early relapse

Ibrutinib in the Treatment of Relapsed Chronic Lymphocytic Leukemia

NOVEL DRUGS , , ,

EA Stadnik, NS Timofeeva, VV Strugov, AYu Zaritskey

VA Almazov National Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341

For correspondence: Elena Aleksandrovna Stadnik, PhD, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341; Tel.: +7(921)575-54-55; e-mail: elena_stadnik@mail.ru

For citation: Stadnik EA, Timofeeva NS, Strugov VV, Zaritskey AYu. Ibrutinib in the Treatment of Relapsed Chronic Lymphocytic Leukemia. Clinical oncohematology. 2018;11(1):42–9.

DOI: 10.21320/2500-2139-2018-11-1-42-49

ABSTRACT

Aim. To estimate ibrutinib efficacy in the treatment of first early CLL relapses and in patients with ≥ 2 lines of preceding therapy. Analysis of treatment results in patients with del(17p) and monitoring of minimal residual disease (MRD) and ibrutinib safety profile.

Materials & Methods. The analysis included the results of ibrutinib treatment in 31 patients with CLL. Twenty eight patients were treated by bendamustine and fludarabine containing regimens. The median prior treatment lines were 2 (range 1–10). The indications for the treatment initiation were the first early relapse in 51 % of cases (n = 16) and a relapse after 2 and more lines of therapy in 49 % of cases (n = 15). Ibrutinib was administered in mono- (n = 15) and combined therapy (n = 14) as well as in the R-BAC scheme (n = 2). Using FISH analysis del(17p) was found in 9 patients (34 %).

Results. Within the median follow up of 18 months (range 7–42+) the overall survival (OS) rate was reported to be 87 %, and the progression-free survival (PFS) rate was 77 %. The maximum MRD after a year of ibrutinib treatment was observed in case of combination with immunochemotherapy (e.g., R-BAC). Within the period of 18 months OS rate was 100 %, in the patient group with first early relapses and 66 % in the group with a relapse after 2 and more therapy lines (p = 0.02). Within the same examination period PFS was significantly higher (94 %) in the patient group with first early relapses compared to the previously treated patients (60 %) (p = 0.034). The most common adverse events were grade 1–2 purpura (30 %), grade 1–2 diarrhea (10 %), atrial fibrillation paroxysms (10 %) and arterial hypertension (10 %). Severe infectious complications registered in 6 % (n = 3) patients were successfully solved in the course of combined antibacterial and antimycotic treatment.

Conclusion. Ibrutinib was shown to be effective drug for treatment of relapsed CLL. The OS and PFS values were more favourable in patients with first early relapses compared to the patients with relapses after ≥ 2 lines of therapy prior to ibrutinib treatment. The maximum elimination of the tumor clone was observed after combined ibrutinib/immunochemotherapy treatment. The tolerance of ibrutinib was reported to be satisfactory with acceptable toxicity profile. No mortality due to infection complications was observed.

Keywords: chronic lymphocytic leukemia, first early relapse, del(17p), ibrutinib, minimal residual disease.

Received: August 20, 2017

Accepted: November 16, 2017

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