Mantle Cell Lymphoma -- Still More Questions Than Answers
Mantle Cell Lymphoma -- Still More Questions Than Answers
Among the novel drugs recently approved for patients with relapsed MCL, bortezomib has also shown activity as first-line therapy in recent phase 2 trials of combination regimens, such as VcR-CVAD (bortezomib combining rituximab, cyclophosphamide, doxorubicin, vincristine, and dexamethasone) and RiPAD+C (rituximab, bortezomib, doxorubicin, dexamethasone, and chlorambucil). However, Dr. Vose commented, "bortezomib has some side effects, mostly neuropathy, that are not tolerable in older patients."
"Ibrutinib is probably the most likely to be used next," she predicted. The orally active Bruton tyrosine kinase (BTK) inhibitor was approved in the United States in November 2013, on the basis of phase 2 study results, and it is included in the latest National Comprehensive Cancer Network guidelines as a recommended second-line therapy. "Ibrutinib is quite easily tolerated and could be used in older patients," she said. Clinical trials with ibrutinib in combination as first-line therapy are ongoing in MCL, including a phase 3 study of ibrutinib in combination with bendamustine and rituximab and a phase 1b trial assessing the feasibility of incorporating ibrutinib into R-CHOP. Whether ibrutinib will be effective in only a limited proportion of MCL patients and that resistance to the drug may develop in a number of patients, as recently suggested, "is not yet known," Dr. Vose said.
Among the other novel agents being investigated as components of combination therapy or as maintenance or consolidation treatment, "idelalisib, an oral PI3K delta inhibitor, is interesting and has good activity in MCL," Dr. Vose noted. "A recently published phase 1 study showed idelalisib to be active and well tolerated in heavily pretreated patients with MCL. In contrast, histone deacetylase inhibitors -- such as vorinostat, which is approved by the US Food and Drug Administration for use in cutaneous T cell lymphoma and has been reported as promising in MCL in phase 1/2 studies -- have minimal activity and are not really impressive," according to Dr. Vose.
Despite accumulating evidence, the best therapeutic strategy remains elusive. "No one really knows whether you should do a transplant in first remission, the maintenance question is unresolved, and nobody knows the right regimen for relapse," said Dr. Vose, concluding that the best therapeutic strategy in MCL remains an open question.
The Line-up of New Agents
Among the novel drugs recently approved for patients with relapsed MCL, bortezomib has also shown activity as first-line therapy in recent phase 2 trials of combination regimens, such as VcR-CVAD (bortezomib combining rituximab, cyclophosphamide, doxorubicin, vincristine, and dexamethasone) and RiPAD+C (rituximab, bortezomib, doxorubicin, dexamethasone, and chlorambucil). However, Dr. Vose commented, "bortezomib has some side effects, mostly neuropathy, that are not tolerable in older patients."
"Ibrutinib is probably the most likely to be used next," she predicted. The orally active Bruton tyrosine kinase (BTK) inhibitor was approved in the United States in November 2013, on the basis of phase 2 study results, and it is included in the latest National Comprehensive Cancer Network guidelines as a recommended second-line therapy. "Ibrutinib is quite easily tolerated and could be used in older patients," she said. Clinical trials with ibrutinib in combination as first-line therapy are ongoing in MCL, including a phase 3 study of ibrutinib in combination with bendamustine and rituximab and a phase 1b trial assessing the feasibility of incorporating ibrutinib into R-CHOP. Whether ibrutinib will be effective in only a limited proportion of MCL patients and that resistance to the drug may develop in a number of patients, as recently suggested, "is not yet known," Dr. Vose said.
Among the other novel agents being investigated as components of combination therapy or as maintenance or consolidation treatment, "idelalisib, an oral PI3K delta inhibitor, is interesting and has good activity in MCL," Dr. Vose noted. "A recently published phase 1 study showed idelalisib to be active and well tolerated in heavily pretreated patients with MCL. In contrast, histone deacetylase inhibitors -- such as vorinostat, which is approved by the US Food and Drug Administration for use in cutaneous T cell lymphoma and has been reported as promising in MCL in phase 1/2 studies -- have minimal activity and are not really impressive," according to Dr. Vose.
Despite accumulating evidence, the best therapeutic strategy remains elusive. "No one really knows whether you should do a transplant in first remission, the maintenance question is unresolved, and nobody knows the right regimen for relapse," said Dr. Vose, concluding that the best therapeutic strategy in MCL remains an open question.
