EHA 2017: The DYNAMO Study: Duvelisib in Double-Refractory Follicular Lymphoma and Small Lymphocytic Lymphoma
Long-term follow-up data from the DYNAMO study, which met its primary endpoint of overall response rate (ORR; P = .0001) at the final analysis, was presented at the 22nd Congress of the European Hematology Association (EHA) (Abstracts S777, E1130).
DYNAMO is a phase II clinical study evaluating duvelisib, an investigational dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, in patients with indolent non-Hodgkin lymphoma (NHL) whose disease is refractory to both rituximab (Rituxan) and chemotherapy or radioimmunotherapy. The presentations focus on the subsets of patients with follicular lymphoma or small lymphocytic lymphoma who were enrolled in DYNAMO.
Oral Duvelisib in Patients With Double-Refractory Follicular Lymphoma
With 18 months of follow-up, the data continues to be consistent with the primary analysis.
Of the 83 patients with double-refractory follicular lymphoma enrolled in DYNAMO (median 3 prior anticancer regimens [range 1–10]), 36 responded, which included 1 (1%) complete response (CR) and 35 (42%) partial responses (PR), for an ORR of 43% as determined by an independent review committee. Responses generally occurred shortly after the start of treatment (median 2 months). Notably, 83% of evaluable patients with follicular lymphoma treated with duvelisib had a reduction in the size of their target lymph nodes. Median duration of response was 7.9 months, median progression-free survival was 8.3 months, and median overall survival was 27.8 months.
The safety profile of duvelisib monotherapy remains consistent with what has been previously reported in indolent NHL and other advanced hematologic malignancies. In these double-refractory follicular lymphoma patients, the most common grade ≥ 3 hematologic adverse events were neutropenia (22%), anemia (13%), and thrombocytopenia (9%). Diarrhea was the most frequently reported nonhematologic adverse event (47%; 16% grade ≥ 3). As expected in a heavily pretreated and refractory patient population, severe infections were observed (20%). Pneumonitis and colitis remained relatively uncommon (each 5%). Treatment discontinuations attributed to severe adverse events were infrequent, suggesting that these events were generally manageable.
Oral Duvelisib in Patients With Double-Refractory Small Lymphocytic Lymphoma
Of the 28 patients with double-refractory small lymphocytic lymphoma enrolled in DYNAMO (median 3 prior anticancer regimens [range 1–18]), 19 responded, all of which were PRs, for an ORR of 68% as determined by an independent review committee. Responses generally occurred shortly after the start of treatment (median 2 months). Importantly, 100% of evaluable patients with double-refractory small lymphocytic lymphoma treated with duvelisib had a reduction in the size of their target lymph nodes. With a median time on duvelisib of 12 months, median duration of response was 10.1 months, median progression-free survival was 11.7 months, and median overall survival was 28.9 months.
In these double-refractory small lymphocytic lymphoma patients, the most common grade ≥ 3 hematologic adverse events were neutropenia (32%), thrombocytopenia (21%), and anemia (21%). The most frequently reported grade ≥ 3 nonhematologic adverse events were pneumonia (14%), increases in alanine aminotransferase (7%) and aspartate aminotransferase (11%), and diarrhea (11%). As expected in a heavily pretreated and refractory patient population, severe infections were observed (36%). Colitis occurred in 3 (11%) small lymphocytic lymphoma patients. No double-refractory small lymphocytic lymphoma patients experienced pneumonitis. Treatment discontinuations attributed to the most common adverse events were infrequent, suggesting that these events were generally manageable.
Commentary
“We believe that oral duvelisib has the potential to be an important new treatment option for lymphoma patients,” commented Pier Luigi Zinzani, MD, PhD, of the University of Bologna Institute of Hematology, an investigator participating in the study. “What I find particularly encouraging are the responses we saw in patients with double-refractory disease, a population with few treatment options left. The data we are presenting at EHA continue to demonstrate that duvelisib monotherapy can achieve meaningful and durable responses.”
Hagop Youssoufian, MSc, MD, Head of Hematology and Oncology Development at Verastem, stated, “The data from DYNAMO remain positive, and reporting the results from long-term follow-up is important for the medical community and for the overall development of duvelisib. Oral duvelisib monotherapy has demonstrated clinical activity across a number of hematologic cancers, including chronic lymphocytic leukemia, indolent NHL, and T-cell lymphoma. Based on the results we have seen thus far, we remain fully committed to exploring duvelisib’s potential across a wide range of lymphoid malignancies.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
