Washington, DC—A chemotherapy–immunotherapy combination has been shown to be extremely effective in a small clinical trial of previously untreated mantle-cell lymphoma, leading to objective responses in every patient, including complete responses in almost 90%, investigators reported at the 2013 American Association for Cancer Research annual meeting.
All 37 patients had at least partial responses to treatment with the combination of vorinostat (Zolinza), cladribine (Leustatin), and rituximab (Rituxan). The regimen achieved complete responses in 32 (86%) patients and in 29 of 32 (91%) patients who have completed the planned 6 cycles of therapy.
With follow-up for as long as 34 months (median, 13 months), the median progression-free survival has yet to be reached, reported Kamal Sharma, DO, a hematologist at Penn State Milton S. Hershey Medical Center, State College, PA.
“This is a safe and effective combination in previously untreated mantle-cell lymphoma,” said Dr Sharma. “Myelosuppression is the primary toxicity and is reversible.”
Mantle-cell lymphoma has no generally accepted standard regimen, although the combination of rituximab and cladribine has been cited in the National Comprehensive Cancer Network’s Clinical Practice Guidelines® for achieving durable responses in a substantial proportion of patients.
In an effort to build on the success of that immunologic–epigenetic combination, Dr Sharma and colleagues have added the histone deacetylase inhibitor vorinostat to the mix.
The regimen is administered in 28-day cycles that continue until completion of at least 6 cycles, disease progression, or development of unacceptable toxicity. Of the first 40 patients enrolled in this study, 32 completed 6 cycles of therapy, and treatment is ongoing for 3 others. None of the patients underwent stem-cell transplantation, nor was an attempt made to harvest stem cells, said Dr Sharma.
Hematologic toxicity consisted of neutropenia (all grades) in 32% of patients (including 11% with grade 3 or 4) and thrombocytopenia in 20% (5% with grade 3 or 4). Fatigue has been the most frequent nonhematologic toxicity.
These “remarkable results” require validation, including laboratory studies to determine the underlying mechanisms for the regimen’s activity, which has been dramatic in some patients, commented Kenneth C. Anderson, MD, Chief of the Division of Hematologic Neoplasia, Dana-Farber Cancer Institute, Boston.