Long-term real-world results of ibrutinib therapy in patients with relapsed or refractory chronic lymphocytic leukemia: 30-month follow up of the Swedish compassionate use cohort

Winqvist, Maria; Andersson, Per‐Ola; Asklid, Anna; Karlsson, Karin; Karlsson, Claes; Lauri, Birgitta; Lundin, Jeanette; Mattsson, Mattias; Norin, Stefan; Sandstedt, Anna; Rosenquist, Richard; Späth, Florentin; Hansson, Lotta; Österborg, Anders

doi:10.3324/haematol.2018.198820

Cited by 53 publications

(57 citation statements)

References 8 publications

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“…However, we found 39.0% of all patients had at least one grade ≥3 infection, which is higher than reported in the RESONATE study (24%), 4 but in line with the long‐term follow‐up Swedish real‐world study reporting 51% of the patients with a grade 3‐4 infection. 23 This illustrates the importance of real‐world studies, since the results likely reflect how older and more frail patients included in real‐world studies are at higher risk of infections. We further demonstrated that the rate of infections was highest during the first 6 months, similar to what has been reported in previous clinical trials 24,25 .…”

Section: Discussionmentioning

confidence: 99%

Real‐world outcomes for 205 patients with chronic lymphocytic leukemia treated with ibrutinib

Aarup

Rotbain

Enggaard

et al. 2020

European J of Haematology

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Ibrutinib has now been approved for treatment of chronic lymphocytic leukemia (CLL) in both front-line setting and as later-line treatment. However, knowledge about the outcomes and adverse events (AE) among patients at a population-based level is still limited. Objectives: To report outcomes and AEs in a population-based cohort treated with ibrutinib outside clinical trials. Methods: We conducted a multicenter, retrospective cohort study including all patients with CLL treated with ibrutinib. Results: In total, 205 patients were included of whom 39 (19%) were treatment-naïve. The median follow-up was 21.4 months (interquartile range (IQR), 11.9, 32.8), the estimated overall survival at 12 months was 88.8% (95% confidence interval (CI); 84.3%, 93.3%), and the estimated progression-free survival at 12 months was 86.3% (95% CI; 81.3%, 91.2%). During follow-up, 200 (97.6%) patients had at least one AE and 100 (48.8%) patients had at least one grade ≥3 AE. Eighty-six patients (42.0%) discontinued ibrutinib, hereof 47 (54.7%) due to AEs and 19 (22.1%) had progression of CLL or Richter transformation. Conclusions: In our study, we find comparable, though slightly inferior, overall, and progression-free survival, and discontinuation due to toxicity was higher compared with clinical trials. Patient training and information may improve treatment adherence outside clinical trials.

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Section: Discussionmentioning

confidence: 99%

Real‐world outcomes for 205 patients with chronic lymphocytic leukemia treated with ibrutinib

Aarup

Rotbain

Enggaard

et al. 2020

European J of Haematology

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“…Multiple studies have described dose reductions in approximately 15%–30% of ibrutinib‐treated patients [2–4, 18]. Across varied patient cohorts evaluating dose reductions, consistent findings of no significant differences in PFS or OS have been reported [3, 18–22]. Temporary interruptions in treatment appear more frequent, with estimates ranging from 35% of patients in clinical practice [4] to 65% of those treated on clinical trials [2].…”

Section: Discussionmentioning

confidence: 94%

Disease Flare During Temporary Interruption of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia

et al. 2020

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Background Approximately 25% of patients with chronic lymphocytic leukemia (CLL) experience a flare of disease following ibrutinib discontinuation. A critical question is whether this phenomenon may also occur when ibrutinib is temporarily held. This study aimed to determine the frequency and characteristics of disease flares in this setting and assess risk factors and clinical outcomes. Materials and Methods We identified all patients with CLL seen at Mayo Clinic between October 2012 and March 2019 who received ibrutinib. Temporary interruptions in treatment and associated clinical findings were ascertained. Results Among the 372 patients identified, 143 (38%) had at least one temporary interruption (median 1 hold, range 1–7 holds) in treatment. The median duration of interruption was 8 days (range 1–59 days) and the most common indication was periprocedural. Among the 143 patients with ≥1 hold, an associated disease flare was seen in 35 (25%) patients: mild (constitutional symptoms only) in 21 patients and severe (constitutional symptoms with exam/radiographic findings or laboratory changes) in 14 patients. Disease flare resolved with resuming ibrutinib in all patients. Predictive factors of disease flare included progressive disease at time of hold and ≥ 24 months of ibrutinib exposure. The occurrence of disease flare with an ibrutinib hold was associated with shorter event‐free survival (hazard ratio 2.3; 95% confidence interval 1.3–4.1; p = .007) but not overall survival. Conclusion Temporary interruptions in ibrutinib treatment of patients with CLL are common, and one quarter of patients who held ibrutinib in this study experienced a disease flare. Resolution with resuming ibrutinib underscores the importance of awareness of this phenomenon for optimal management. Implications for Practice Ibrutinib is a very effective treatment for chronic lymphocytic leukemia (CLL) but needs to be taken continuously. Side effects, such as increased bleeding risk with procedures, require temporary interruptions in this continuous treatment. Rapid CLL progression following ibrutinib discontinuation has been increasingly recognized. This study demonstrates that similar flares in disease signs or symptoms may occur during ibrutinib holds as well. Importantly, management with restarting ibrutinib led to quick clinical improvement. Awareness of this phenomenon among clinicians is critical to avoid associated patient morbidity and premature cessation of effective treatment with ibrutinib if the flare is misidentified as true progression of disease.

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“…Clinical trials and real-world data on ibrutinib treatment in frontline and relapse-refractory settings in CLL/SLL patients showed a favorable safety profile [4,13,[15][16][17]51,[53][54][55][56][57][58][59][60][61][62]. The prevailing ibrutinib-related adverse events included diarrhea (up to 60%), arthralgia (up to 40%), rash (up to 25%), infections mainly of the upper respiratory tract (up to 35%) and mild hematological toxicity occurred in up to 60% of patients.…”

Section: Ibrutinib Adverse Eventsmentioning

confidence: 99%

“…Although ibrutinib treatment was well tolerated, some unexpected adverse events, probably due to off-target activity, have also been reported and included mainly atrial fibrillation and hemorrhagic complications [4,13,[15][16][17]51,[53][54][55][56][57][58][59][60][61][62]. Atrial fibrillation occurs in approximately 6-16% patients, predominantly in the first 6 months of treatment and is mostly grade 1-2 [63,64].…”

Section: Ibrutinib Adverse Eventsmentioning

confidence: 99%

Overcoming Ibrutinib Resistance in Chronic Lymphocytic Leukemia

Puła

Gołoś

Górniak

et al. 2019

Cancers

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Ibrutinib is the first Bruton's tyrosine kinase (BTK) inhibitor, which showed significant clinical activity in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) patients regardless of cytogenetic risk factors. Recent results of phase III clinical trials in treatment-naïve CLL patients shift the importance of the agent to frontline therapy. Nevertheless, beside its clinical efficacy, ibrutinib possesses some off-target activity resulting in ibrutinib-characteristic adverse events including bleeding diathesis and arrhythmias. Furthermore, acquired and primary resistance to the drug have been described. As the use of ibrutinib in clinical practice increases, the problem of resistance is becoming apparent, and new methods of overcoming this clinical problem arise. In this review, we summarize the mechanisms of BTK inhibitors' resistance and discuss the post-ibrutinib treatment options.

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Long-term real-world results of ibrutinib therapy in patients with relapsed or refractory chronic lymphocytic leukemia: 30-month follow up of the Swedish compassionate use cohort

Abstract: Long-term real-world results of ibrutinib therapy in patients with relapsed or refractory chronic lymphocytic leukemia: 30-month follow up of the Swedish compassionate use cohort LETTERS TO THE EDITOR

Cited by 53 publications

References 8 publications

Real‐world outcomes for 205 patients with chronic lymphocytic leukemia treated with ibrutinib

Real‐world outcomes for 205 patients with chronic lymphocytic leukemia treated with ibrutinib

Disease Flare During Temporary Interruption of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia

Overcoming Ibrutinib Resistance in Chronic Lymphocytic Leukemia

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