Safety Of Ibrutinib In Patients Research Articles

Final results on effectiveness and safety of Ibrutinib in patients with chronic lymphocytic leukemia from the non-interventional FIRE study.

We conducted an observational study (FIRE) to understand the effectiveness and safety outcomes of ibrutinib in patients with chronic lymphocytic leukemia (CLL) in France, after a maximum follow-up of five years. Patients were included according to the French marketing authorization in 2016 (i.e. patients with relapsed or refractory CLL or to previously untreated CLL patients with deletion 17p and/or tumor protein p53 mutations unsuitable for chemoimmunotherapy) and could have initiated ibrutinib more than 30days prior their enrolment in the study (i.e. retrospective patients) or between 30days before and 14days after their enrolment (i.e. prospective patients). The results showed that in the effectiveness population (N = 388), the median progression-free survival (PFS) was 53.1 (95% CI: 44.5-60.5) months for retrospective patients and 52.9 (95% CI: 40.3-60.6) months for prospective patients and no difference was shown between the PFS of patients who had at least one dose reduction versus the PFS of patients without dose reduction (p = 0.7971 for retrospective and p = 0.3163 for prospective patients). For both retrospective and prospective patients, the median overall survival was not reached. The most frequent treatment-emergent adverse event of interest was infections (57.6% retrospective; 71.4% prospective). A total of 14.6% of the retrospective patients and 22.4% of the prospective patients had an adverse event leading to death. Our findings on effectiveness were consistent with other studies and the fact that patients with dose reductions had similar PFS than patients without dose reduction is reassuring. No additional safety concerns than those already mentioned in previous studies could be noticed.Trial registrationClinicalTrials.gov, NCT03425591. Registered 1 February 2018 - Retrospectively registered.

Outcomes with ibrutinib in patients with chronic lymphocytic leukaemia: Results from the German multicentre REALITY study.

To assess treatment adherence, effectiveness and safety outcomes of patients with chronic lymphocytic leukaemia (CLL) receiving ibrutinib in a real-world setting. Patients enrolled in REALITY were ≥18 years with a confirmed diagnosis of CLL and were receiving ibrutinib as a first-line (1L), 2L or ≥3L therapy. Treatment retention, adherence, progression-free survival (PFS), overall survival (OS) and time to next therapy were assessed at 1 and 2 years overall, by typology and by cytogenetic subgroups. PFS and OS were analysed using Kaplan-Meier methods. Exactly 302 patients were enrolled across 57 sites in Germany, from January 2017 to July 2021. One-year retention rates were 69.9% overall (primary endpoint), 77.9% for 1L patients, and 77.6%/78.8% for high-risk patients with del17p/TP53. At 2 years, PFS/OS rates were 77.8%/90.7% overall (1L, 82.7%/90.4%), and were consistent across cytogenetic subgroups. PFS rates were higher for 1L versus ≥3L patients. Patients with the low-acceptance/low-control typology at baseline were less likely to retain treatment at 1 year versus the high-acceptance/high-control typology. No new safety signals were observed. The REALITY study provides further evidence of the effectiveness and safety of ibrutinib in patients with CLL in a real-world setting, particularly in earlier treatment lines.

Real-World Effectiveness and Safety of Ibrutinib in Patients with Chronic Lymphocytic Leukemia (CLL) in Belgium after 4 Years

Background: The Belgian ibrutinib Real-world Data (BiRD) study is a multicenter, non-interventional, observational cohort study of adults with confirmed CLL, mantle cell lymphoma, or Waldenström's macroglobulinemia. Aim: To assess the effectiveness and safety of ibrutinib treatment of CLL in routine clinical practice in Belgium. Methods: Eligible patients initiated reimbursed ibrutinib treatment upon or after commercial availability in Belgium (August 1, 2015) or participated in the Medical Need Program and switched to reimbursed ibrutinib with commercial availability. The primary outcome measures were progression-free survival (PFS) and overall response rate (ORR); secondary outcome measures included overall survival (OS) and safety. Data were collected both prospectively (pro) and retrospectively (ret). Pro-collected adverse events (AEs) included all treatment-emergent AEs (TEAEs), whereas ret-collected AEs included only those considered related to ibrutinib; therefore, TEAEs for the pro group and AEs for the ret group are reported separately. To account for patients who could not be included in the ret group as they died before study entry and were therefore unable to provide consent, total population effectiveness results were adjusted with left truncation. We report results from the fourth interim analysis (cutoff: August 20, 2022) for patients with CLL, with a median follow-up of 49.1 months. Results: The effectiveness population included 221 patients (pro, n = 71; ret, n = 150). Median age at ibrutinib initiation was 72 years (range, 38-90); 64.3% were male; median time from diagnosis to ibrutinib initiation was 5.8 years (range, 0-31.4). Del17p/ TP53 mutation was present in 78/132 (59.1%) patients; 22/80 (27.5%) were IGHV-mutated. Nearly one-third of patients (27.4%) were treated first line, 24.2% received 1 prior line of therapy (LOT), 27.9% received 2 prior LOTs, and 20.5% received ≥ 3 LOTs. A history of significant cardiovascular disease was reported by 17.8% patients. Ibrutinib was initiated at 420 mg/day in 88.1% of patients, and 91 (40.3%) patients had ≥ 1 dose modification. Among these patients, who may have had more than 1 modification (increase or decrease), the most common reasons for dose modification were physician preference (59.3%) and toxicity (45.1%). Of the total 226 patients, 58 (25.7%) had ≥ 1 dose increase and 89 (39.4%) had ≥ 1 dose decrease. With ibrutinib treatment, median PFS was 46.0 months in the overall CLL population (Figure), and 49.1/53.6 months in the pro/ret groups. ORR was 90.9% (CR 21.7%, PR 53.4%, PR with lymphocytosis 15.8%). Median OS was 62.3 months (not estimable/91.0 months in pro/ret). Main effectiveness outcomes stratified according to age, prior LOT, and mutation status are listed in the Table. The safety population included 226 patients (pro, n = 73; ret, n = 153). TEAEs/AEs and serious TEAEs/AEs were reported in 100.0/85.6% and 69.9/50.3% in the pro/ret groups, respectively. TEAEs/AEs led to dose reduction, interruption, or withdrawal in 24.7/13.7%, 45.2/28.8%, or 30.1/21.6% of patients in the pro/ret groups, respectively. TEAEs/AEs of interest in the pro/ret groups were major bleeding (5.5/2.6%), infection (76.7/65.4%), hypertension (17.8/11.8%), atrial fibrillation (13.7/9.2%), arthralgia/myalgia (27.4/11.1%), diarrhea (24.7/13.7%), and rash (16.4/9.8%). Ibrutinib was permanently discontinued in 164 (72.6%) patients, most commonly due to disease progression (n = 40). The median duration of treatment was 35.8 months; 32 of the 226 patients discontinued ibrutinib due to toxicity (14.2%), and 27.4% of patients remain on treatment. Conclusions: In this Belgian real-world study, ibrutinib was found to be an effective treatment for patients with CLL, including those with higher risk mutations, several prior LOTs, and older age, with first-line patients who joined the study later responding particularly well. These findings are consistent with those from clinical trials, which support more effective outcomes for ibrutinib when utilized in the frontline (eg, RESONATE-2: Barr PM, et al. Blood Adv. 2022;6:440-3450; RESONATE: Munir T, et al. Am J Hematol. 2019;94:1353-1363). TEAEs/AEs are consistent with the known safety profile of ibrutinib.

Long-term Use of Ibrutinib in Japanese Patients with Steroid Dependent/Refractory cGVHD: Final Analysis of Multicenter Study.

Chronic graft-versus-host disease (cGVHD) is a serious complication after allogeneic stem cell transplantation. Poor prognosis has been shown in patients with cGVHD after the failure of primary steroid-based treatments. A previous report demonstrated the efficacy and safety of ibrutinib in these patients, leading to the approval of ibrutinib for cGVHD in Japan. Here, we report the extended follow-up of patients in this study. To evaluate the safety and efficacy of ibrutinib in Japanese patients with steroid-dependent or refractory cGVHD. An open-label, single-arm, multicenter study of ibrutinib in Japanese patients with steroid-dependent or refractory cGVHD (NCT No.: NCT03474679; Clinical Registry No.: CR108443). At the time of the final data cutoff, 7/19 (36.8%) patients completed the study treatment, and 12/19 (63.2%) patients discontinued ibrutinib. After a median follow-up of 31.11 months (range:1.9 to 38.6 months), the best overall response rate was 84.2% (16/19 patients; 95% CI:60.4%, 96.6%) in all treated populations, with a median time to response of 2.81 (range:1.0 to 27.6) months. Of 15 responders with ≥2 organs involved at baseline, seven (46.7%) had responses in multiple organs. An improvement in the organ response rate was observed for the skin, eye, mouth, and esophagus compared with that in a previous report. The rate of sustained response for ≥20 weeks, ≥32 weeks, and ≥44 weeks were 68.8%, 62.5%, and 50.0%, respectively for 16 responders. The median daily corticosteroid dose requirement tended to decrease over time for all treated analysis sets. Twelve of 19 patients (63.2%) reached a corticosteroid dose of <0.15 mg/kg/day for at least one week, and four (21.1%) discontinued corticosteroid treatment for at least 28 days during the study. The failure-free and overall survival rates at 30 months were 62.7% and 62.0%, respectively. The safety findings of this updated analysis were consistent with the safety profile observed at the time of the primary analysis and the known ibrutinib safety profile. Common grade ≥3 treatment-emergent adverse events (TEAEs) were pneumonia (6/19 [31.6%] patients), platelet count decreased, and cellulitis (3/19 [15.8%] patients each). After the primary analysis, no new TEAEs leading to death, treatment discontinuation, or dose reduction were reported, and no new patients reported major hemorrhage. Cardiac arrhythmia (Grade 2 atrial flutter) was reported in 1/19 (5.3%) patients. No new safety signs were observed despite prolonged ibrutinib exposure. The final results support previous conclusions, demonstrating a clinically meaningful response and acceptable safety profile of ibrutinib in Japanese patients with steroid-dependent or refractory cGVHD.

Effectiveness and Safety of Ibrutinib in Patients with Mantle Cell Lymphoma (MCL) in Belgian Routine Clinical Practice: 3-Year Follow-up

Background: Belgian ibrutinib Real-world Data (BiRD) is a multicenter, non-interventional, observational, cohort study of adults with a confirmed diagnosis of chronic lymphocytic leukemia, MCL, or Waldenström's macroglobulinemia. Aim: To assess the effectiveness and safety of ibrutinib treatment in relapsed/refractory MCL in routine clinical practice. Methods: Eligible patients initiated reimbursed ibrutinib treatment upon or after commercial availability in Belgium (August 1, 2015); or participated in the Medical Need Program and switched to reimbursed ibrutinib with commercial availability. The primary outcome measures were progression-free survival (PFS) and overall response rate (ORR); secondary outcome measures included overall survival (OS), time to next treatment (TTNT), and safety. Data were collected both prospectively (pro) and retrospectively (ret). Ret collected adverse events (AEs) included only those considered related to ibrutinib, whereas pro collected AEs included all treatment-emergent AEs (TEAEs); therefore, TEAEs/AEs are reported separately for the pro/ret groups. Total population effectiveness results were adjusted with left truncation. We report results from the third interim analysis (March 31, 2020 cutoff) for patients with relapsed/refractory MCL, with a median follow-up of 35.8 months. Results: The effectiveness and safety populations included 76 patients (pro, n = 20; ret, n = 56). Median age at ibrutinib initiation was 74 years (range, 47-88); 76.3% were male; median time from diagnosis to ibrutinib initiation was 2.8 years (range, 0.1-17.3). Most patients received 1 (51.3%) or 2 (31.6%) prior lines of therapy, which was most frequently combination therapy (72.4%). Common therapies received in the most recent prior line of treatment were R-CHOP/R-miniCHOP (23.7%), R-DHAP/R-DHAX/R-DHAC (14.5%), alternating R-CHOP/R-DHAP (11.8%), bendamustine (10.5%), and R-bendamustine (10.5%). Complete response (CR; 58.2%) or partial response (PR; 17.9%) was the most common best response to most recent prior therapy. The majority of patients progressed (87.7%) following the most recent prior therapy, and median time from progression to initiation of ibrutinib was 0.72 months (range, 0-25.1). Lymphadenopathy and/or splenomegaly (56.6%) was the most common reason for initiating ibrutinib treatment. Ibrutinib was initiated at 560 mg/day in 85.5% of patients, and 37 patients (48.7%) had ≥ 1 dose modification. With ibrutinib treatment, median PFS was 18.6 months in the overall MCL population (Figure), and 21.5/26.8 months in the pro/ret groups. ORR was 93.4% (CR 39.5%, PR 53.9%). Median TTNT was 18.9 months (34.9/29.1 months in pro/ret) and median OS was 32.2 months (not estimable/43.2 months in pro/ret). Main effectiveness outcomes stratified according to age, prior line of therapy, and progression ≤ 24 and > 24 months from last prior therapy (for patients with 1 prior line of therapy) are listed in the Table. TEAEs/AEs and serious TEAEs/AEs were reported in 100.0/80.4% and 85.0/50.0% in the pro/ret groups, respectively. TEAEs/AEs led to dose reduction, interruption, or withdrawal in 30.0/8.9%, 45.0/30.4%, and 30.0/17.9% of patients in the pro/ret groups, respectively. TEAEs/AEs of interest in the pro/ret groups were major bleeding (10.0/3.6%), infection (55.0/58.9%), hypertension (10.0/3.6%), atrial fibrillation (15.0/12.5%), arthralgia/myalgia (10.0/7.1%), diarrhea (35.0/17.9%), and rash (10.0/8.9%). Ibrutinib was permanently discontinued in 58 patients (76.3%), most commonly due to disease progression (n = 29, 54.7% [5 patients missing reasons for discontinuation]). Conclusions: Ibrutinib is an effective treatment for patients with relapsed/refractory MCL in a representative real-world population across various patient subgroups; results are consistent with those from clinical trials (Dreyling et al. Hemasphere. 2022;6(5):e712). TEAEs/AEs were consistent with the known safety profile of ibrutinib. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Effectiveness and Safety of Ibrutinib for Chronic Lymphocytic Leukemia in Routine Clinical Practice: 3-Year Follow-up of the Belgian Ibrutinib Real-World Data (BiRD) Study

The multicenter observational BiRD study investigated the real-world effectiveness and safety of ibrutinib in patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL) and Waldenström’s macroglobulinemia (WM) in Belgium. This interim analysis reports results for patients with CLL, with a median follow-up of 34 months. Overall, patients had predominantly relapsed/refractory disease (73%) and were elderly (median age 72 years) with high-risk features such as del17p and/or TP53 mutations (59%). Patients were included either prospectively or retrospectively, and the total patient population effectiveness results were adjusted with left truncation. In the effectiveness population (N = 221: prospective, n = 71; retrospective, n = 150), the overall response rate was 90.0%. Median progression-free survival was 38.3 months (prospective, not estimable; retrospective, 51.5 months) and median overall survival was not yet estimable in the total, prospective and retrospective groups. Treatment-emergent adverse events (TEAEs) for the prospective and retrospective groups are reported separately. Any-grade TEAEs of interest in the prospective/retrospective groups included infections (67.1%/60.1%), diarrhea (20.5%/10.5%), hypertension (16.4%/9.8%) and atrial fibrillation (12.3%/7.2%). Major bleeding was reported in 5.5%/3.3% of prospective/retrospective patients, with little difference observed between those receiving versus not receiving antithrombotic treatment. Discontinuations due to toxicity were reported in 10.5% of patients. Results from this interim analysis show treatment with ibrutinib to be effective and tolerable, with no new safety signals observed. Future analyses will report on longer-term follow-up.

Safety and Efficacy of Ibrutinib in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Who Have Undergone Prior Allogeneic Stem Cell Transplant

Introduction: Ibrutinib (Imbruvica®), a first-in-class Bruton’s tyrosine kinase inhibitor is a once-daily single-agent approved by the US FDA for patients with chronic lymphocytic leukemia (CLL) who have received ≥1 prior therapy, and for CLL with a 17p deletion. The phase III trial evaluating the efficacy and safety of ibrutinib in patients with relapsed/refractory CLL or small lymphocytic leukemia has previously been reported (Byrd et al. N Engl J Med, 2014). Allogeneic hematopoietic stem cell transplantation (HSCT) is also used to treat CLL, particularly in those who are at high risk. Patients with CLL who relapse after allogeneic HSCT are extremely difficult to treat with chemotherapy due to impaired hematopoietic reserve and/or infections. Furthermore, both B and T cells are known to play a role in the immunopathophysiology of graft-versus-host disease (GVHD), and in preclinical studies, ibrutinib, which inhibits both ITK and BTK, reversed established chronic GVHD. To evaluate whether ibrutinib is safe and effective in treating patients with CLL with a history of prior allogeneic HSCT, we evaluated the subset of patients enrolled in ibrutinib clinical trials who had undergone prior HSCT.Methods: Data were collected for patients with relapsed/refractory CLL who had undergone allogeneic HSCT and had been treated with ibrutinib, either as a single agent or in combination with ofatumumab, in 1 of 4 clinical trials (PCYC-1102, PCYC-1109, PCYC-1112, and PCYC-1117). Two of the studies (PCYC-1112 and PCYC-1117) allowed only patients who were >6 months post-HSCT and without GVHD to enroll. Efficacy evaluations included assessment of overall response rate (ORR) by iwCLL criteria, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Safety evaluations included reporting of adverse events (AEs), including serious AEs (SAEs).Results: A total of 16 patients from 4 ibrutinib clinical trials had undergone prior allogeneic HSCT. Median patient age was 54.5 years (range, 43-68); 12.5% were ≥ 65 years of age, 11 were male, and all 16 patients had an ECOG performance status of 0 or 1. Chromosomal abnormalities del17p and del11q were reported in 10 and 3 patients, respectively. More than 4 prior therapies were reported for 12 patients. Of the 16 patients, 13 had received an intervening salvage therapy between allogeneic HSCT and the start of ibrutinib treatment. The median time since the most recent transplant was 27 months (range, 8-115). Baseline neutropenia, anemia, and thrombocytopenia were reported in 31%, 25%, and 38%, respectively. Median time on ibrutinib was 18.1 months (range, 0.4-38.8) including 12 patients who were treated with ibrutinib for >12 months. At the time of data cut-off, 11 patients were continuing treatment. Reasons for discontinuation included disease progression (n=2), AEs (n=2), and withdrawal of consent (n=1). No dose reductions were reported. Investigator-assessed responses included 2 complete responses, 9 partial responses, and 3 partial responses with lymphocytosis, resulting in a best ORR of 87.5%. Median DOR, median PFS, and median OS were not reached at a median follow-up of 23 months. The 24-month PFS and OS rates were each 77% and 75%, respectively. Treatment-emergent grade ≥3 SAEs were observed in 11 patients and included infections (n=6), with the remaining events occurring in 1 patient each, including febrile neutropenia, atrial flutter, colitis, perirenal hematoma, subdural hematoma, postprocedural hemorrhage, hypercalcemia, bone lesion, syncope, hematuria, urinary retention, and dyspnea. The only AE leading to discontinuation of ibrutinib was pneumonia in 2 patients; both were fatal events (at 0.9 and 2.3 months). Two additional deaths occurred on study due to disease progression at 24 and 28 months.Conclusion: Ibrutinib was well tolerated in patients who had undergone prior allogeneic HSCT, with a safety profile similar to that observed in the overall population of patients with relapsed/refractory CLL. The best ORR of 87.5% in this subgroup was also consistent with the 90% reported for the broader relapsed/refractory population in the PCYC-1102 study of single-agent ibrutinib. These data support use of ibrutinib in CLL patients with previous allogeneic HSCT and exploration of ibrutinib treatment for chronic GVHD (ongoing clinical trial: clinicaltrials.gov NCT 02195869). DisclosuresCoutre:Janssen, Pharmacyclics: Honoraria, Research Funding. O’Brien:Amgen, Celgene, GSK: Consultancy; CLL Global Research Foundation: Membership on an entity’s Board of Directors or advisory committees; Emergent, Genentech, Gilead, Infinity, Pharmacyclics, Spectrum: Consultancy, Research Funding; MorphoSys, Acerta, TG Therapeutics: Research Funding. Byrd:Pharmacyclics: Research Funding. Hillmen:Pharmacyclics, Janssen, Gilead, Roche: Honoraria, Research Funding. Brown:Sanofi, Onyx, Vertex, Novartis, Boehringer, GSK, Roche/Genentech, Emergent, Morphosys, Celgene, Janssen, Pharmacyclics, Gilead: Consultancy. Mato:Pharamcyclics, Genentech, Celegene, Millennium : Speakers Bureau. Miklos:Pharmacyclics: Research Funding. Zhou:Pharmacyclics: Employment. Fardis:Pharmacyclics: Employment. Styles:Pharmacyclics: Employment. Jaglowski:Pharmacyclics: Research Funding.

Efficacy and Safety of Ibrutinib in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia with 17p Deletion: Results from the Phase II RESONATE™-17 Trial

▪Background: Patients with chronic lymphocytic leukemia (CLL) with deletion of the short arm of chromosome 17 (del 17p) follow an aggressive clinical course and demonstrate a median survival of less than 2 years in the relapsed/refractory (R/R) setting. Ibrutinib (ImbruvicaTM), a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, has been approved for previously treated patients with CLL and for patients with del 17p CLL. We report results from the primary analysis of the Phase II RESONATETM-17 (PCYC-1117-CA) study, designed to evaluate the efficacy and safety of single-agent ibrutinib for treatment of patients with R/R del 17p CLL or small lymphocytic leukemia (SLL).Methods: Patients with del 17p CLL or SLL who failed at least one therapy were enrolled to receive 420 mg oral ibrutinib once daily until progression. All patients receiving at least one dose of ibrutinib were included in the analysis. The primary endpoint was overall response rate (ORR) per an independent review committee (IRC). Other endpoints included duration of response (DOR), progression-free survival (PFS), and safety of ibrutinib.Results: Among 144 treated patients (137 with CLL, 7 with SLL), the median age was 64 (48% 65 years or older) and all had del 17p. Baseline characteristics included 63% of patients with Rai Stage III or IV disease, 49% with bulky lymphadenopathy of at least 5 cm, and 10% with lymphadenopathy of least 10 cm. The median baseline absolute lymphocyte count (ALC) was 32.9 x 109/L with 57% of patients with a baseline ALC at least 25.0 x 109/L. Baseline beta-2 microglobulin levels were at least 3.5 mg/L in 78% of patients (range 1.8-19.8 mg/L), and lactate dehydrogenase levels were at least 350 U/L in 24% of patients (range 127-1979 U/L). A median of 2 prior therapies (range 1-7) was reported. Investigator-assessed ORR was 82.6% including 17.4% partial response with lymphocytosis (PR-L). Complete response (CR)/complete response with incomplete bone marrow recovery (CRi) were reported in 3 patients. IRC-assessed ORR is pending. At a median follow up of 13.0 months (range 0.5-16.7 months), the median PFS (Figure 1) and DOR by investigator determination had not been reached. At 12 months, 79.3% were alive and progression-free, and 88.3% of responders were progression-free. Progressive disease was reported in 20 patients (13.9%). Richter transformation was reported in 11 of these patients (7.6%), 7 of the cases occurring within the first 24 weeks of treatment. Prolymphocytic leukemia was reported in 1 patient. The most frequently reported adverse events (AE) of any grade were diarrhea (36%; 2% Grade 3-4), fatigue (30%; 1% Grade 3-4), cough (24%; 1% Grade 3-4), and arthralgia (22%; 1% Grade 3-4). Atrial fibrillation of any grade was reported in 11 patients (7.6%; 3.5% Grade 3-4). Seven patients reported basal or squamous cell skin cancer and 1 patient had plasma cell myeloma. Most frequently reported Grade 3-4 AEs were neutropenia (14%), anemia (8%), pneumonia (8%), and hypertension (8%). Major hemorrhage was reported in 7 patients (4.9%, all Grade 2 or 3). Study treatment was discontinued in 16 patients (11.1%) due to AEs with 8 eventually having fatal events (pneumonia, sepsis, myocardial or renal infarction, health deterioration). At the time of data cut, the median treatment duration was 11.1 months, and 101 of 144 patients (70%) continued treatment with ibrutinib.Conclusions: In the largest prospective trial dedicated to the study of del 17p CLL/SLL, ibrutinib demonstrated marked efficacy in terms of ORR, DOR, and PFS, with a favorable risk-benefit profile. At a median follow up of 13 months, the median DOR had not yet been reached; 79.3% of patients remained progression-free at 12 months, consistent with efficacy observed in earlier studies (Byrd, NEJM 2013;369:32-42). The PFS in this previously treated population compares favorably to that of treatment-naïve del 17p CLL patients receiving fludarabine, cyclophosphamide, and rituximab (FCR) (Hallek, Lancet 2010;376:1164-74) or alemtuzumab (Hillmen, J Clin Oncol 2007;10:5616-23) with median PFS of 11 months. The AEs are consistent with those previously reported for ibrutinib (Byrd, NEJM 2014;371:213-23). These results support ibrutinib as an effective therapy for patients with del 17p CLL/SLL. [Display omitted] DisclosuresO’Brien:Amgen, Celgene, GSK: Consultancy; CLL Global Research Foundation: Membership on an entity’s Board of Directors or advisory committees; Emergent, Genentech, Gilead, Infinity, Pharmacyclics, Spectrum: Consultancy, Research Funding; MorphoSys, Acerta, TG Therapeutics: Research Funding. Jones:Pharmacyclics: Consultancy, Research Funding. Coutre:Janssen, Pharmacyclics: Honoraria, Research Funding. Mato:Pharamcyclics, Genentech, Celegene, Millennium : Speakers Bureau. Hillmen:Pharmacyclics, Janssen, Gilead, Roche: Honoraria, Research Funding. Tam:Pharmacyclics and Janssen: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Siddiqi:Janssen: Speakers Bureau. Furman:Pharmacyclics: Consultancy, Speakers Bureau. Brown:Sanofi, Onyx, Vertex, Novartis, Boehringer, GSK, Roche/Genentech, Emergent, Morphosys, Celgene, Janssen, Pharmacyclics, Gilead: Consultancy. Stevens-Brogan:Pharmacyclics: Employment. Li:Pharmacyclics: Employment. Fardis:Pharmacyclics: Employment. Clow:Pharmacyclics: Employment. James:Pharmacyclics: Employment. Chu:Pharmacyclics: Employment, Equity Ownership. Hallek:Janssen, Pharmacyclics: Consultancy, Research Funding. Stilgenbauer:Pharmacyclics, Janssen Cilag: Consultancy, Honoraria, Research Funding.