On Sunday December 10th 2017, during an oral abstract session at the 59th Annual meeting of the American Society of Hematology (ASH), Ian Flinn of the Sarah Cannon Research Institute in Nashville, TN on behalf of his colleagues, presented results from the phase III DUO trial (NCT02004522). It was an international, multi-center randomized study comparing duvelisib (DUV) to ofatumumab (OFA) in relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
This abstract (#432), “Results from the Phase 3 DUO Trial: A Randomized Comparison of Duvelisib Vs Ofatumumab in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma,” was presented during Oral Session: 642. “CLL: Therapy, excluding Transplantation: Targeting MRD Negative CLL with Combinations of Novel Agents and Chemoimmunotherapy Regimens, New Treatments.” In the summary below, data from the live session at ASH is used and therefore may supersede information in the pre-published Abstract.
- Duvelisib (DUV) monotherapy demonstrated a significant improvement in progression-free survival compared to ofatumumab in CLL/SLL patients (13.9 months vs. 9.9 months; HR=0.52, P < 0.0001)
- 319 patients were randomized 1:1 to either oral DUV 25 mg twice daily administered until disease progression (n = 160), or IV OFA 300 mg x1 then 2000 mg for 12 doses total, per label (n = 159)
- Response assessment occurred on day 1 of cycle 3 (C3), C5, C7, C11, C15, C19, and every 6 months thereafter
- Primary endpoint was progression-free survival (PFS) as assessed by a blinded independent review committee (IRC)
- Secondary endpoints included overall response rate (ORR), overall survival (OS), and safety
- Median PFS (IRC): DUV, 13.3 months; OFA, 9.9 months (P < 0.0001, HR=0.52)
- Significantly longer PFS with DUV (12.7 months) vs. OFA (9.0 months) in patients with 17p deletion (P < 0.0011, HR=0.41)
- ORR: DUV, 73.8%; OFA, 45.3% (P < 0.0001)
- DUV (85%) significantly reduced lymph node burden >50% in most patients compared to OFA (16%)
- Adverse events of special interest but rarely led to discontinuation were rash, pneumonitis, transaminitis, colitis, pneumonia, diarrhea, and neutropenia
- With a median exposure of 50 weeks, “the AE profile of duvelisib was manageable and consistent with what has been previously observed.”
In this large phase III clinical trial in relapsed/refractory CLL/SLL, duvelisib clearly and demonstrably showed significantly longer PFS when compared to ofatumumab. With a relatively manageable group of adverse events and toxicities, DUV will quickly and deservedly serve as a new treatment option for these patients. The DUO trial has proven that there is yet another formidable therapy for CLL/SLL patients on the horizon.
Associate Professor Nicole Lamanna discusses the outcomes of the DUO trial in an interview with Lymphoma Hub at ASH 2017, watch here.