scholarly journals Optimizing Treatment Approaches for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

2021 ◽  
Vol 19 (11.5) ◽  
pp. 1339-1342
Author(s):  
Jennifer R. Brown
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Residual Disease ◽  
Patient Characteristics ◽  
Lymphocytic Leukemia ◽  
Continuous Treatment ◽  
Disease Relapse ◽  
Prior Therapy ◽  
Btk Inhibitor ◽  
Relapsed Disease ◽  
Choice Of Therapy

The choice of therapy for chronic lymphocytic leukemia (newly diagnosed as well as relapsed/refractory disease) depends on the disease (presence or absence of del(17p) or TP53 mutation) and patient characteristics (age, comorbidities, functional status and patient preference). Many patients can choose between continuous treatment with a Bruton’s tyrosine kinase (BTK) inhibitor or time-limited therapy with venetoclax/obinutuzumab. For patients with 17p deletions, the data support the use of continuous treatment with a BTK inhibitor, although these patients should also be referred to clinical trials evaluating novel combination therapy options with minimal residual disease monitoring. The choice of therapy for relapsed disease also depends on prior therapy and duration of response to prior therapy in addition to the disease and patient characteristics (as mentioned earlier). BTK inhibitor– or venetoclax-based regimens are recommended for patients experiencing relapse following chemoimmunotherapy. In the case of disease relapse following BTK inhibitor therapy, prospective data are available only for venetoclax-based regimens, whereas disease relapse (after a period of durable remission) following time-limited therapy with venetoclax-based regimens can be managed through re-treatment with venetoclax or a BTK inhibitor.

scholarly journals Updates in the Management of CLL/SLL: Management of Relapsed/Refractory Disease and the Role of Minimal Residual Disease

2021 ◽  
Vol 19 (5.5) ◽  
pp. 655-657
Author(s):  
Jennifer R. Brown
Keyword(s):  
Minimal Residual Disease ◽  
Residual Disease ◽  
Risk Profile ◽  
Lymphocytic Leukemia ◽  
Prospective Data ◽  
Prior Therapy ◽  
Btk Inhibitor ◽  
Choice Of Therapy ◽  
Minimal Residual

In relapsed chronic lymphocytic leukemia (CLL), the choice of therapy depends on the risk profile, prior therapy, and patient comorbidities. The first novel agent for patients who had previously received chemoimmunotherapy is typically a BTK inhibitor or combination venetoclax + rituximab. For patients with problematic comorbidities, however, a PI3K inhibitor can be used, but generally this is reserved for later lines of therapy. For those who stop ibrutinib due to adverse events, there are broad options but data are still limited. For those whose disease progresses on a BTK inhibitor, the only prospective data are for use of venetoclax. For patients who have been treated with venetoclax + rituximab and experience relapse, retreatment is a possibility if they have had a durable remission. Finally, undetectable minimal residual disease is strongly predictive of durability of response for time-limited regimens but not for continuous BTK inhibition, and is generally not indicated for monitoring patients.

scholarly journals Relapsed disease and aspects of undetectable MRD and treatment discontinuation

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 482-489
Author(s):  
Barbara Eichhorst ◽  
Moritz Fürstenau ◽  
Michael Hallek
Keyword(s):  
Residual Disease ◽  
Treatment Options ◽  
Predictive Marker ◽  
Optimal Choice ◽  
Lymphocytic Leukemia ◽  
Continuous Treatment ◽  
Combination Therapies ◽  
Frontline Therapy ◽  
Relapsed Disease ◽  
Minimal Residual

Abstract Continuous treatment vs fixed duration of monotherapies and combinations of targeted agents are treatment options in relapsed chronic lymphocytic leukemia. The optimal choice of relapse treatment is dependent on the prior frontline therapy, duration of remission after frontline, genetic markers, and patients’ condition, including age and comorbidities. Combination therapies may result in deep responses with undetectable minimal residual disease (uMRD). Although uMRD is an excellent predictive marker for disease progression, it is rarely used in clinical practice and needs additional evaluation in clinical trials before discontinuation of therapy should be guided according to uMRD.

scholarly journals Activity of Limited-Schedule Bendamustine and Methylprednisolone in Chronic Lymphocytic Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4700-4700
Author(s):  
Walter JR Quan ◽  
Meet Kadakia ◽  
Nithya Krishnan ◽  
Anthony Stack ◽  
Christy Rogers ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Median Duration ◽  
Conflicts Of Interest ◽  
Patient Characteristics ◽  
The United States ◽  
Median Number ◽  
Lymphocytic Leukemia ◽  
Prior Therapy ◽  
Trisomy 12 ◽  
Normal Cytogenetics

Abstract Bendamustine was approved by the United States Food and Drug Administration in 2008 for the treatment of Chronic Lymphocytic Leukemia (CLL). Corticosteroids have been administered in regimens with chemotherapy for CLL for more than 40 years. Despite this, the combination of Bendamustine and Methylprednisolone has not been explored in CLL. We describe our experience with Bendamustine 100 mg/m2 and Methylprednisolone 125 mg IV on days 1 and 2 and Peg-filgastrim 6 mg subcutaneously on day 3 every 28 days for 3-4 cycles in 12 patients with CLL. Cycles have been limited to attempt to prevent cumulative marrow toxicity due to Bendamustine. Patient characteristics: 7 males/5 females, median age-58, Binet stage B (8), C (2), A (2); ZAP70/CD38+ (5), Trisomy 12 (3), 13q- (2), normal cytogenetics (2); median ECOG status 1, no prior therapy in 8. Median number of cycles received = 3 (two received 4 cycles). Most common toxicities: nausea/emesis (5), fever/flu-like symptoms (4), arthralgia/myalgia (4). There have been no treatment-related deaths. One patient was briefly hospitalized for pneumonia. Complete responses have been seen in 6 patients (median duration = 50.7 months; range: 12.1+ to 87.3 months). Partial responses have been seen in 4 patients (median duration = 17.3+ months; range: 3.3 to 26.9+ months). The combination of Bendamustine and Methylprednisolone given in a limited schedule is well-tolerated and is active in CLL. Disclosures No relevant conflicts of interest to declare.

scholarly journals Fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy is highly effective treatment for relapsed patients with CLL

Blood ◽  
2011 ◽  
Vol 117 (11) ◽  
pp. 3016-3024 ◽  
Author(s):  
Xavier C. Badoux ◽  
Michael J. Keating ◽  
Xuemei Wang ◽  
Susan M. O'Brien ◽  
Alessandra Ferrajoli ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Final Analysis ◽  
Patient Characteristics ◽  
Lymphocytic Leukemia ◽  
Prior Exposure ◽  
Chromosome 17 ◽  
Prior Therapy ◽  
Previously Treated Patients ◽  
First Relapse ◽  
Previously Treated

Abstract Optimal management of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) is dictated by patient characteristics, prior therapy, and response to prior therapy. We report the final analysis of combined fludarabine, cyclophosphamide, and rituximab (FCR) for previously treated patients with CLL and identify patients who benefit most from this therapy. We explore efficacy of FCR in patients beyond first relapse, patients with prior exposure to fludarabine and alkylating agent combinations, and patients with prior exposure to rituximab. The FCR regimen was administered to 284 previously treated patients with CLL. Patients were assessed for response and progression by 1996 National Cancer Institute–Working Group (NCI-WG) criteria for CLL and followed for survival. The overall response rate was 74%, with 30% complete remission. The estimated median overall survival was 47 months and median progression-free survival for all patients was 21 months. Subgroup analyses indicated that the following patients were most suitable for FCR treatment: patients with up to 3 prior treatments, fludarabine-sensitive patients irrespective of prior rituximab exposure, and patients without chromosome 17 abnormalities. FCR is an active and well-tolerated therapy for patients with relapsed CLL. The addition of rituximab to FC improved quality and durability of response in this patient population.

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.

scholarly journals Advances in the biology and treatment of B-cell chronic lymphocytic leukemia

Blood ◽  
1995 ◽  
Vol 85 (2) ◽  
pp. 307-318 ◽  
Author(s):  
S O'Brien ◽  
A del Giglio ◽  
M Keating
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Residual Disease ◽  
Autologous Bone Marrow ◽  
Marrow Transplant ◽  
Lymphocytic Leukemia ◽  
Western Hemisphere ◽  
Molecular Heterogeneity ◽  
Prognostic Information ◽  
New Agents ◽  
History Of

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the western hemisphere. Diagnosis and staging of CLL are usually straightforward, but predicting an individual patient's prognosis is still a challenge. Cytogenetic abnormalities provide important prognostic information in CLL and may show its molecular heterogeneity. A search for oncogene abnormalities continues, although no consistent defects have been identified. New agents such as fludarabine produce high complete remission rates and have generated interest in earlier treatment as a first step in a potential cure. Fludarabine also makes autologous bone marrow transplant feasible as a consolidation therapy. Immunologic abnormalities and minimal residual disease persist in most patients in remission. Combining fludarabine with other active agents and devising effective postremission strategies may change the natural history of CLL.

How I treat chronic lymphocytic leukemia after venetoclax

Blood ◽  
2021 ◽  
Author(s):  
Thomas E Lew ◽  
Constantine S. Tam ◽  
John F. Seymour
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Residual Disease ◽  
Treatment Options ◽  
Cell Receptor ◽  
Resistance Mechanisms ◽  
Lymphocytic Leukemia ◽  
Bcl2 Family ◽  
Clinical Scenarios ◽  
Car T

Venetoclax-based regimens have expanded the therapeutic options for patients with chronic lymphocytic leukemia (CLL), frequently achieving remissions with undetectable measurable residual disease (uMRD) and facilitating time-limited treatment without utilizing chemotherapy. Although response rates are high and durable disease control is common, longer-term follow-up of patients with relapsed and refractory (RR) disease, especially in the presence of TP53 aberrations, demonstrates frequent disease resistance and progression. Although the understanding of venetoclax resistance remains incomplete, progressive disease (PD) is typified by oligoclonal leukemic populations with distinct resistance mechanisms, including BCL2 mutations, upregulation of alternative BCL2 family proteins and genomic instability. Although most commonly observed in heavily pre-treated patients with disease refractory to fludarabine and harboring complex karyotype (CK), Richter transformation (RT) presents a distinct and challenging manifestation of venetoclax resistance. For patients with progressive CLL after venetoclax, treatment options include B-cell receptor pathway inhibitors (BCRis), allogeneic stem cell transplantation (SCT), chimeric antigen receptor (CAR) T-cells, and venetoclax re-treatment for those with disease relapsing after time-limited therapy. However, data to inform clinical decisions for these patients are limited. We review the biology of venetoclax resistance and outline an approach to the common clinical scenarios encountered after venetoclax-based therapy that will increasingly confront practising clinicians.

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