R-HyperCVAD
R-HyperCVAD is another option in younger patients, and is usually given for eight cycles, followed by transplant only in those who aren’t in complete remission, Dr. Blum said.
Median failure-free survival among patients aged 65 years and younger in one study of this regimen was 6.5 years and OS was 13.4 years. In those over age 65, median failure-free survival was about 3 years (Br J Haematol. 2016 Jan;172[1]:80-88).
The SWOG 0213 study looked at this in a multicenter fashion, she said, noting that 39% of patients – 48% of whom were aged 65 and older – could not complete all eight cycles.
“Again, there was a high rate of this sort of infectious toxicity,” she said.
Median PFS was about 5 years in this study as well, and OS was nearly 7 years. For those over age 65, median PFS was just 1.6 years.
“So I don’t typically recommend this for the 65- to 70-year-olds,” she said.
Older nontransplant candidates
When treating patients who are unfit for transplant, Dr. Blum pointed to the results of the StiL and BRIGHT studies, which both showed that R-bendamustine was noninferior to R-CHOP as first-line treatment.
In addition, recent data on combined bendamustine and cytarabine (R-BAC500) showed that in 57 patients with a median age of 71 years, 95% received at least four cycles, and 67% completed six cycles. CR was 91% , and 2-year OS and PFS were 86% and 81%, respectively.
However, grade 3-4 neutropenia and thrombocytopenia occurred in 49% and 52% of patients, respectively (Lancet Haematol. 2017 Jan 1;4[1]:e15-e23).
The bortezomib-containing regimen VR-CAP has also been shown to be of benefit for older MCL patients not eligible for transplant, she said.
Median PFS with VR-CAP in a study of 487 newly diagnosed MCL patients was about 25 months vs. 14 months with R-CHOP (N Engl J Med. 2015 Mar 5;372:944-53).
“R-lenalidomide has activity in the front-line setting as well,” Dr. Blum said, citing a multicenter phase 2 study of 38 patients with a mean age of 65 years. The intention-to-treat analysis showed an overall response rate of 87%, CR rate of 61%, and 2-year PFS of 85% (N Engl J Med. 2015;373:1835-44).
Maintenance therapy
As for maintenance therapy in younger patients, a phase 3 study of 299 patients showed that rituximab maintenance was associated with significantly better 4-year PFS (83% vs. 64% with observation), and 4-year OS (89% vs. 80% with observation), she said (N Engl J Med. 2017 Sep 28;377:1250-60).
“I do think that rituximab maintenance is the standard of care now, based on this study,” Dr. Blum said, adding that there is also a role for rituximab maintenance in older patients.
A European Mantle Cell Network study of patients aged 60 and older (median age of 70) showed an OS of 62% with R-CHOP vs. 47% with R-FC (rituximab, fludarabine, and cyclophosphamide), and – among those then randomized to maintenance rituximab or interferon alpha – 4-year PFS of 58% vs. 29%, respectively (N Engl J Med. 2012;367:520-31).
“Now I will tell you that most of these patients are getting bendamustine. We don’t really know the role for rituximab maintenance after bendamustine-based induction, but at this point I think it’s reasonable to consider adding it,” she said.
Dr. Blum is a consultant for Acerta, AstraZeneca, and Molecular Templates and has received research funding from Acerta, AstraZeneca, Celgene, Cephalon, Immunomedics, Janssen, Merck, Millennium, Molecular Templates, Novartis, Pharmacyclics, and Seattle Genetics.