ASH Clinical News ACN_4.5_FULL_ISSUE_DIGITAL - Page 18

Written in Featured research from recent issues of Blood PAPER SPOTLIGHT Five-Year Follow-Up Shows Response to Ibrutinib Deepens Over Time for CLL Patients Treatment with continuous, single-agent ibrutinib led to durable responses in patients with chronic lymphocytic leukemia (CLL), even among previously untreated patients, patients older than 65 years, and those with TP53 mutations. “In most cancers, with the notable exception of chronic myeloid leukemia, single-agent therapy is limited by the rapid emergence of drug resistance,” wrote Inhye E. Ahn, MD, of the National Heart, Lung, and Blood Institute and co-authors in a recent study published in Blood. “Our data with extended follow-up of patients on ibrutinib suggests that a large proportion of [patients with] CLL achieve durable disease control on single- agent ibrutinib, with excellent tolerability.” “With continuing the treat- ment for almost five years, not only were the remissions lasting, but, in many cases, they improved from partial to complete remis- sions (CR), including some patients who achieved minimal residual disease (MRD) negativ- ity,” Kanti Rai, MD, professor at Donald and Barbara Zucker School of Medicine at Hofstra/ Northwell Health, told ASH Clinical News when asked for comments on the study’s find- ings. (Read more from Dr. Rai in “Perspectives” at the end of this article.) The open-label, single-center study enrolled 86 patients (me- dian age = 66 years; range = 33- 85 years) between December 2011 and January 2014. Participants had CLL or small lymphocytic lymphoma that required therapy, an Eastern Cooperative Oncology Group performance status score of ≤2, neutrophil count ≥500/µL, and platelet count ≥30,000/µL. 16 ASH Clinical News Most patients were treatment- naïve (n=53; 61.6%), had advanced disease (Rai stage III/IV; n=58; 67.4%), and had unmutated immunoglobulin heavy-chain variable region gene (IGHV; n=57; 66.3%). The 33 patients (38.4%) with relapsed/refractory disease had been treated with up to seven prior regimens. Patients received ibrutinib 420 mg once-daily until disease progres- sion or unacceptable toxicity. As of December 31, 2017 (data cutoff), 49 patients (57%) remained on study after a median of 4.8 years (range = 4-6 years). Four patients (4.7%) died because of infection (n=3) and cardiac events (n=1). Twenty-five patients discontinued ibrutinib because of progressive disease (23.3%) or ad- verse events (AEs; 5.8%). Six pa- tients (7.0%) withdrew for various other reasons, and two patients did not meet the eligibility criteria and were excluded. AEs that led to treatment discontinuation included asymp- tomatic interstitial pulmonary TABLE 1. infiltrates, progressive multi- focal leukoencephalopathy, and persistent grade 3 diarrhea with biopsy-confirmed microscopic colitis (n=1 for each). Two patients (2.3%) discontinued because of second malignancies requiring systemic therapy. Nine patients (10.5%) required ibrutinib dose reductions. “The safety profile of con- tinuous therapy with ibrutinib for [more than] five years was simi- lar to what has been reported with shorter treatment duration,” the researchers reported. “No new safety signals emerged, and most AEs were grade 1 or 2 and transient.” The most common treatment-related grade 3 or 4 hematologic AEs were neutrope- nia (n=33; 38.4%), thrombocyto- penia (n=13; 15.1%), and a