Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study

Burger, Jan A.; Barr, Paul M.; Robak, Tadeusz; Owen, Carolyn; Ghia, Paolo; Tedeschi, Alessandra; Bairey, Osnat; Hillmen, Peter; Coutre, Steven; Devereux, Stephen; Grosicki, Sebastian; McCarthy, Helen; Simpson, David; Offner, Fritz; Moreno, Carol; Dai, Sandra; Lal, Indu; Dean, James P.; Kipps, Thomas J.

doi:10.1038/s41375-019-0602-x

Cited by 377 publications

(373 citation statements)

References 35 publications

Supporting

Mentioning

336

Contrasting

Unclassified

Order By: Relevance

“…33 Finally, the prevalence of adverse events generally improved with time on treatment. 33 Results of the PCYC112 and RESONATE 2 trials (summarized in Table 1), coupled with studies demonstrating improved clinical outcomes in elderly patients with treatment-naïve disease using chemoimmunotherapy compared with chemotherapy alone, 30,32 prompted trials to evaluate the safety and efficacy of ibrutinib in combination with anti-CD20 monoclonal antibodies.…”

Section: Ibrutinib Monotherapymentioning

confidence: 97%

“…Second, the ORR to ibrutinib improved with time (ORR 86% after median follow up of 18.4 months versus 92% after median follow up of 60 months). 29,33 Third, the depth of response to ibrutinib improved with time (CR rate 4% after median follow up 18.4 months versus 30% after median 60 months). 29,33 Fourth, ibrutinib was generally well tolerated, as supported by the rate of discontinuation due to adverse events of 21% after 60 months of follow up.…”

Section: Ibrutinib Monotherapymentioning

confidence: 99%

“…29,33 Third, the depth of response to ibrutinib improved with time (CR rate 4% after median follow up 18.4 months versus 30% after median 60 months). 29,33 Fourth, ibrutinib was generally well tolerated, as supported by the rate of discontinuation due to adverse events of 21% after 60 months of follow up. 33 Finally, the prevalence of adverse events generally improved with time on treatment.…”

Section: Ibrutinib Monotherapymentioning

confidence: 99%

“…chlorambucil) given the proven superiority of combination chlorambucil plus anti-CD20 monoclonal antibodies over chlorambucil alone in this patient population. [30][31][32] Extended follow-up studies of RESONATE 2 have since been published, 33,34 and they demonstrated several important features of ibrutinib therapy pertinent to elderly patients. First, responses with ibrutinib were durable (estimated PFS rate of 70% at 60 months in the ibrutinib arm compared with 12% in the chlorambucil arm).…”

Section: Ibrutinib Monotherapymentioning

confidence: 99%

See 3 more Smart Citations

BTK inhibitors and anti-CD20 monoclonal antibodies for treatment-naïve elderly patients with CLL

Rogers

Woyach

2020

Therapeutic Advances in Hematology

View full text Add to dashboard Cite

Older patients account for the majority of patients with chronic lymphocytic leukemia (CLL), and so strategies for managing CLL in this population is of upmost importance. Inhibition of Bruton’s tyrosine kinase (BTK) has been a successful therapeutic strategy in CLL, and the first-generation BTK inhibitor ibrutinib has been shown to be superior to standard chemoimmunotherapy in multiple studies specifically targeting older patients. A second-generation BTK inhibitor, acalabrutinib, has also been studied in CLL, and has recently been granted breakthrough designation by the United States Food and Drug Administration. One ongoing question is whether the addition of anti-CD20 monoclonal antibodies improve response or response durability with BTK inhibitors. In this review, we will discuss clinical trials of ibrutinib and acalabrutinib in older patients with CLL, and the possible contributions of anti-CD20 antibodies to these therapies.

show abstract

Section: Ibrutinib Monotherapymentioning

confidence: 97%

Section: Ibrutinib Monotherapymentioning

confidence: 99%

Section: Ibrutinib Monotherapymentioning

confidence: 99%

Section: Ibrutinib Monotherapymentioning

confidence: 99%

See 2 more Smart Citations

BTK inhibitors and anti-CD20 monoclonal antibodies for treatment-naïve elderly patients with CLL

Rogers

Woyach

2020

Therapeutic Advances in Hematology

View full text Add to dashboard Cite

show abstract

“…Several trials challenging this with the initiation of ibrutinib at diagnosis in patients without an indication to treat but high-risk disease are active, with results due to be reported in mid-2020 or in ongoing recruitment [72,73]. Additionally, longer term follow-up in patients treated with small molecule inhibitors is required to see if the achievement of MRD negativity improves survival as seen with FCR-it is likely that monitoring MRD will become more common place in CLL, as it is already in other haematological malignancies [74]. The results of a multicentre phase 1/2 trials establishing the maximum tolerated dose of alcalabrutinib-a BTK inhibitor with higher specificity and lower reversibility than ibrutinib-are due to be published in early 2021 indicating that with time, we will likely see an increase in the number of available drugs within the classes of small molecule inhibitors already established [75].…”

Section: Conclusion-the Future Of Cll Treatmentmentioning

confidence: 99%

Chronic Lymphocytic Leukaemia in 2020: the Future Has Arrived

2020

View full text Add to dashboard Cite

Purpose of Review Chronic lymphocytic leukaemia is now recognised as a heterogenous disease with a variety of clinical outcomes. Here we summarise the way it is currently stratified according to genetic risk and patient characteristics and the treatment approaches used for these different subgroups. Recent Findings Certain patients appear to sustain MRD negativity after combination chemoimmunotherapy, leading to the suggestion that their CLL may be cured. However, 17p-deleted, p53-mutated or IGHV-UM subgroups are generally resistant to FCR, and much better responses are seen with ibrutinib and venetoclax, frequently inducing MRD negativity that hopefully will be translated into durable remissions. Summary Small molecule inhibitors have already revolutionised CLL treatment. Going forward, we anticipate their use in the majority of patients, early after diagnosis and with curative intent.

show abstract

Ibrutinib Plus Venetoclax for First-line Treatment of Chronic Lymphocytic Leukemia

et al. 2021

Self Cite

View full text Add to dashboard Cite

IMPORTANCEOral targeted therapies have advanced the treatment of chronic lymphocytic leukemia (CLL). These therapies include Bruton tyrosine kinase inhibitors, used as monotherapy, and the Bcl-2 inhibitor venetoclax, typically combined with the CD20 monoclonal antibody. Preclinical studies have shown synergy between Bruton tyrosine kinase inhibitors and the Bcl-2 inhibitor venetoclax.OBJECTIVE To examine the rate of complete remission, complete remission with incomplete count recovery, and bone marrow-undetectable measurable residual disease (U-MRD) after treatment with the combination of ibrutinib and venetoclax. DESIGN, SETTING, AND PARTICIPANTSA single-center, phase 2 nonrandomized trial enrolled patients from August 17, 2016, to June 5, 2018. Participants included previously untreated patients with CLL who met International Workshop on CLL 2008 criteria for treatment indication. Patients were required to have at least 1 of the following features: del(17p), TP53-mutated CLL, del(11q), unmutated immunoglobulin heavy-chain variable gene, or age 65 years or older. INTERVENTIONS Therapy consisted of ibrutinib, 420 mg/d, monotherapy for 3 cycles, thereafter combined with venetoclax (standard weekly dose ramp-up to 400 mg/d) for a total of 24 cycles of combination treatment. Responses were assessed at serial points according to International Workshop on CLL 2008 criteria. Measurable residual disease (MRD) was assessed by multicolor flow cytometry with a sensitivity of 10 −4 . MAIN OUTCOMES AND MEASURES Outcomes included complete remission, complete remission with incomplete count recovery, and bone marrow U-MRD rate.RESULTS Eighty patients (57 [71%] men) were treated; median age was 65 years (range, 26-83 years). The median follow-up for all 80 patients was 38.5 months (range, 5.6-51.1 months). Five patients discontinued the study during the ibrutinib monotherapy phase; the remaining 75 patients received combination therapy. On an intent-to-treat analysis of combined treatment, 45 (56%) patients achieved bone marrow U-MRD remission at 12 cycles and 53 (66%) patients achieved bone marrow U-MRD remission at 24 cycles. Overall, 60 (75%) patients achieved bone marrow U-MRD remission as their best response. Responses were seen across all high-risk subgroups, independent of the immunoglobulin heavy-chain variable gene mutation status, fluorescence in situ hybridization category, or TP53 mutation. The 3-year progression-free survival was 93%, and 3-year overall survival was 96%. No patient had CLL progression; 2 patients developed Richter transformation. CONCLUSIONS AND RELEVANCEThe findings of this study suggest that combination therapy with ibrutinib and venetoclax might be beneficial for previously untreated patients with CLL. Remissions appeared to be durable during a follow-up of more than 3 years, with activity seen across high-risk disease subgroups, including those with del(17p)/TP53-mutated CLL.

show abstract

Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study

Cited by 377 publications

References 35 publications

BTK inhibitors and anti-CD20 monoclonal antibodies for treatment-naïve elderly patients with CLL

BTK inhibitors and anti-CD20 monoclonal antibodies for treatment-naïve elderly patients with CLL

Chronic Lymphocytic Leukaemia in 2020: the Future Has Arrived

Ibrutinib Plus Venetoclax for First-line Treatment of Chronic Lymphocytic Leukemia

Contact Info

Product

Resources

About