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Clinical Trial
. 2018 Aug;182(4):504-512.
doi: 10.1111/bjh.15421. Epub 2018 Jun 5.

Evaluation of 230 patients with relapsed/refractory deletion 17p chronic lymphocytic leukaemia treated with ibrutinib from 3 clinical trials

Jeffrey Jones  1 , Anthony Mato  2   3 , Steven Coutre  4 , John C Byrd  1 , Richard R Furman  5 , Peter Hillmen  6 , Anders Osterborg  7 , Constantine Tam  8 , Stephan Stilgenbauer  9 , William G Wierda  10 , Nyla A Heerema  1 , Karl Eckert  11 , Fong Clow  11 , Cathy Zhou  11 , Alvina D Chu  11 , Danelle F James  11 , Susan M O'Brien  12
Affiliations
Clinical Trial

Evaluation of 230 patients with relapsed/refractory deletion 17p chronic lymphocytic leukaemia treated with ibrutinib from 3 clinical trials

Jeffrey Jones et al. Br J Haematol. 2018 Aug.

Abstract

Patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) with deletion 17p [del(17p)] have poor outcomes with chemoimmunotherapy. Ibrutinib is indicated for the treatment of CLL/SLL, including del(17p) CLL/SLL, and allows for treatment without chemotherapy. This integrated analysis was performed to evaluate outcomes in 230 patients with relapsed/refractory del(17p) CLL/SLL from three ibrutinib studies. With a median of 2 prior therapies (range, 1-12), 18% and 79% of evaluable patients had del(11q) or unmutated IGHV, respectively. With a median follow-up of 28 months, overall response rate was 85% and estimated 30-month progression-free and overall survival rates were 57% [95% confidence interval (CI) 50-64] and 69% (95% CI 61-75), respectively. Patients with normal lactate dehydrogenase or no bulky disease had the most favourable survival outcomes. Sustained haematological improvements in haemoglobin, platelet count and absolute neutrophil count occurred in 61%, 67% and 70% of patients with baseline cytopenias, respectively. New onset severe cytopenias and infections decreased in frequency over time. Progression-free and overall survival with ibrutinib surpass those of other therapies for patients with del(17p) CLL/SLL. These results provide further evidence of the robust clinical activity of ibrutinib in difficult-to-treat CLL/SLL populations.

Keywords: 17p deletion; BTK inhibitor; chronic lymphocytic leukaemia; ibrutinib.

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Figures

Figure 1
Figure 1
Overall response rates (ORR) as assessed by investigator. Rates are reported for each clinical trial and for the entire study population. CR, complete response; CRi, CR with incomplete bone marrow recovery; PR, partial response; PR‐L, PR with lymphocytosis; nPR, nodular PR. *CR = CR + CRi.
Figure 2
Figure 2
Survival outcomes. (A) Progression‐free survival and (B) overall survival at a median follow‐up of 28 months.
Figure 3
Figure 3
Survival outcomes for patients with (n = 14) or without (n = 7) complex karyotype in the PCYC‐1102/1103 Study. (A) Progression‐free survival and (B) overall survival. del(17p), deletion of chromosome 17p; CK, complex karyotype.
Figure 4
Figure 4
Onset of grade ≥3 adverse events of clinical interest over time.
See this image and copyright information in PMC

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