The efficacy and safety of venetoclax therapy in elderly patients with relapsed, refractory chronic lymphocytic leukaemia

Eyre, Toby A.; Roeker, Lindsey E.; Fox, Christopher P.; Gohil, Satyen; Walewska, Renata; Walter, Henrik; Forconi, Francesco; Broom, Angus; Arumainathan, Arvind; Brander, Danielle M.; Allan, John N.; Schuster, Stephen J.; Hill, Brian T.; Lansigan, Frederick; Cheson, Bruce D.; Lamanna, Nicole; Coombs, Catherine C.; Barr, Paul M.; Skarbnik, Alan P; Shadman, Mazyar; Ujjani, Chaitra S.; Pearson, Laurie; Pagel, John M.; Jacobs, Ryan; Mato, Anthony R.

doi:10.1111/bjh.16271

Cited by 22 publications

(26 citation statements)

References 15 publications

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“…These seminal studies led to FDA and EMA approval of the following indications for the use of venetoclax in CLL: monotherapy in the presence of 17p deletion or TP53 mutation in patients who are unsuitable for or have failed a BCR inhibitor, or in the absence of 17p deletion or TP53 mutation in patients who have failed both chemoimmunotherapy and a BCR inhibitor; in combination with rituximab in patients who have received at least one prior therapy; in combination with obinutuzumab in previously untreated patients. In the real-life setting, large retrospective multicentre studies, conducted in the United States of America [ 52 , 53 ], the UK [ 54 , 55 ], and Italy [ 56 ] have demonstrated reassuringly similar efficacy and survival to trial outcomes. A safety analysis was performed in a retrospective cohort study including 297 all-age CLL venetoclax-treated patients outside of clinical trials [ 53 ].…”

Section: Therapeutic Approaches In Older And/or Unfit Patient Populationsmentioning

confidence: 99%

Treatment Options for Elderly/Unfit Patients with Chronic Lymphocytic Leukemia in the Era of Targeted Drugs: A Comprehensive Review

Fresa

Autore

Galli

et al. 2021

JCM

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Chronic lymphocytic leukemia (CLL) incidence increases with age reaching 37.9/100,000 in patients over 85 years. Although there is no standardized geriatric tool specifically validated for CLL, a correct framing of the fitness status is of critical importance to individualize treatment strategies. Based on the evidence available to date, frontline chemoimmunotherapy has an increasingly narrowing application, being eligible for candidacy only in elderly fit patients without or with minimal geriatric syndromes. On the other hand, treatment with BCR inhibitors, monotherapy, or in combination with anti-CD20 antibodies (e.g., obinutuzumab), must be preferred both for frontline and relapsed CLL not only in unfit patients, but also in fit patients with unmutated IGHV or harboring del(17p) and/or TP53 mutations/deletions. Second-generation inhibitors (e.g., acalabrutinib, zanubrutinib, pirtobrutinib) are novel compounds that, due to their better safety profile and different specificity, will help physicians overcome some of the safety issues and treatment resistances. In the era of targeted therapies, treatment decisions in elderly and/or unfit patients with CLL must be a balance between efficacy and safety, carefully evaluating comorbidities and geriatric syndromes to ensure the best approach to improve both quality of life and life expectancy.

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Section: Therapeutic Approaches In Older And/or Unfit Patient Populationsmentioning

confidence: 99%

Treatment Options for Elderly/Unfit Patients with Chronic Lymphocytic Leukemia in the Era of Targeted Drugs: A Comprehensive Review

Fresa

Autore

Galli

et al. 2021

JCM

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“…Neither FISH abnormalities nor complex karyotype was significant in predicting PFS or OS. Furthermore, exposure to multiple targeted therapies Refractory to or relapsed after FCR prior to targeted therapy 4 (13) Poor response to conventional chemotherapy 2 7Poor response to targeted therapy 3 (10) Richter transformation 3 (10) FCR, fludarabine, cyclophosphamide, and rituximab. *Missing data are excluded from the denominator in calculation of percentage.…”

Section: Clinical Outcome: Targeted Therapy Cohortmentioning

confidence: 99%

“…7 In addition, many high-risk patients discontinue targeted therapy due to the development of toxicity or eventually progress through all available agents. [7][8][9][10][11] For those patients who have exhausted all therapies, few treatment options are available and alloHCT remains the only established potentially curative therapeutic modality. Nonetheless, identification of patients who will most benefit from alloHCT and the optimal timing of alloHCT have been less clear in the era of targeted therapy.…”

Section: Introductionmentioning

confidence: 99%

Allogeneic hematopoietic cell transplantation after prior targeted therapy for high-risk chronic lymphocytic leukemia

et al. 2020

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Allogeneic hematopoietic cell transplantation (alloHCT) can cure previously treated high-risk chronic lymphocytic leukemia (CLL) patients if they are suitable for transplant through the graft-versus-leukemia effect. However, since the emergence of targeted therapies, the role of alloHCT for high-risk CLL is less clear. To address this question, we evaluated 108 high-risk CLL patients who underwent alloHCT from 2010 to 2018. Thirty patients from the period of 2013 to 2018 received targeted therapy prior to alloHCT. The median age for the targeted therapy cohort was 60 years (range, 30-71 years), and 20% and 73% had complete and partial remission, respectively: 76% had del(17p), 46.2% had 5 or more cytogenetic abnormalities, and 78.9% were IGHV unmutated. The median number of prior therapies was 4 (range, 1-9). With a median follow-up time of 36 months (range, 10-72 months), the 3-year overall (OS) and progression-free survival (PFS) were 87% and 69%, respectively. The 3-year cumulative incidence of nonrelapse mortality and relapse was 7% and 24%, respectively. For the control cohort of 78 patients who underwent alloHCT from 2010 to 2014 and received only chemoimmunotherapy prior to transplant, the 3-year OS and PFS were 69% and 58%, respectively. Patients treated with targeted therapy prior to alloHCT had a significantly higher number of circulating T and B cells and a lower ratio of CD4 regulatory T cells to CD4 conventional T cells early after transplant. In summary, despite multiple high-risk features, the clinical outcome of CLL patients who receive targeted therapy prior to transplant is excellent and alloHCT should be offered while the disease is under control.

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“…The most common adverse reaction is gastrointestinal symptoms. Due to the fact that high-dose venetoclax (1200mg daily) can cause serious gastrointestinal symptoms, 24 a dose of 400–800 mg/day is widely used when venetoclax is combined with other drugs. Other serious adverse reactions include pneumonia, febrile neutropenia, or autoimmune haemolytic anaemia.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Venetoclax Combined with Decitabine-Based Treatment for Heavily Pre-Treated Relapsed or Refractory AML Patients in a Real-World Setting

Tong

Zhao

et al. 2021

CMAR

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Purpose: We report the efficacy and safety of venetoclax plus decitabine-based treatment in heavily pre-treated relapsed or refractory acute myeloid leukaemia (RR-AML) in a realworld setting. Patients and Methods: There were 22 patients in this study and the median age was 47.5 (12-84) years old, including 11 males and 11 females. Among them, 8 patients were relapsed AML including 2 patients relapsed after HSCT and 14 patients with primary refractory AML including 4 secondary AML. The median number of cycles of previous chemotherapy was 4 (range, 2-10). Results: After a course of venetoclax plus decitabine-based treatment, 9 patients achieved complete remission (CR) and 1 patient achieved complete remission with incomplete haematological recovery (CRi). The overall response rate (ORR) was 45.5% and the CR rate was 40.9%, and the median time to reach CR/CRi was 21 (13-46) days. Four of the 10 CR/ CRi patients relapsed again, and the median time of relapse was 5 (1.0-24) months. The oneyear overall survival rate was 31.8%, and the median survival time was 6 months (95% CI, 1-9 months). The one-year overall survival rate of 10 CR/CRi patients was 59.1%, and the 12 NR patients was 10.4% (p=0.001). Nausea and vomiting occurred in 11 patients (50.0%). All patients had grade IV neutropenia and IV thrombocytopenia (100%). Pneumonia occurred in 14 patients (63.6%) and septicaemia occurred in 2 patients (9.0%). The cause of death in all patients was primary disease progression, and no patients died due to the side effects. Conclusion:The efficacy of venetoclax plus decitabine-based treatment in the real-world treatment of heavily pre-treated RR-AML is similar to that in clinical trials, and the side effects are controllable.

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The efficacy and safety of venetoclax therapy in elderly patients with relapsed, refractory chronic lymphocytic leukaemia

Cited by 22 publications

References 15 publications

Treatment Options for Elderly/Unfit Patients with Chronic Lymphocytic Leukemia in the Era of Targeted Drugs: A Comprehensive Review

Treatment Options for Elderly/Unfit Patients with Chronic Lymphocytic Leukemia in the Era of Targeted Drugs: A Comprehensive Review

Allogeneic hematopoietic cell transplantation after prior targeted therapy for high-risk chronic lymphocytic leukemia

Efficacy of Venetoclax Combined with Decitabine-Based Treatment for Heavily Pre-Treated Relapsed or Refractory AML Patients in a Real-World Setting

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