scholarly journals Updates from the American Society of Hematology 2019 annual meeting: practice-changing studies in treatment-naïve chronic lymphocytic leukemia

2020 ◽  
Vol 27 (2) ◽  
Author(s):  
Versha Banerji ◽  
Peter Anglin ◽  
Anna Christofides ◽  
Sarah Doucette ◽  
Pierre Laneuville
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Annual Meeting ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Meeting Report ◽  
Efficacy And Safety ◽  
Treatment Naïve ◽  
American Society

The 2019 annual meeting of the American Society of Hematology took place 7–10 December in Orlando, Florida. At the meeting, results from key studies in treatment-naïve chronic lymphocytic leukemia were presented. Of those studies, phase III oral presentations focused on the efficacy and safety of therapy with Bruton tyrosine kinase (BTK) and B-cell lymphoma-2 (BCL-2) inhibitors. One presentation reported updated results of the ECOG 1912 trial comparing the efficacy and safety of ibrutinib plus rituximab to fludarabine, cyclophosphamide, rituximab in patients with CLL younger than 70 years of age. A second presentation reported interim results of the ELEVATE-TN trial, which is investigating the efficacy and safety of acalabrutinib plus obinutuzumab or acalabrutinib monotherapy versus chlorambucil plus obinutuzumab. A third presentation reported on the single-agent zanubrutinib arm of the SEQUOIA trial in patients with del(17p). The final presentation reported a data update from the CLL14 trial, which is evaluating fixed-duration venetoclax and obinutuzumab versus chlorambucil and obinutuzumab, including the association of minimal residual disease status on progression-free survival. Our meeting report describes the foregoing studies and presents interviews with investigators and commentaries by Canadian hematologists about potential effects on Canadian practice.

scholarly journals Highlights from ASCO 2020: updates on the treatment of chronic lymphocytic leukemia

2020 ◽  
Vol 27 (4) ◽  
Author(s):  
S. Dolan ◽  
A. Christofides ◽  
S. Doucette ◽  
M. Shafey
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Clinical Oncology ◽  
Scientific Meeting ◽  
Lymphocytic Leukemia ◽  
Annual Scientific ◽  
Meeting Report ◽  
Efficacy And Safety ◽  
Annual Scientific Meeting ◽  
Treatment Naïve ◽  
American Society

Because of the global coronavirus pandemic, the 2020 annual scientific meeting of the American Society of Clinical Oncology took place virtually 29–30 May. At the meeting, results from key studies about the treatment of chronic lymphocytic leukemia (cll) were disseminated. Studies examined the efficacy and safety of ibrutinib, acalabrutinib, zanubrutinib, and venetoclax as monotherapy or in combination with novel agents for patients with treatment-naïve and relapsed or refractory cll. Our meeting report describes the foregoing studies and presents interviews with investigators and commentaries by Canadian hematologists about potential effects on Canadian practice.

scholarly journals Updates from the 2017 American Society of Hematology annual meeting: practice-changing studies in untreated chronic lymphocytic leukemia

2018 ◽  
Vol 25 (1) ◽  
pp. 91
Author(s):  
C. Owen ◽  
C. Toze ◽  
A. Christofides
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Annual Meeting ◽  
Residual Disease ◽  
Treatment Strategies ◽  
Variable Region ◽  
Lymphocytic Leukemia ◽  
Meeting Report ◽  
Phase Ii Studies ◽  
Novel Treatment Strategies ◽  
American Society

The 2017 annual meeting of the American Society of Hematology took place 9–12 December in Atlanta, Georgia. At the meeting, the oral presentations included results from key studies on the first-line treatment of chronic lymphocytic leukemia. A series of phase ii studies focusing on the efficacy and safety of novel treatment strategies were especially notable. One concerned the health-related quality of life results from the gibb study, which had examined the combination of obinutuzumab and bendamustine. A second evaluated the venetoclax–ibrutinib regimen in patients with high-risk disease. The third assessed the combination of ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab in patients with mutated immunoglobulin heavy-chain variable region genes. The fourth examined the combination of ibrutinib, fludarabine, cyclophosphamide, and rituximab in younger patients. And the final study evaluated obinutuzumab–ibrutinib followed by a minimal residual disease strategy in fit patients. Our meeting report describes the foregoing studies and presents interviews with investigators and commentaries by Canadian hematologists about the potential effects on Canadian practice.

scholarly journals Safety Analysis of Two Randomized Controlled Studies of Venetoclax in Patients with Chronic Lymphocytic Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5472-5472
Author(s):  
Samer Al Hadidi ◽  
Rammurti Kamble ◽  
Courtney Nicole Miller-Chism ◽  
Martha P. Mims
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell Lymphoma ◽  
Safety Analysis ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Randomized Controlled ◽  
Randomized Controlled Studies ◽  
Common Grade ◽  
Treatment Naïve ◽  
Grade 3

ABSTRACT BACKGROUND Venetoclax blocks the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein, leading to cell death of Chronic Lymphocytic Leukemia (CLL) cells. Multiple studies have demonstrated the efficacy and safety of venetoclax for treatment of relapsed/refractory or treatment naïve CLL. METHODS We conducted an integrated safety analysis to characterize the frequency, severity, natural history, and outcomes of adverse events (AEs) with venetoclax versus comparators. Data were pooled from 2 completed phase III randomized controlled studies that had included 406 venetoclax -treated and 402 comparator-treated patients with CLL as a first line in treatment naïve patients and for relapsed/refractory disease (Table.1). Safety analyses included reporting of AEs using crude and exposure-adjusted incidence rates. RESULTS The median follow up duration is 25.95months (range: 23.8-28.1 months) for both venetoclax-treated and comparator-treated patients. Discontinuation because of AEs occurred at the same rate in both groups. When adjusted to exposure, hyperglycemia and diarrhea were the only common grade 3 AEs more often reported with venetoclax than with the comparators. The prevalence of common grade 3/4 AEs with venetoclax were <10% apart from neutropenia (55.2%) and infections/infestations (17.5%) though with adjustment to exposure time both of these side effects were more common in comparator arms (Table.2). Grade 3/4 venetoclax associated tumor lysis syndrome happened in 1.7%. CONCLUSIONS These results from an integrated analysis support a favorable benefit/risk profile of venetoclax in patients with CLL. Disclosures No relevant conflicts of interest to declare.

scholarly journals Single-agent ibrutinib versus chemoimmunotherapy regimens for treatment-naïve patients with chronic lymphocytic leukemia: A cross-trial comparison of phase 3 studies

2018 ◽  
Vol 93 (11) ◽  
pp. 1402-1410 ◽  
Author(s):  
Tadeusz Robak ◽  
Jan A. Burger ◽  
Alessandra Tedeschi ◽  
Paul M. Barr ◽  
Carolyn Owen ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Single Agent ◽  
Lymphocytic Leukemia ◽  
Phase 3 ◽  
Treatment Naïve

scholarly journals Chronic lymphocytic leukemia paradigm continues to be refined: news from the American Society of Hematology 2018 annual meeting

2019 ◽  
Vol 8 (2) ◽  
pp. IJH14
Author(s):  
Stefano Molica
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Trials ◽  
Chronic Lymphocytic Leukemia ◽  
Standard Of Care ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Phase Iii Trials ◽  
Prospective Phase ◽  
American Society ◽  
Anti Cd20

There were a number of important updates and advances presented at the 2018 Annual American Society of Hematology meeting. With respect to the treatment of chronic lymphocytic leukemia, the American Society of Hematology 2018 was notable for an improved understanding of ibrutinib-based therapies. In fact, three prospective Phase III trials presented at the meeting indicate, in turn, that ibrutinib alone, ibrutinib plus rituximab, or ibrutinib plus obinutuzumab, should be the new standard of care for chronic lymphocytic leukemia. However, additional clinical trials comparing chemo-immunotherapy with ibrutinib alone or in association with an anti-CD20 monoclonal antibody remain a reasonable avenue to complete results of these large studies.

Long-Term Follow-Up of Patients With Chronic Lymphocytic Leukemia (CLL) Receiving Fludarabine Regimens as Initial Therapy

Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1165-1171 ◽  
Author(s):  
M.J. Keating ◽  
S. O’Brien ◽  
S. Lerner ◽  
C. Koller ◽  
M. Beran ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Median Survival ◽  
Response Rate ◽  
Single Agent ◽  
Complete Response ◽  
Initial Therapy ◽  
Lymphocytic Leukemia ◽  
Poor Correlation ◽  
American Society ◽  
Febrile Episodes

One hundred seventy-four patients with progressive or advanced chronic lymphocytic leukemia (CLL) have received initial therapy with fludarabine as a single agent or fludarabine combined with prednisone. The overall response rate was 78% and the median survival was 63 months. No difference in response rate or survival was noted in the 71 patients receiving fludarabine as a single agent compared with the 103 patients who received prednisone in addition. The median time to progression of responders was 31 months and the overall median survival was 74 months. Patients over the age of 70 years had shorter survivals. Patients with advanced stage disease (Rai III and IV) had a somewhat shorter survival than earlier stage patients. More than half the patients who relapsed after fludarabine therapy responded to salvage treatment, usually with fludarabine-based regimens. Second remissions were more common in patients who had achieved a complete remission on their initial treatment. The CD4 and CD8 T-lymphocyte subpopulations decreased to levels in the range of 150 to 200/μL after the first 3 courses of treatment. Although recovery towards normal levels was slow, the incidence of infections was low in patients in remission (1 episode of infection for every 3.33 patient years at risk) and decreased with time off treatment. There was no association of infections or febrile episodes with the use of corticosteroids or the CD4 count at the end of treatment and a poor correlation with the increase in CD4 counts during remission. Infectious episodes were less common in patients who had a complete response compared with partial responders. Richter’s transformation occurred in 9 patients and Hodgkin’s disease occurred in 4 patients. Five other patients died from other second malignancies. Fludarabine appears to be an effective initial induction therapy with a reasonable safety profile for patients with CLL. © 1998 by The American Society of Hematology.

Venetoclax: A First-in-Class Oral BCL-2 Inhibitor for the Management of Lymphoid Malignancies

2017 ◽  
Vol 51 (5) ◽  
pp. 410-416 ◽  
Author(s):  
Amber C. King ◽  
Tim J. Peterson ◽  
Troy Z. Horvat ◽  
Mabel Rodriguez ◽  
Laura A. Tang
Keyword(s):  
Adverse Effect ◽  
B Cell ◽  
Data Extraction ◽  
Tumor Lysis Syndrome ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Efficacy And Safety ◽  
Lymphoid Malignancies ◽  
Oral Agents ◽  
American Society

Objective: To review the pharmacology, efficacy, and safety of venetoclax for treatment of lymphoid malignancies. Data Sources: A literature search was performed of PubMed and MEDLINE databases (2005 to September 2016), abstracts from the American Society of Hematology and the American Society of Clinical Oncology, and ongoing studies from clinicaltrials.gov. Searches were performed utilizing the following key terms: venetoclax, ABT-199, GDC-199, obatoclax, GX15-070, BCL-2 inhibitor, navitoclax, ABT-263, and Venclexta. Study Selection/Data Extraction: Studies of pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of venetoclax in lymphoid malignancies were identified. Data Synthesis: Recently, treatment of B-cell lymphoproliferative disorders has shifted from conventional cytotoxic chemotherapy to novel small-molecule inhibitors. The advent of recently Food and Drug Administration–approved oral agents ibrutinib and idelalisib has shifted the paradigm of chronic lymphocytic leukemia (CLL) treatment; however, complete remission is uncommon, and the outcome for patients progressing on these treatments remains poor. Attention has been focused on a novel target, the B-cell lymphoma-2 protein (BCL-2), which serves an essential role in regulation of apoptosis. Venetoclax has demonstrated efficacy in multiple subtypes of lymphoid malignancies, including patients with relapsed/refractory CLL harboring deletion 17p, with an overall response rate of nearly 80%. Venetoclax is generally well tolerated, with the significant adverse effect being tumor lysis syndrome, for which there are formal management recommendations. Conclusion: Venetoclax has demonstrated promising results in relapsed/refractory lymphoid malignancies, with an acceptable adverse effect profile. As the role of BCL-2 inhibition in various malignancies becomes further elucidated, venetoclax may offer benefit to a myriad other patient populations.

scholarly journals Single-agent ibrutinib in RESONATE-2™ and RESONATE™ versus treatments in the real-world PHEDRA databases for patients with chronic lymphocytic leukemia

2019 ◽  
Vol 98 (12) ◽  
pp. 2749-2760 ◽  
Author(s):  
Gilles Salles ◽  
Emmanuel Bachy ◽  
Lukas Smolej ◽  
Martin Simkovic ◽  
Lucile Baseggio ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Real World ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Relative Effectiveness ◽  
Single Agent ◽  
Cox Proportional Hazards ◽  
Lymphocytic Leukemia ◽  
Cox Proportional Hazards Model ◽  
Treatment Naïve

AbstractAfter analyzing treatment patterns in chronic lymphocytic leukemia (CLL) (objective 1), we investigated the relative effectiveness of ibrutinib versus other commonly used treatments (objective 2) in patients with treatment-naïve and relapsed/refractory CLL, comparing patient-level data from two randomized registration trials with two real-world databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated using a multivariate Cox proportional hazards model, adjusted for differences in baseline characteristics. Rituximab-containing regimens were often prescribed in clinical practice. The most frequently prescribed regimens were fludarabine + cyclophosphamide + rituximab (FCR, 29.3%), bendamustine + rituximab (BR, 17.7%), and other rituximab-containing regimens (22.0%) in the treatment-naïve setting (n = 604), other non-FCR/BR rituximab-containing regimens (38.7%) and non-rituximab–containing regimens (28.5%) in the relapsed/refractory setting (n = 945). Adjusted HRs (95% CI) for progression-free survival (PFS) and overall survival (OS), respectively, with ibrutinib versus real-world regimens were 0.23 (0.14–0.37; p < 0.0001) and 0.40 (0.22–0.76; p = 0.0048) in the treatment-naïve setting, and 0.21 (0.16–0.27; p < 0.0001) and 0.29 (0.21–0.41; p < 0.0001) in the relapsed/refractory setting. When comparing real-world use of ibrutinib (n = 53) versus other real-world regimens in relapsed/refractory CLL (objective 3), adjusted HRs (95% CI) were 0.37 (0.22–0.63; p = 0.0003) for PFS and 0.53 (0.27–1.03; p < 0.0624) for OS. This adjusted analysis, based on nonrandomized patient data, suggests ibrutinib to be more effective than other commonly used regimens for CLL.

scholarly journals Acalabrutinib in Treatment-Naïve Chronic Lymphocytic Leukemia

Blood ◽  
2021 ◽  
Author(s):  
John C. Byrd ◽  
Jennifer A. Woyach ◽  
Richard R. Furman ◽  
Peter Martin ◽  
Susan O'Brien ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Phase 1 ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Second Primary ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Second Primary Cancers ◽  
Duration Of Response ◽  
Treatment Naïve

Acalabrutinib has demonstrated significant efficacy and safety in relapsed chronic lymphocytic leukemia (CLL). The efficacy and safety of acalabrutinib monotherapy was evaluated in a treatment-naïve CLL cohort of a single-arm phase 1/2 clinical trial (ACE-CL-001). Adults were eligible for enrollment if chemotherapy was declined or deemed inappropriate due to comorbidities (N = 99). Patient demographics included a median age of 64 years and 47% with Rai stage III/IV disease. Acalabrutinib was administered orally either 200 mg once daily (QD) or 100 mg twice daily (BID) until progression or intolerance. A total of 99 patients were treated; 57 (62%) had unmutated immunoglobulin heavy-chain variable gene (IGHV), and 12 (18%) had TP53 aberrations. After a median follow-up of 53 months, 85 patients remain on treatment; 14 patients discontinued treatment, mostly due to adverse events (AEs) (n = 6) or disease progression (n = 3). Overall response rate was 97% (90% partial response; 7% complete response), with similar outcomes among all prognostic subgroups. Due to improved trough BTK occupancy with BID dosing, all patients were transitioned to 100 mg BID. The median duration of response (DOR) was not reached; the 48-month DOR rate was 97% (95% confidence interval [CI], 90%, 99%). Serious AEs were reported in 38 patients (38%). AEs required discontinuation in 6 patients (6%) due to second primary cancers (n = 4) and infection (n = 2). Grade ≥3 events of special interest included infection (15%), hypertension (11%), bleeding events (3%), and atrial fibrillation (2%). The durable efficacy and long-term safety of acalabrutinib in this trial provide support for its use in clinical management of symptomatic, untreated CLL patients.

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