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 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.

Allotransplantation for chronic lymphocytic leukemia

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 602-609 ◽  
Author(s):  
Peter Dreger
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Immune Modulation ◽  
Residual Disease ◽  
Treatment Strategies ◽  
Treatment Resistance ◽  
Lymphocytic Leukemia ◽  
Successful Outcome ◽  
Mortality And Morbidity ◽  
Poor Risk ◽  
Leukemic Clone

AbstractEfforts to develop curative treatment strategies for chronic lymphocytic leukemia (CLL) in recent years have focused on allogeneic stem cell transplantation (alloSCT). The crucial anti-leukemic principle of alloSCT in CLL appears to be the immune-mediated anti-host activities conferred with the graft (graft-versus-leukemia effects, GVL). Evidence for GVL in CLL is provided by studies analyzing the kinetics of minimal residual disease on response to immune modulation after transplantation, suggesting that GVL can result in complete and durable suppression of the leukemic clone. AlloSCT from matched related or unrelated donors can overcome the treatment resistance of poor-risk CLL, ie, purine analogue refractory disease and CLL with del 17p-. Even with reduced-intensity conditioning, alloSCT in CLL is associated with significant mortality and morbidity due to graft-versus-host disease, which has to be weighed against the risk of the disease when defining the indication for transplantation. Therefore, it can be regarded as a reasonable treatment option only for eligible patients who fulfill accepted criteria for poor-risk disease. If alloSCT is considered, it should be performed before CLL has advanced to a status of complete refractoriness to assure an optimum chance for a successful outcome. Prospective trials are underway to prove whether allo-SCT can indeed change the natural history of poor-risk CLL.

scholarly journals Mcl-1 expression predicts progression-free survival in chronic lymphocytic leukemia patients treated with pentostatin, cyclophosphamide, and rituximab

Blood ◽  
2009 ◽  
Vol 113 (3) ◽  
pp. 535-537 ◽  
Author(s):  
Farrukh T. Awan ◽  
Neil E. Kay ◽  
Melanie E. Davis ◽  
Wenting Wu ◽  
Susan M. Geyer ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Residual Disease ◽  
Treatment Strategies ◽  
Myeloid Cell ◽  
Progression Free Survival ◽  
Poor Response ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Phase 2 Study ◽  
Significant Difference

Abstract Myeloid cell leukemia-1 (Mcl-1) is an antiapoptotic member of the Bcl-2 protein family. Increased Mcl-1 expression is associated with failure to achieve remission after treatment with fludarabine and chlorambucil in patients with chronic lymphocytic leukemia (CLL). However, the influence of Mcl-1 expression has not been examined in CLL trials using chemoimmunotherapy. We investigated Mcl-1 protein expression prospectively as part of a phase 2 study evaluating the efficacy of pentostatin, cyclophosphamide, and rituximab in patients with untreated CLL. No significant difference by Mcl-1 expression was noted in pretreatment or response parameters. However, in patients with higher Mcl-1 expression, both minimal residual disease-negative status and progression-free survival was found to be significantly reduced (57% vs 19%, P = .01; 50.8 vs 18.7 months; P = .02; respectively). Mcl-1 expression may therefore be useful in predicting poor response to chemoimmunotherapy. These findings further support pursuing treatment strategies targeting this important antiapoptotic protein. (Because the trials described were conducted before the requirement to register them was implemented, they are not registered in a clinical trial database.)

Tailored Treatment Strategies for Chronic Lymphocytic Leukemia in a Rapidly Changing Era

2019 ◽  
pp. 487-498
Author(s):  
Danielle Brander ◽  
Prioty Islam ◽  
Jacqueline C. Barrientos
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Residual Disease ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Disease Assessment ◽  
Clinical Endpoints ◽  
Tailored Treatment ◽  
Signaling Inhibitors

The treatment landscape for chronic lymphocytic leukemia (CLL) is rapidly evolving, with multiple agents recently approved. They include a glycoengineered monoclonal antibody (obinutuzumab), B-cell receptor signaling inhibitors (ibrutinib, idelalisib, and duvelisib), and the BCL-2 inhibitor (venetoclax). These compounds are dramatically changing the natural course of the disease. Nonetheless, despite improved survival rates, particularly in higher-risk disease (older adults, patients with unmutated IGHV, del(11q), and del(17p)/ TP53 mutated), there is still room for progress. Given the panoply of highly effective therapies commercially available, it is important to define a tailored treatment strategy for this heterogeneous condition that considers balance of treatment efficacy versus toxicity or tolerance. This article summarizes the most promising clinical advances by reviewing the data from recent clinical trials and discussing meaningful clinical endpoints, including the role of minimal residual disease assessment. The recent development of therapies targeting dysregulated pathways is revolutionary and may ultimately lead us to not only achieve prolonged remission durations but also envision the possibility of a functional cure for a larger population of patients.

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 Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia

Blood ◽  
2006 ◽  
Vol 109 (2) ◽  
pp. 405-411 ◽  
Author(s):  
Neil E. Kay ◽  
Susan M. Geyer ◽  
Timothy G. Call ◽  
Tait D. Shanafelt ◽  
Clive S. Zent ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphocytic Leukemia ◽  
Clinical Activity ◽  
Hematologic Toxicity ◽  
Color Flow ◽  
Significant Clinical Activity ◽  
Minimal Residual

Abstract Building on the prior work of use of pentostatin in chronic lymphocytic leukemia (CLL), we initiated a trial of combined pentostatin (2 mg/m2), cyclophosphamide (600 mg/m2), and rituximab (375 mg/m2) for 65 symptomatic, previously untreated patients. Of 64 evaluable patients, 34 (53%) were high Rai risk, 71% were nonmutated for the immunoglobulin heavy-chain variable region gene, 34% were CD38+, and 34% were ZAP-70+. Thirty patients (52%) had one anomaly detected by fluorescence in situ (FISH) hybridization, and 21 (36%) had complex FISH defects. Thirty-eight patients (58%) had grade 3+ hematologic toxicity but minimal transfusion needs and no major infections. Responses occurred in 58 patients (91%), with 26 (41%) complete responses (CRs), 14 (22%) nodular partial responses (nodular PRs), and 18 (28%) partial responses (PRs). Many patients with a CR also lacked evidence of minimal residual disease by 2-color flow cytometry. Examination of prognostic factors demonstrated poor response in the 3 patients with del(17p). In contrast, we found this regimen was equally effective in young versus older (> 70 years) patients and in del(11q22.3) versus other favorable prognostic factors. Thus, this novel regimen of pentostatin, cyclophosphamide, and rituximab for previously untreated patients with CLL demonstrated significant clinical activity despite poor risk-based prognoses, achievement of minimal residual disease in some, and modest toxicity.

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