CLL-139: Acalabrutinib ± Obinutuzumab vs Obinutuzumab + Chlorambucil in Treatment-Naïve Chronic Lymphocytic Leukemia: ELEVATE-TN 4-Year Follow-up

2021 ◽  
Vol 21 ◽  
pp. S318-S319
Author(s):  
Jeff P. Sharman ◽  
Miklos Egyed ◽  
Wojciech Jurczak ◽  
Alan Skarbnik ◽  
John M. Pagel ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Treatment Naïve ◽  
Tn 4

scholarly journals PF377 ACALABRUTINIB WITH OBINUTUZUMAB IN TREATMENT-NAIVE AND RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA: 3-YEAR FOLLOW-UP

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 140
Author(s):  
J.A. Woyach ◽  
K. Rogers ◽  
S. Bhat ◽  
J. Blachly ◽  
M. Jianfar ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Treatment Naïve

Acalabrutinib With Obinutuzumab in Treatment-Naive and Relapsed/Refractory Chronic Lymphocytic Leukemia: 3-Year Follow-Up

2019 ◽  
Vol 37 ◽  
pp. 209-210
Author(s):  
J. Woyach ◽  
K.A. Rogers ◽  
S. Bhat ◽  
J. Blachly ◽  
M. Jianfar ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Treatment Naïve

scholarly journals Efficacy and Safety of Ibrutinib in Elderly Patients with Chronic Lymphocytic Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5478-5478
Author(s):  
Zhijian Cao ◽  
Jun Ma
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Elderly Patients ◽  
Tp53 Mutation ◽  
Overall Response Rate ◽  
Single Agent ◽  
Lymphocytic Leukemia ◽  
Serious Adverse Events ◽  
Free Survival ◽  
Treatment Naïve

Background: For most of the elderly chronic lymphocytic leukemia (CLL) patients, treatment outcome focus on achievement of clinical response, relief of symptoms and prolongation of life expectancy, but comorbidities, frailty and reduced functional status in elderly patients make the standard treatments intolerable and less efficacious. Single agent Ibrutinib (Ibr), an inhibitor of oral Bruton's tyrosine kinase, is approved for the front-line treatment of patients with CLL by Chinese Food and Drug Administration (CFDA) in 2017. Objectives: This study evaluated effeicacy and safety of single agent Ibrutinib in elderly patients with treatment-naive chronic lymphocytic leukemia for 2 years in our center. Methods: Patients over 65 years old with previously untreated CLL/SLL (n = 37) were received Ibr 420 mg once daily continuously until disease progression or unacceptable toxicity. We examined baseline demographics/disease characteristics, endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety in patients with CLL receiving ibrutinib. Results: 37 CLL patients over 65 years old were enrolled and treated with from June 2017 to May 2019 in our center. The median follow-up was 19.4 months (range, 0.8-31.6 months). Their F/M ratio was 16/21 and the median age of the enrolled population was 77.3 years (range, 65.4-92.7 years). 31 (83.8%) patients had an Eastern Cooperative Oncology Group performance status of 0-1. In these patients, 18/34 (52.9%) had del17p and/or TP53 mutation, and 20/30 (66.7%) had unmutated IGHV. With Ibr, Overall response rate (ORR) was 91.9%; complete response (CR) was 8.0%, partial response (PR) was 51.4%, and PR with lymphocytosis (PRwL) was 32.4%. Median progress free survival (PFS) was 17.3 months (95% CI, 14.3-24.0); PFS rates at 12 and 24 months were 87.1% and 74.0%, respectively. Median PFS with ibrutinib was comparable in pts with/without del17p and/or TP53 mutation (16.4 [95% CI, 14.3-NE] vs 14.5 months [95% CI, 13.9-NE]) and with unmutated/mutated IGHV (16.8 [95% CI, 12.1-22.8] vs 19.7 months [95% CI, 14.3-23.0]). Overall survival (OS) rates were 95.8% and 86.8% at 12 and 24 months, respectively. Median time to best response was 4.8 months (95% confidence interval [CI], 3.7-5.5). With median follow-up of 19.4 months, 21.6% (8/37) of pts had progressed or died. In the safety analysis, the most common serious adverse events (AEs) were recorded in 6 patients include neutropenia (4 pts), pneumonia (3 pts), hypertension (3 pts), anemia (2 pts), hyponatremia (2 pts), and atrial fibrillation (2 pts). AEs of any grade leading to ibr discontinuation occurred in 3 pts over time. Conclusions: In total, single agent ibrutinib was well tolerated and yielded high response rates, including for pts with high-risk genomic features, that were durable and deepened over time in treatment-naive elderly patients with CLL. Ibrutinib also had sustained PFS and OS benefit. Safety profile was acceptable and the most serious adverse events were neutropenia, pneumonia, hypertension, anemia, hyponatremia, and atrial fibrillation. Disclosures No relevant conflicts of interest to declare.

Acalabrutinib in treatment-naïve chronic lymphocytic leukemia: Mature results from phase II study demonstrating durable remissions and long-term tolerability.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8024-8024 ◽  
Author(s):  
John C. Byrd ◽  
Jennifer Ann Woyach ◽  
Richard R. Furman ◽  
Peter Martin ◽  
Susan Mary O'Brien ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Upper Respiratory Tract ◽  
Bleeding Events ◽  
Phase 3 ◽  
Treatment Naïve ◽  
Melanoma Skin

8024 Background: The next-generation Bruton tyrosine kinase inhibitor acalabrutinib was approved in patients (pts) with treatment-naïve (TN) and relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) based on two complementary phase 3 studies, ELEVATE-TN and ASCEND. This report of ACE-CL-001 (NCT02029443), the first phase 2 study of acalabrutinib, provides the longest safety and efficacy follow-up to date in symptomatic TN CLL pts. Methods: Adults with TN CLL/SLL were eligible if they met iwCLL 2008 criteria for treatment, were inappropriate for/declined standard chemotherapy and had ECOG performance status 0–2. Pts received acalabrutinib 100 mg BID or 200 mg QD, later switching to 100 mg BID, until progressive disease (PD) or unacceptable toxicity. Primary endpoint was safety. Events of clinical interest (ECI) were based on combined AE terms for infections, bleeding events, hypertension, and second primary malignancies (SPM) excluding non-melanoma skin, and on a single AE term for atrial fibrillation. Additional endpoints included investigator-assessed overall response rate (ORR), duration of response (DOR), time to response (TTR), and event-free survival (EFS). Results: Ninety-nine pts (n = 62 100 mg BID; n = 37 200 mg QD), were treated [median age: 64 years, 47% Rai stage 3–4 disease, 10% del(17p), 62% unmutated IGHV]. At median follow-up of 53 months (range, 1–59), 85 (86%) pts remain on treatment; most discontinuations were due to AEs (n = 6) or PD (n = 3 [n = 1 Richter transformation]). Most common AEs (any grade) were diarrhea (52%), headache (45%), upper respiratory tract infection (44%), arthralgia (42%), and contusion (42%). All-grade and grade ≥3 ECIs included infection (84%, 15%), bleeding events (66%, 3%), and hypertension (22%, 11%). Atrial fibrillation (all grades) occurred in 5% of pts (incidence: 1% in years 1, 2, 4; 3% in year 3). SPMs excluding non-melanoma skin (all grades) occurred in 11%. Serious AEs were reported in 38% of pts; those in > 2 pts were pneumonia (n = 4) and sepsis (n = 3). ORR was 97% (7% complete response; 90% partial response). Median TTR was 3.7 months (range, 2–22). Response rates were similar across high-risk groups. Median DOR and median EFS were not reached; 48-month DOR rate was 97% (95% CI, 90%–99%), and 48-month EFS rate was 90% (95% CI, 82%–94%). Conclusions: Long-term data from ACE-CL-001 further support the favorable results with acalabrutinib in phase 3 studies and demonstrate durable responses with no new long-term safety issues. Clinical trial information: NCT02029443 .

scholarly journals Long-Term Follow up of Front-Line Therapy with Ofatumumab, High Dose Methylprednisolone and Lenalidomide (HiLO trial) for Treatment-Naïve Chronic Lymphocytic Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3150-3150
Author(s):  
Ariel Felipe Grajales-Cruz ◽  
Julio C. Chavez ◽  
Elyce P. Turba ◽  
Lisa Nodzon ◽  
Francisco Perez Leal ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Research Funding ◽  
Treatment Phase ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Front Line ◽  
High Dose Methylprednisolone ◽  
Treatment Naïve ◽  
Grade 3

Abstract Background: New targeted therapies continue to show improved efficacy in various stages of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), sparing patients from chemoimmunotherapy. However, cure remains elusive. Here, we present a front-line alternative based on a combination of high-dose methylprednisolone (HDMP) and ofatumumab, followed by consolidative therapy with lenalidomide plus ofatumumab. Methods: This is a phase II, single-center study in patients with treatment-naive (TN) CLL/SLL. During the first treatment phase (cycles 1-3) patients received HDMP 1000 mg/m2 IV and ofatumumab 2000 mg (300 mg given week 1 then 2000 mg for a total of 12 doses) IV infusions weekly x 4 doses in cycle 1 of a 28 day cycle, then every 2 weeks for cycles 2 and 3. During the second treatment phase (cycles 4-12), patients received renally adjusted lenalidomide 5-10 mg daily and ofatumumab 2000mg IV once every 8 weeks. Growth factor support was permitted at the discretion of treating physician. Prophylactic medications included allopurinol for tumor lysis syndrome (TLS) 3 days before C1D1 through C1; and trimethoprim/sulfamethoxazole and fluconazole through cycle 4, and acyclovir through C12. Patients received aspirin 81 mg/day as thrombosis prophylaxis while on lenalidomide. Patients were assessed for response by iwCLL 2008 criteria (including imaging assessment) after completion of cycles 3 and 12. The study allowed continuation of lenalidomide if patients achieved complete (CR), partial (PR) response or stable disease (SD). Primary endpoints were efficacy, adverse events (AEs) profile, and time-to-treatment failure (TTF). Results: Between January 2012 and September 2015, the study enrolled a total of 45 patients. Median follow-up was 50.4 (5.6-72.8) months. The median age was 62.6 (48.2-86.1) years. Chromosomal analysis by FISH demonstrated Del17p in 8 (17.8%), Del11q (+/- others, except Del17p) in 10 (22.2%), Trisomy 12 (+/- others, except Del17p and Del11q) in 8 (17.8%), Del13q in 10 (22.2%), no mutations in 9 (20%) patients. The IGHV status was unmutated in 34 (75.6%) cases. Indications to start treatment were: symptomatic lymphadenopathy, symptomatic splenomegaly, anemia, and thrombocytopenia in 5 (11.1%), 10 (22.2%), 12 (26.7%), and 18 (40%), respectively. The median duration of treatment was 35.6 (2.7-66.9) months. Reasons for treatment discontinuation were: progressive disease (PD) in 9 (20%), AEs in 15 (33.3%), transplantation in 3 (6.7%), consent withdrawal in 1 (2.2%), and secondary malignancies in 2 (4.4%) cases. The overall response rates (PR+CR) at 3, 12, 24, 36, and 48 months were 75.6%, 77.8%, 66.7%, 44.4%, and 37.8%, respectively. The CR rates at 3, 12, 24, 36, and 48 months were 2.2%, 11.1%, 20%, 17.8%, and 13.3% respectively. Fifteen patients remain in PR/CR and on treatment at the time of this analysis. The intention-to-treat median TTF was 45.2 (2.9-69.7) months, and was not different among high risk groups such as Del17p, Del11q and/or unmutated IgHV. In patients who discontinued for reasons other than PD the median duration of response without treatment was 30.7 (9.8-69.7) months. Three (6.7%) patients underwent allogeneic hematopoietic cell transplantation after a median of 3 (3 - 4) treatment cycles. Treatment was well tolerated with grade 3/4 infusion reaction in 1 (2.2%) patient. Grade 3/4 treatment-related hematological AEs were neutropenia, thrombocytopenia, and anemia in 33 (73.3%), 5 (11.1%), and 1 (2.2%), respectively. Grade 3/4 infections occurred in 6 (13.3%) patients. No grade 3/4 tumor flares were observed, and there were no cases of TLS or thrombosis. Conclusion: The combination of ofatumumab, HDMP and lenalidomide is effective and well tolerated in treatment-naive CLL/SLL, even when poor prognostic features are present. Disclosures Komrokji: Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau. Locke:Novartis Pharmaceuticals: Other: Scientific Advisor; Cellular BioMedicine Group Inc.: Consultancy; Kite Pharma: Other: Scientific Advisor. Kharfan-Dabaja:Seattle Genetics: Speakers Bureau; Incyte Corp: Speakers Bureau; Alexion Pharmaceuticals: Speakers Bureau. Sokol:Spectrum Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy; Mallinckrodt Pharmaceuticals: Consultancy.

Acalabrutinib ± obinutuzumab versus obinutuzumab + chlorambucil in treatment-naïve chronic lymphocytic leukemia: Elevate-TN four-year follow up.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7509-7509
Author(s):  
Jeff Porter Sharman ◽  
Miklos Egyed ◽  
Wojciech Jurczak ◽  
Alan Skarbnik ◽  
John M. Pagel ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Progressive Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Early Results ◽  
Treatment Naïve ◽  
Group A

7509 Background: Early results from ELEVATE-TN (NCT02475681) at a median follow-up of 28.3 mo demonstrated superior efficacy of acalabrutinib (A) ± obinutuzumab (O) compared with O + chlorambucil (Clb) in patients (pts) with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) (Sharman et al. Lancet 2020;395:1278-91). Results from a 4-year update are reported here. Methods: Pts received A±O or O+Clb. Crossover to A monotherapy was permitted in pts who progressed on O+Clb. Investigator-assessed (INV) progression-free survival (PFS), INV overall response rate (ORR), overall survival (OS), and safety were evaluated. Results: 535 pts (A+O, n=179; A, n=179; O+Clb, n=177) were randomized with a median age of 70 y; 63% had unmutated IGHV and 9% del(17p). At a median follow-up of 46.9 mo (range, 0.0–59.4; data cutoff: Sept 11, 2020), the median PFS was not reached (NR) for A+O and A pts vs 27.8 mo for O+Clb pts (both P<0.0001). In pts with unmutated IGHV, the median PFS was NR (A+O and A) vs 22.2 mo among O+Clb pts (both P<0.0001). In pts with del(17p), the median PFS was NR (A+O and A) vs 17.7 mo for O+Clb ( P<0.005). Estimated 48-mo PFS rates were 87% for A+O, 78% for A, and 25% for O+Clb. Median OS was NR in any treatment arm with a trend towards significance in the A+O group (A+O vs O+Clb, P=0.0604); estimated 48-mo OS rates were 93% (A+O), 88% (A), and 88% (O+Clb). ORR was significantly higher with A+O (96.1%; 95% CI 92.1–98.1) vs O+Clb (82.5%; 95% CI 76.2–87.4; P<0.0001); ORR with A was 89.9% (95% CI 84.7–93.5; P=0.035 vs O+Clb). Complete response/complete response with incomplete hematologic recovery (CR/CRi) rates were higher with A+O (26.8%/3.9%) vs O+Clb (12.4%/0.6%); 10.6%/0.6% had CR/CRi with A. Common adverse events (AEs) and AEs of interest are shown in the Table. Overall treatment discontinuation rates were 25.1% (A+O), 30.7% (A), and 22.6% (O+Clb); the most common reasons were AEs (12.8%, 12.3%, 14.7%, respectively) and progressive disease (4.5%, 7.8%, 1.7%). Most pts (77.4%) completed O+Clb treatment. Conclusions: With a median follow-up of 46.9 mo (̃4y), the efficacy and safety of A+O and A monotherapy was maintained, with an increase in CR since the interim analysis (from 21% to 27% [A+O] and from 7% to 11% [A]) and low rates of discontinuation.[Table: see text]

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