the safety profile of the regimen. RESULTS: We enrolled 25 patients from November 2004 to June 2007 at 3 centers. The median age of the participants was 62 years (range 42-75). Detailed information was available for 17 patients pre-treatment: high risk Rai stage in 9, IGHV unmutated in 9 including 4 patients who were IGHV unmutated as their indication for treatment. Five patients had trisomy 12, 4 had 13q deletion, 1 each had 17p deletion and 11q deletion, and 6 had no abnormality. One patient was excluded from the analysis due to a diagnosis of mantle cell lymphoma after eligibility review. Four patients had no response evaluation and were considered treatment failures. Seventeen (71%) patients had a CR after 6 cycles of FC, including 11 who were MRD negative, one had a partial response (PR), and two had progressive disease (PD). Four of the 6 patients who were MRD positive received CAM after FC. Two required only a single dose to become MRD negative, and 2 received 12 weekly doses. One of these patients became MRD negative. The median DOR for those achieving CR was 38 months (range 12-105 months). There were no treatment related deaths. Five patients experienced a SAE including one with febrile neutropenia, two with pneumonia, and two with autoimmune hemolytic anemia. There were ten additional treatment emergent adverse events including two that were grade 3 (mucositis and fever) and one CMV reactivation while receiving CAM. Two patients developed treatment related myelodysplasia, one died and the other underwent allogeneic stem cell transplant. There were two deaths due to Richter’s transformation. During long term follow up, there have been five additional deaths. CONCLUSIONS: The CR rate after FC was higher than that reported in prior trials of previously untreated patients and the incidence of MRD negative CR was surprisingly high. The DOR was consistent with prior experience with FC. Too few patients received CAM to draw any conclusions about its role as a consolidative therapy given subcutaneously on a weekly schedule. Both the FC and CAM therapies were well tolerated, with few adverse events associated with their use. Disclosures No relevant conflicts of interest to declare.

Beschreibung: Introduction: PI3Kδ signaling is critical for the proliferation, survival and homing/tissue retention of malignant B cells. Idelalisib is a first-in-class, highly selective, oral inhibitor of PI3Kδ recently approved for the treatment of relapsed CLL in combination with R. This report summarizes the long-term follow-up of the Phase 1 combination experience of idelalisib with anti-CD20 antibodies. Methods: This Phase 1 study evaluated idelalisib for relapsed/refractory CLL continuously given at 100 mg BID (4 of the pts receiving R) or 150 mg BID (all other pts) in combination with a total of 8 infusions of rituximab (R, 375 mg/m2 weekly x 8), or a total of 12 infusions of ofatumumab (O, 300mg initial dose either on Day 1 or Day 2 relative to the first dose of idelalisib, then 1,000 mg weekly x 7, then 1,000 mg every 4 wks x 4). Pts on treatment after 48 weeks were eligible to continue idelalisib on an extension study. Clinical response was evaluated according to published criteria (Hallek 2008; Cheson 2012). Results: 40 pts (12F/28M) with a median (range) age of 66 (43-87) years and a WHO performance status of 0 (24, 60%) or 1 (16, 40%) were enrolled. 19 pts received idelalisib in combination with R and 21 with O. Adverse disease characteristics (n, %) included Rai Stage III/IV (20, 50%), bulky lymphadenopathy (23, 58%), refractory disease (15, 38%), multiple prior therapies (median 2, range: 1-9). Almost all pts (39, 98%) had at least 1 prior therapy containing R, and 3 of the 21 pts (14%) receiving idelalisib + O had received prior O. 63% of the pts receiving idelalisib + R, and 48% of the pts receiving idelalisib + O were refractory to R. Prior therapies also included alkylating agents (31, 78%, [bendamustine: 20, 50%]) and purine analogs (31, 78%, [fludarabine: 28, 70%]). Data available from 39 pts showed that 11 (28%) pts had evidence of del(17p) and/or TP53 mutations and 30 (75%) had unmutated IGHV. As of 7/15/2014, the median (range) treatment duration was 18 (0-44) months. 23 (58%) pts have completed the primary study and enrolled into the extension study. Primary reasons for study discontinuation (as reported by investigators) included disease progression (14, 35%), adverse events (AEs) (12, 30%), investigator request (3, 8%), withdrawal of consent (n=1), BMT (n=1). There were a total of 8 deaths on study: 2 deaths occurred after disease progression, and 6 pts died because of AEs (all assessed as unrelated/unlikely related to idelalisib by investigators). A total of 4 pts (10%) were continuing idelalisib treatment on the extension study at time of analysis. Selected treatment-emergent AEs (any Grade/≥Gr 3, regardless of causality) included diarrhea/colitis (55%/23%), cough (40%/3%), pyrexia (40%/3%), dyspnea (30%/3%), fatigue (25%/0%) nausea (25%/0%), rash (20%/0%), pneumonia (20%/18%), and pneumonitis (8%/5%). Elevation of liver transaminases (TA, any Grade/≥Gr 3) was seen in 30%/10%. Re-exposure to idelalisib after resolution of TA elevation generally was successful; only 1 patient discontinued the study because of (recurrent) TA elevation. Other AEs leading to study discontinuation and reported as possibly/probably related to idelalisib included diarrhea/colitis (4, 10%), pyrexia (n=1), interstitial lung disease (n=1), pneumonia (n=1), rash (n=1), psoriasis (n=1). Secondary malignancies leading to discontinuation (all reported as unrelated) were breast cancer (n=1), recurrent colon cancer (n=1), AML (n=1). There was no obvious overall difference in the toxicity reported for pts receiving idelalisib with rituximab compared to those with ofatumumab. The ORR (N=40) was 83% (33/40), with 2 CRs (5%) reported. Median PFS (N=40) and duration of response (DOR) (n=33) were 24 months. Median (range) time to response was 1.9 (range 1.7-16.9) months. Median overall survival (OS) has not been reached with a KM estimate for OS of 80% at 24 months. For the 11 pts with del(17p) and/or TP53 mutations, the response rate was 73%, and the median PFS and DOR were 20 and 24 months, respectively. Conclusions: Combinations of idelalisib with anti-CD20 antibodies such as R or O represent non-cytotoxic regimens with acceptable safety profiles and considerable activity resulting in durable tumor control in pts with relapsed/refractory CLL, including those with high risk factors such as del(17p) or TP53 mutations. A Phase 3 trial evaluating the efficacy of idelalisib in combination with ofatumumab is ongoing (NCT01659021). Disclosures Furman: Gilead Sciences: Research Funding. Off Label Use: Zydelig is a kinase inhibitor indicated for the treatment of patients with: 1) Relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities; 2) Relapsed follicular B-cell non-Hodgkin lymphoma (FL) in patients who have received at least two prior systemic therapies; and 3) Relapsed small lymphocytic lymphoma (SLL) in patients who have received at least two prior systemic therapies.. de Vos:Gilead Sciences: Research Funding. Barrientos:Gilead Sciences: Research Funding. Schreeder:Gilead Sciences: Research Funding. Flinn:Gilead Sciences: Research Funding. Sharman:Gilead Sciences: Research Funding. Boyd:Gilead Sciences: Research Funding. Fowler:Gilead Sciences: Research Funding. Leonard:Gilead Sciences: Research Funding. Rai:Gilead Sciences: Research Funding. Kim:Gilead Sciences: Employment, Equity Ownership. Viggiano:Gilead Sciences: Employment, Equity Ownership. Jahn:Gilead Sciences: Employment, Equity Ownership. Coutre:Gilead Sciences: Research Funding.

Beschreibung: Background: Ibrutinib (ibr), a first-in-class, once-daily, covalent, Bruton's tyrosine kinase inhibitor, is approved in the US for treatment of patients (pts) with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), including pts with del(17p). The activity and safety of ibr in this early phase pivotal study was investigated in pts receiving first line ibr and pts with relapsed/refractory (R/R) CLL/SLL. We report data on the longest follow up available, up to 7 y, for pts receiving single-agent ibr. Methods: Phase 1b/2 (PCYC-1102; NCT01105247) and extension study (PCYC-1103; NCT01109069) included pts receiving 420 mg (first line n=26; R/R n=67) or 840 mg QD ibr (first line n=5; R/R n=34) in the first line (≥65 y) or R/R (≥1 prior therapy) settings. Ibr was administered until disease progression (PD) or unacceptable toxicity. Efficacy was evaluated by investigator-assessed overall response rate (ORR, including partial response with lymphocytosis [PR-L]) using consensus criteria for CLL and SLL, duration of response (DOR; PR-L or better), progression free survival (PFS), and overall survival (OS). Responses were assessed for Döhner hierarchical subgroups. Median (95% CI) survival outcomes are reported. Adverse event (AE) monitoring was from first ibr dose until 30 days after the last dose; generally only grade ≥3 AEs and other significant AEs were collected on PCYC-1103. Results: Of 132 pts, 31 received first line ibr and 101 had R/R disease. As of the cutoff, 17 (55%) first line and 21 (21%) R/R pts continued ibr, with median (range) follow-up of 67 mo (0.7+, 87). Median (range) age for all pts was 68 y (37‒84); 43% of pts were ≥70 y (first line, 74%; R/R, 34%). Baseline genomic characteristics have been reported and included many high-risk features such as complex karyotype (first line, 13%; R/R, 37%) and unmutated IGHV (first line, 48%; R/R, 78%). R/R pts received a median (range) of 4 prior therapies (1‒12). ORR was 89% for all pts (complete response [CR], 15%), with similar rates in first line (87% [CR, 32%]) and R/R pts (89% [CR, 10%]). Median DOR was not reached (NR; 95% CI: not estimable [NE], NE) for first line and was 57 mo (38, 80) for R/R pts. Median PFS was NR (95% CI: NE, NE) for first line and was 51 mo (37, 70) for R/R pts (Fig 1); estimated 7 y PFS rates were 80% and 32%, respectively. Median OS was NR in first line (95% CI: 80, NE) or R/R pts (63, NE), with estimated 7 y OS rates of 75% and 52%, respectively. Median OS for pts with PD within 1, 3, and 5 y of treatment initiation was 13 (95% CI: 1, 25), 28 (17, 54), and 57 mo (28, NE), respectively. In R/R pts, median PFS was 26 mo (95% CI: 18, 37) in 34 pts with del(17p), 51 mo (31, 62) in 28 pts with del(11q), 82 mo (7, NE) in 5 pts with trisomy 12, and NR (63, NE) in 13 pts with del(13q). Median PFS was NR (95% CI: 40, NE) in 16 R/R pts with no abovementioned cytogenetic abnormalities. Among R/R pts, median PFS trended longer for 27 pts with 1‒2 prior lines of therapy (66 [95% CI: 37, NE]) versus 14 pts with 3 (59 [22, NE]) or 60 pts with ≥4 prior lines of therapy (39 [26, 51]). The primary reason for treatment discontinuation in first line pts was AEs (23%), whereas in R/R CLL it was PD (35%). Most common AEs (≥2 pts) leading to discontinuation were diarrhea, subdural hematoma, and sepsis (n=2 each). Grade ≥3 AEs were reported in 74% of first line and 89% of R/R pts, and serious AEs were reported in 61% of first line and 76% of R/R pts. Hypertension (first line, 32%; R/R, 26%) and pneumonia (first line, 10%; R/R, 27%) were among the most common grade ≥3 treatment-emergent AEs. A similar proportion of first line (10%) and R/R pts (9%) experienced major hemorrhage. Grade ≥3 atrial fibrillation (first line, 6%; R/R, 10%) and infection (first line, 23%; R/R, 55%) were more common in R/R pts. In all pts, grade ≥3 treatment-emergent AEs were highest during the first year of treatment and subsequently declined. Conclusions: With up to 7 y of follow-up, sustained activity of single-agent ibr was observed with first line ibr and for R/R pts with CLL/SLL, including those with high risk genomic factors. Responses were durable, with stable or improved CR rates, and sustained PFS and OS rates (estimated 7 y rates: 80% and 75% for first line pts and 32% and 52% in the highly pretreated R/R population, respectively). In R/R CLL, ibr administration in earlier lines of therapy resulted in improved PFS outcomes, with longer PFS after 1‒2 versus ≥3 prior lines of therapy. Ibr was acceptably tolerated, and most grade ≥3 AEs declined over time. Disclosures Furman: Loxo Oncology: Consultancy; Genentech: Consultancy; Verastem: Consultancy; Sunesis: Consultancy; Incyte: Consultancy, Other: DSMB; TG Therapeutics: Consultancy; Janssen: Consultancy; Gilead: Consultancy; AbbVie: Consultancy; Acerta: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy. Coutre:Beigene: Consultancy; Gilead: Research Funding; Pharmacyclics LLC, an AbbVie Company: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; AbbVie: Consultancy, Research Funding. Flinn:Janssen: Research Funding; Kite: Research Funding; Novartis: Research Funding; Agios: Research Funding; Merck: Research Funding; Calithera: Research Funding; Curis: Research Funding; Portola: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Pfizer: Research Funding; Seattle Genetics: Research Funding; Verastem: Consultancy, Research Funding; Incyte: Research Funding; Trillium: Research Funding; Pharmacyclics: Research Funding; Takeda: Research Funding; TG Therapeutics: Research Funding; ArQule: Research Funding; Forty Seven: Research Funding; Constellation: Research Funding; Celgene: Research Funding; Infinity: Research Funding; BeiGene: Research Funding; Verastem: Research Funding; Forma: Research Funding. Blum:Morphosys: Research Funding; Novartis: Research Funding; Seattle Genetics: Research Funding; Celgene: Research Funding. Sharman:Pharmacyclics, an AbbVie Company: Consultancy, Research Funding; Acerta: Consultancy, Research Funding. Wierda:Genentech: Research Funding; AbbVie, Inc: Research Funding. Luan:Pharmacyclics, LLC, an AbbVie Company: Employment; AbbVie: Equity Ownership. Liu:AbbVie: Equity Ownership; Pharmacyclics, an AbbVie Company: Employment, Other: TRAVEL, ACCOMMODATIONS, EXPENSES. Dean:CTI BioPharma Corp.: Employment, Equity Ownership; Pharmacyclics LLC, an AbbVie Company: Employment; AbbVie: Equity Ownership. O'Brien:Gilead: Consultancy, Research Funding; Regeneron: Research Funding; Sunesis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Celgene: Consultancy; Astellas: Consultancy; Aptose Biosciences Inc.: Consultancy; Abbvie: Consultancy; Pharmacyclics: Consultancy, Research Funding; Acerta: Research Funding; Janssen: Consultancy; TG Therapeutics: Consultancy, Research Funding; Amgen: Consultancy; Alexion: Consultancy; GlaxoSmithKline: Consultancy; Kite Pharma: Research Funding; Vaniam Group LLC: Consultancy.

Beschreibung: Key Points High WBC is an independent predictor of early HD in APL.

Beschreibung: Abstract 1015 Poster Board I-37 Background: Early mortality, mostly from hemorrhagic complications, occurs in less than 10% of patients currently treated in clinical trials for acute promyelocytic leukemia (APL). However, data about the proportion of patients developing such complications prior to clinical trial enrollment are scarce in the literature (Sanz M, et al Blood 2009). Approximately 5% of newly diagnosed patients with APL have been reported not to be eligible for participation in clinical trials due to very poor clinical condition, and their outcome has never been reported. However, enrollment on clinical trials may be difficult in specific clinical situations, such as after hours/weekend admissions and/or emergent requirement for therapy. This study reports the incidence, time of occurrence and clinical features of APL patients with a focus on early mortality. Methods: 150 consecutive APL patients treated at Stanford University between 8/1986 and 7/2009 were identified. Thirteen patients were excluded for lack of appropriate clinical information. Clinical features of patients with APL were analyzed for factors that might be relate to prognosis, including age, gender, white blood cell count, platelet count, fibrinogen, PTT, and INR. Continuous variables were compared with the t-test and categorical variables by Fisher's exact test or X-square statistic. The Kaplan–Meier method was applied to assess overall survival time. Results: Of the 137 patients included in this analysis, the median age at diagnosis was 45 (1-93) years and 78 (57%) were females. Using the PETHEMA criteria, there were 37, 46 and 20 patients with high-, intermediate- and low-risk disease (34 patients could not be classified based on partial/missing data). With a median follow-up time of 748 (0-6,235) days for the entire cohort, 52 (38%) have died. 19 (14%) and 11 (8%) of these patients died within 7 and 3 days of presentation, respectively. Patients with high-risk features had a 13% and 24% chance of dying with 3 and 7 days of presentation, respectively, with significantly inferior outcomes (p=0.045) when compared to those with intermediate-risk patients (6% and 13%) and low-risk disease (5% and 5%). Patients with unknown risk category faired similarly to low-risk patients. The most common cause of early mortality in these 19 patients was intracranial hemorrhage (n=11). Patients with early death (ED) (either

Beschreibung: Key Points Our 5-year experience shows sustained single-agent efficacy of ibrutinib in CLL patients, with complete response rates increasing over time. Long-term ibrutinib was well tolerated with no new safety signals; rates of grade ≥3 cytopenias decreased with continued therapy.

Beschreibung: Introduction: The overall outcome of patients (pts) with chronic lymphocytic leukemia (CLL) who relapse after or become refractory to treatment with B-cell receptor (BCR) signaling antagonists, including ibrutinib (IBR) or idelalisib (IDE), is recently being appreciated and appears quite poor. To date, no phase 2 studies have reported efficacy in this population. Venetoclax is a selective, potent, orally bioavailable BCL-2 inhibitor with a BCR-independent mechanism of action and substantial activity in pts with heavily pretreated relapsed or refractory CLL. We report preliminary results from an ongoing phase 2, open-label study evaluating venetoclax monotherapy in CLL pts relapsed after or refractory to IBR or IDE (NCT02141282). Methods: Pts with CLL relapsed after or refractory to IBR (Arm A) or IDE (Arm B) receive venetoclax monotherapy starting at 20 mg followed by a 5-step weekly ramp-up to a final daily dose of 400 mg. Pts with Richter's transformation (RT) suspected by screening PET CT or confirmed by lymph node biopsy are ineligible. The primary objectives are to assess the efficacy (investigator assessed overall response rate, ORR) and safety of venetoclax. Disease and response assessment was performed using iwCLL criteria at weeks 8, 24 and every 12 weeks thereafter. Adverse events (AEs) are monitored throughout the study. Results: As of April 30, 2015, 28 pts were enrolled in the study. Three screened pts were ineligible due to RT. Pt demographics are summarized by treatment arm in the table. Twenty-two entered into Arm A after a median duration on IBR of 15.5 months (range: 1-56). Investigator-reported best responses while on IBR prior to starting venetoclax were 14 partial response (PR), 4 stable disease (SD) and 3 progressive disease (PD); best response for 1 pt is unknown. Six entered into Arm B after a median duration on IDE of 9.7 months (range: 1-34). Investigator-reported best responses while on IDE prior to starting venetoclax were 1 complete response (CR), 3 PR and 2 SD. At last follow-up, the median time on venetoclax was 2.4 months (range: 0.1- 7) for Arm A and 1.7 months (range: 1.2-4.5) for Arm B. Venetoclax discontinuation occurred in 4 pts in Arm A (1 each due to respiratory failure, multi-organ failure, PD of RT, death of unknown cause) and in 1 pt in Arm B (PD prior to first assessment). Fifteen pts in Arm A and 3 in Arm B underwent Week 8 response assessment. In Arm A, 8/15 (53%) achieved a PR, 6/15 (40%) had SD, and 1/15 was inevaluable. In Arm B, 2/4 achieved a PR, 1/4 had SD, and 1/4 had PD prior to first assessment. Pts with SD had evidence of ongoing disease reduction, measured by decreasing circulating lymphocytes and lymph nodes. As of the cutoff date, 23 pts remain on venetoclax therapy. Compared to prior venetoclax monotherapy studies, no new safety signals for venetoclax were observed in either treatment arm. Treatment-emergent AEs (all grades) in 〉25% of the overall population were neutropenia (57%), anemia (35%), diarrhea (32%) and nausea (32%). Treatment-emergent grade 3/4 AEs in 〉10% of the overall population were neutropenia (43%; 3/12 of the neutropenic pts developed febrile neutropenia), anemia (29%), thrombocytopenia (18%), hypophosphatemia, hypoxia, leukopenia, and pneumonia (each 11%). Serious AEs in ≥2 pts overall were febrile neutropenia, increased blood potassium, multi-organ failure, and pneumonia (each 7%). Prior to study entry, 7/22 (32%) in Arm A received G-CSF support. One pt with high disease burden developed laboratory TLS in week 4, upon escalating to the 200 mg daily venetoclax dose, evident by hyperuricemia and hyperphosphatemia. Electrolytes returned to normal levels after a dose interruption and intervention. No pts experienced clinical TLS; laboratory changes were not clinically significant. Conclusions: In this group of pts with aggressive disease relapsed after or refractory to BCR-targeted agents, venetoclax monotherapy demonstrated early activity at the 8 week assessment, which occurred within 3 weeks of reaching the target 400 mg daily dose. The majority of evaluable pts achieved PR or SD. Venetoclax monotherapy exhibited a tolerable safety profile without events of clinical TLS. This is the first phase 2 study to show activity in a relatively uniform population of pts previously treated with BCR kinase inhibitors; the data suggests that venetoclax is active in these pts. Enrollment in both arms was ongoing as of the data cut. Figure 1. Figure 1. Disclosures Jones: Genentech, Pharmacyclics; institutional research funding from Abbvie, Pharmacyclics, Genentech, and Gilead: Other: Advisory Board. Off Label Use: Venetoclax is an investigational drug that is not yet approved in this indication.. Mato:AbbVie: Consultancy, Research Funding; Genentech: Consultancy; Pharmacyclics: Consultancy, Research Funding; Pronai Pharmaceuticals: Research Funding; Celgene Corporation: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; TG Therapeutics: Research Funding. Coutre:AbbVie: Research Funding. Wierda:Genentech: Consultancy; AbbVie and Genentech: Research Funding. Choi:AbbVie and Gilead: Membership on an entity's Board of Directors or advisory committees; Gilead: Speakers Bureau; AbbVie: Research Funding. Davids:AbbVie and Janssen: Consultancy; Genentech and Infinity Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics, TG Therapeutics, and Infinity: Research Funding. Lamanna:Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding. Barr:Pharmacyclics: Research Funding; AbbVie and Pharmacyclics: Consultancy. Burns:AbbVie: Employment, Equity Ownership. Montalvo:AbbVie: Employment, Equity Ownership. Zhu:AbbVie: Employment, Equity Ownership. Busman:AbbVie: Employment, Equity Ownership. Potluri:AbbVie: Employment, Equity Ownership. Humerickhouse:AbbVie: Employment, Equity Ownership. Byrd:Pharmacyclics: Research Funding; Genenttech, AbbVie, Acerta, Pharmacyclics: Other: Unpaid consultant.

Beschreibung: Background: Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) occurs primarily in older patients (pts) who often have increased comorbidities and cannot tolerate aggressive treatments, which leads to poorer outcomes (Balducci, Cancer Control 2015; Thurmes, Leuk Lymphoma 2008). Alkylating agents, such as chlorambucil (clb), have been commonly used to treat these pts (Eichhorst, Blood 2009). Ibrutinib (ibr), a first-in-class, once-daily, inhibitor of Bruton's tyrosine kinase, is indicated by the US FDA for the treatment of pts with CLL/SLL and allows for treatment without chemotherapy. RESONATE-2 (PCYC-1115) is a randomized phase 3 trial designed to compare the efficacy and safety of ibr vs clb in pts with treatment-naïve (TN) CLL/SLL (Tedeschi, ASH 2015). Primary results, as assessed by an independent review committee (IRC), demonstrated with a median follow-up of 18.4 mo that ibr significantly reduced the risk of progression or death by 84% (P