DYNAMO: A PHASE 2 STUDY DEMONSTRATING THE CLINICAL ACTIVITY OF DUVELISIB IN PATIENTS WITH DOUBLE-REFRACTORY FOLLICULAR LYMPHOMA
Author(s): ,
Pier Luigi Zinzani
Affiliations:
1. Institute of Hematology Serágnoli,University of Bologna,Bologna,Italy
,
Nina Wagner-Johnston
Affiliations:
Siteman Cancer Center,Washington University,St Louis,United States
,
Carole Miller
Affiliations:
Saint Agnes Hospital,Baltimore,United States
,
Kirit Ardeshna
Affiliations:
University College London,London,United Kingdom
,
Scott Tertreault
Affiliations:
Florida Cancer Specialists Tallahassee,Tallahassee,United States
,
Sarit Assouline
Affiliations:
Jewish General Hospital,Montreal,Canada
,
Francesco Passamonti
Affiliations:
Ospedale Di Circolo e Fondazione Macchi U.O. Ematologia,Varese,Italy
,
Scott Lunin
Affiliations:
Florida Cancer Specialist - Fort Myers,Fort Myers,United States
,
Andrew Pettitt
Affiliations:
University of Liverpool,Liverpool,United Kingdom
,
Zsolt Nagy
Affiliations:
Semmelweis Egyetem, I. sz. Belgyogyaszati Klinika,Budapest,Hungary
,
Oliver Tournilhac
Affiliations:
CHU Estaing - Service d'hématologie,Clermont-Ferrand,France
,
Karim Nassar
Affiliations:
Centre intégré de santé et de services sociaux de l'Outaouais,Quebec,Canada
Ian Flinn
Affiliations:
Tennessee Oncology,Nashville,United States
(Abstract release date: May 18, 2017) EHA Learning Center. Luigi Zinzani P. Jun 25, 2017; 182064
Pier Luigi Zinzani
Pier Luigi Zinzani

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Abstract
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Abstract: S777

Type: Oral Presentation

Presentation during EHA22: On Sunday, June 25, 2017 from 08:45 - 09:00

Location: Hall C

Background
Duvelisib is an oral, dual inhibitor of PI3K-δ,γ in development for the treatment of hematologic malignancies. DYNAMO is a Phase 2 study to evaluate the safety and efficacy of duvelisib monotherapy in a double refractory iNHL population, which included a majority of patients (pts) with follicular lymphoma (FL).

Aims
The primary objective was to evaluate the antitumor activity of duvelisib monotherapy in pts whose disease is refractory to rituximab and to either chemotherapy or RIT, with an additional objective to further characterize the safety of duvelisib.

Methods
DYNAMO is an open-label, single-arm, safety, and efficacy study in patients (pts) with FL, small lymphocytic lymphoma (SLL), or marginal zone lymphoma (MZL), whose disease is double-refractory to rituximab (monotherapy or in combination) and to chemotherapy or radioimmunotherapy. Pts received duvelisib 25 mg BID in 28-day treatment cycles until disease progression or unacceptable toxicity. The primary endpoint is overall response rate (ORR) as assessed by an independent review committee (IRC) per revised IWG criteria. Secondary endpoints include duration of response (DoR), progression-free survival (PFS), overall survival (OS), time to response (TTR), adverse events (AEs) and other safety parameters. Pneumocystis jiroveci pneumonia (PJP) prophylaxis was mandated for all pts.

Results
129 pts with iNHL were treated on study. Of these, 83 pts with FL received duvelisib with a median duration of exposure of 6 mo. (range: 0.4 - 24). Median age was 64 years; 68% were male. Most FL pts had an ECOG performance status score at baseline of 0 (51%), followed by 1 (42%) and 2 (7%). Most FL pts (65%) had a FLIPI score at baseline ≥ 3, and most had either Stage 3 (46%) or Stage 4 (39%) disease. Median time from last anticancer therapy to first dose of duvelisib was 3.2 months. FL pts received a median of 3 prior anticancer regimens (range: 1 - 10); 65% of pts received ≥ 3 prior regimens, 17% ≥ 6 prior regimens.

The ORR was 41% (CI: 30, 52), all of which were PRs. 36% of pts had SD as best response, and 17% had PD as best response. 6% of pts were not evaluable, as they only had a baseline scan. Median TTR was 1.9 mo. (range: 1.6 - 11.7). 80% of FL pts experienced a reduction in nodal target lesions after treatment with duvelisib. Among the 34 FL pts with a response per IRC, the median DoR was 9.2 months. The median PFS for all FL pts was 8.3 months, while the median OS was 11.1 months.
Among all pts treated on study (n=129), AEs were mostly Gr 1-2. Most common ≥ Gr 3 AEs were transient cytopenias [neutropenia (23%), anemia (12%), and thrombocytopenia (10%)] and diarrhoea (15%). 17% of pts discontinued duvelisib due to an AE. Opportunistic infections occurred in < 5% of pts, none were fatal, and included 1 pt (0.8%) with pneumocystis and 3 pts (2.3%) with CMV infections. Six pts had an AE with a fatal outcome. 

Conclusion
In DYNAMO, duvelisib showed clinical activity in a double-refractory FL population (41% ORR, median DoR 9.2 mo., 80% with reduction in target lesions). Duvelisib was generally well tolerated, with a manageable safety profile with appropriate risk mitigation. Duvelisib monotherapy has a favorable benefit-risk profile in double-refractory iNHL, and may represent an important treatment option. Updated clinical data will be available at the time of presentation.  

Session topic: 19. Indolent Non-Hodgkin lymphoma - Clinical

Keyword(s): PI3K, Phase II, Follicular lymphoma, Clinical data

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