Publication Date:
2018-11-29
Description:
Background : In 2014, a planned interim analysis of an open-label, two-arm, randomized, phase III study of ofatumumab (OFA) vs physicians' choice (PC) treatment (most patients received rituximab-, alemtuzumab-, alkylator-, or fludarabine-based therapies) in patients with bulky fludarabine-refractory chronic lymphocytic leukemia (BFR CLL) was performed to assess the effectiveness of OFA in the time-period prior to administering small molecule kinase inhibitors. The study did not meet its primary endpoint of progression-free survival (PFS) as assessed by the independent review committee (median PFS 5.4 months vs 3.6 months; hazard ratio [HR]=0.79, 95% confidence interval [CI]: 0.50, 1.24; p=0.268). Here, we report the 5-year follow-up of the study. Methodology : Patients with BFR CLL who required therapy and had received at least 2 prior therapies were randomized (2:1) to receive either OFA or PC therapy. Eligible participants were stratified based on del (17p) status, the Eastern Cooperative Oncology Group (ECOG) Performance Status (0, 1, or 2), and fludarabine-refractory status (no response vs 15% in either) were neutropenia (21% vs 19%), pneumonia (18% vs 19%), and anemia (9% vs 19%), respectively. Grade 3, 4, and 5 AEs (〉10%) in the OFA and PC arms were neutropenia (17% vs 16%), pneumonia (14% vs 9%), febrile neutropenia (9% vs 12%), and anemia (6% vs 14%), respectively. Serious AEs (≥5%) in the OFA and PC arms were pneumonia (13% vs 16%), febrile neutropenia (9% each), pyrexia (5% vs 7%), anemia (3% vs 9%), sepsis (0% vs 9%), autoimmune hemolytic anemia (0% vs 5%), and neutropenic sepsis (1% vs 5%), respectively. There were 8 (10%) on-treatment deaths in the OFA arm and 5 (12%) on-treatment deaths in the PC arm. Post-treatment anti-cancer therapies are described in Table 1. Conclusions: At the 5-year follow-up of this phase III trial, there was a numerical but statistically not significant longer median OS (+4.7 months) in the OFA arm. As only few patients had the chance to receive a kinase inhibitor later, the study displays the survival of BFR CLL patients in the period prior to receiving small molecule inhibitors. This and other studies have demonstrated a longer PFS with the use of low-dose maintenance CD20 monoclonal antibody therapy vs not, a finding that may be re-explored in the new targeted therapeutic landscape in CLL. OFA is a safe option in multi-resistant advanced CLL cases. Disclosures Miklos: AOP Orphan: Honoraria; Novo nordisk: Honoraria. Strugov:Janssen: Honoraria, Other: Travel expense, Research Funding; Abbvie: Other: Travel expense. Lewerin:Abbvie: Consultancy. Grosicki:Affimed: Research Funding. Steurer:Novartis: Consultancy, Honoraria, Research Funding. Montillo:Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Research Funding. Middeke:Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Stefanelli:Novartis: Employment, Equity Ownership. Vincent:Novartis: Employment. G:Novartis: Employment. Österborg:Beigene: Research Funding; Abbvie: Research Funding; Gilead: Consultancy, Research Funding; Janssen: Research Funding; Pharmacyclics: Research Funding.
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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