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Lenalidomide plus rituximab elicits favorable response in follicular lymphoma
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CHICAGO — The combination of lenalidomide and rituximab followed by maintenance resulted in favorable activity and tolerability in patients with follicular lymphoma considered double refractory or early relapsers, according to a phase 3b randomized study presented at the ASCO Annual Meeting.
“The prognosis for follicular lymphoma continues to improve over time as we continue to introduce more novel therapies into our armamentarium,” David. J. Andorsky, MD, medical oncologist at Rocky Mountain Cancer Centers, said during his presentation.
Median OS for follicular lymphoma is around 15 years, Andorsky added.
“However, there are subsets of patients who have worse outcomes,” he said. “In particular, patients who relapse within 2 years of their initial diagnosis only have a 50% 5-year OS, compared with 90% for patients who do not relapse within 2 years. That is one population of early relapsers that most needs new novel therapies. In addition, patients who were refractory to rituximab have worse outcomes and few treatment options.”
The multicenter, open-label MAGNIFY trial included patients with relapsed or refractory non-Hodgkin lymphoma, including grade 1 to grade 3b or transformed follicular lymphoma.
The analysis focuses on 117 patients with relapsed or refractory follicular lymphoma. Researchers considered 27% of patients (median age, 64 years) double refractory — or refractory to rituximab (Rituxan; Genentech, Biogen) as monotherapy or in a combination and an alkylating agent — and considered 37% of patients (median age, 65 years) early relapsers because they had progressed or relapsed within 2 years of initial diagnosis.
Patients had a median of two prior regimens of chemotherapy. Of the early relapsers, 31 had first-line rituximab-based chemotherapy and 12 had rituximab monotherapy or another treatment.
A majority of the double-refractory (94%) and early relapse (91%) cohorts had grade 1 to grade 3a follicular lymphoma, whereas only one patient from each group had transformed follicular lymphoma. Seventy-two percent of double-refractory patients and 49% of early relapsers had stage IV disease at study entry.
Following 12 cycles of lenalidomide (Revlimid, Celgene) plus rituximab, researchers randomly assigned patients with stable disease 1:1 to maintenance lenalidomide plus rituximab or rituximab alone.
PFS served as the primary endpoint.
Researchers reported overall response rates of 67% in all patients, 46% in double-refractory patients and 48% in early relapsers. Rates of complete response included 36% for all patients, 21% for double-refractory patients and 12% for early relapsers.
Stable disease occurred in 36% of double-refractory patients, 29% of early relapsers, and 23% of the total follicular lymphoma population. Progressive disease occurred in 18% of double-refractory patients, 12% of early relapsers and 10% of all patients.
Researchers reported median time to response of 2.8 months for double-refractory patients and 2.7 months for early relapse patients, with median duration of response not reached.
Sixty-six percent of patients achieved 1-year PFS, which represented 66% of double refractory patients and 45% of early relapse patients. Rate of 1-year PFS appeared higher in early relapse patients treated with first-line rituximab vs. other treatments (50% vs. 27%).
Common grade 3 or worse adverse events for all patients included neutropenia (53% double refractory; 33% early relapse), leukopenia (9%; 12%), and lymphopenia (9%; 5%).
“The combination of lenalidomide and rituximab is a well-tolerated therapy that holds great promise in this difficult-to-treat subset of populations with follicular lymphomas,” Andorsky said. – by Chuck Gormley
References:
Andorsky DJ, et al. Abstract 7502. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.
Disclosure: Researchers report no relevant financial disclosures.
Perspective
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Andre Goy, MD, MS
The response is very consistent in patients with follicular lymphoma who are double refractory or have early relapse, which addresses an unmet need. Follicular lymphoma is a disease that can be treated over and over with multiple therapies, because patients can relapse over time. Typically, we do not have good ways to identify ahead of time patients who relapse within 2 years of induction therapy or who are double refractory, and once we see them they are most challenging to treat. Younger patients tend to go onto autologous transplant or a CAR T-cell program.
This study does not have very long follow-up, but having patients with overall response rates of close to 50% for double-refractory and early relapse cohorts with a significant proportion of complete response is impressive. However, we need more follow-up because we only have a 1-year PFS of 66%, although in this population, 66% is interesting. This is not a heavily pretreated population so, overall, these are favorable results.
The toxicity profile also is favorable because these patients would not respond well to rituximab (Rituxan; Genentech, Biogen) alone. This is a modality of immunotherapy that is being looked at across the board in relapse settings in a number of trials in follicular lymphoma. It is impressive to see that just by adding lenalidomide (Revelimid, Celgene) to rituximab we can have a durable response. When we have no other options, we can use these agents in patients with follicular lymphoma and expect them to be relatively well tolerated. Hopefully, we can shy away from chemotherapy in many patients and build upon immunotherapy advances.
Perspective
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Brad S. Kahl, MD
In the MAGNIFY trial we learned that the lenalidomide (Revlimid, Celgene) and rituximab (Rituxan; Genentech, Biogen) regimen is very promising in a group of patients with high-risk, refractory follicular lymphoma, with an overall response rate of over 60% and a 1-year PFS rate of nearly 70%. The regimen looks very promising in the frontline, with ORR of 98% and a 3-year PFS close to 88%.
This led to the design of the RELEVANCE trial, in which researchers randomly assigned 1,000 patients to either chemotherapy or rituximab plus lenalidomide. This will be an important study, and we anxiously await the results so we can consider it a standard of care.
It does seem to me that, in terms of biologic risk stratification, follicular lymphoma is starting to lag behind other lymphomas substantially. We lack prognostic biomarkers like we have in chronic lymphocytic lymphoma, and some of these prognostic biomarkers can be used for predictive purposes in follicular lymphoma. At the moment, our best risk-stratification tool is the length of first remission, which leaves us with the challenge of determining how to identify these patients at diagnosis.
This study is clearly a step in the right direction. Looking forward, the challenge is on us to develop better risk stratification for follicular lymphomas.
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