Lori Ann Leslie, MD
Combination regimens with low toxicity profiles are being explored in follicular lymphoma, as novel agents seem to have low single-agent activity in early lines of treatment, says Lori Ann Leslie, MD.
“The issue with monotherapies, such as ibrutinib (Imbruvica) and venetoclax (Venclexta), is that their activity as single agents is low. Finding combinations with tolerable toxicity profiles remains to be the main challenge,” said Leslie.
Moreover, data presented at the 2017 ASH Annual Meeting revealed studies that have confirmed the benefit of rituximab (Rituxan) in the maintenance setting of follicular lymphoma. Long-term follow-up of the PRIMA trial, for example, showed the benefit of maintenance rituximab versus observation post-upfront chemoimmunotherapy with R-CHOP.
However, in the phase III RELEVANCE study, the combination of rituximab and lenalidomide (Revlimid) followed by maintenance therapy with the same regimen did not improve response or progression-free survival (PFS) versus rituximab and chemotherapy with rituximab maintenance for patients with previously untreated follicular lymphoma.
In an interview during the 2018 OncLive®
State of the Science SummitTM
on Hematologic Malignancies, Leslie, lymphoma attending, John Theurer Cancer Center, provided expert insight on the latest developments in the field of follicular lymphoma.
OncLive: What is the state of the treatment paradigm in follicular lymphoma?
: A 10-year update from the PRIMA study, presented at the 2017 ASH Annual Meeting regarding the role of maintenance rituximab post-chemoimmunotherapy, showed a continued PFS benefit at 10 years. Over half of the patients who received maintenance rituximab versus observation did not require subsequent therapy compared with 35% in the observation arm. There is the use of maintenance rituximab following bendamustine/rituximab (BR) induction therapy. Though there are no clinical trials that are randomized to support this approach, there were some retrospective studies and analyses of prior follicular lymphoma cohorts that suggest a similar PFS benefit.
There are novel approaches in the upfront setting, but nothing is practice changing. In terms of prognostic models, there were some abstracts looking at the importance of including factors from the tumor microenvironment and host immune system, in addition to our more standard clinical and genetic risk factors used of the tumor itself.
Can you elaborate on the data presented in the maintenance setting?
The 10-year follow up of PRIMA, the randomized study looking at 2 years of maintenance rituximab versus observation after upfront chemoimmunotherapy, reported a greater than 50% PFS in the maintenance arm versus 35% in the observation arm. Though there was no difference in overall survival (OS), the use of maintenance rituximab made a significant difference in time to next treatment.
The BIONIC study looked at the use of bortezomib (Velcade) [added to BR] in the induction setting with or without the addition of lenalidomide [as continuation treatment] in the maintenance setting. This showed no increase in efficacy. Increased toxicity was seen with the addition of these agents, so it's not an approach that is being further pursued.
The last study that we discussed in the maintenance realm was the MAINTAIN study, which looked at the difference between 2 and 4 years of maintenance rituximab following BR induction therapy. This showed that there was no difference in PFS, but also no difference in toxicity between the 2 approaches. They then did a cross-trial analysis looking at 2 years of maintenance in the MAINTAIN study versus observation after BR. This was compared with a 2003 study in Hodgkin lymphoma, where 2-year maintenance treatment showed a similar PFS benefit versus observation without the OS benefit we had seen in other studies.
Is chemotherapy vital in the management of the disease?
As it stands now, yes. Induction includes chemotherapy for patients with follicular lymphoma. The RELEVANCE trial looked at the use of lenalidomide plus rituximab versus any chemoimmunotherapy in the upfront setting. We are eagerly awaiting those results; they will likely be reported at an upcoming meeting.
Have the results of the GALLIUM study impacted patients with follicular lymphoma?
The GALLIUM study was presented in 2016 and was recently published in the New England Journal of Medicine.
The study is looking at the upfront use of obinutuzumab (Gazyva), a type II anti-CD20 monoclonal antibody, versus rituximab in combination with chemotherapy followed by CD20-antibody maintenance therapy. The study showed a PFS benefit, but also an increased incidence of serious adverse events in the obinutuzumab group.