Choice of First-Line Therapy in Follicular Lymphoma Debated
Choice of First-Line Therapy in Follicular Lymphoma Debated
After years of debate over when to start treatment for follicular non-Hodgkin's lymphoma and when to "watch and wait," most experts now agree that patients with advanced disease who are symptomatic should be treated.
However, what therapy to use in the first instance remains "a conundrum," write Oliver Press, MD, PhD, from the Fred Hutchinson Cancer Research Center, and Maria Corinna Palanca-Wessels, MD, PhD, from the University of Washington, both in Seattle, in an editorial published in the April 20 issue of the Journal of Clinical Oncology.
They say there is no question now that rituximab (MabThera, Roche/Genentech) should be used, but what should it be used with?
The editorial was prompted by the publication of results from a large Italian phase 3 trial, known as FOLL05, which compared 3 chemotherapy regimens: R-CHOP (rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone); R-CVP (rituximab with cyclophosphamide, vincristine, and prednisolone); and R-FM (rituximab with fludarabine and mitoxantrone).
FOLL05, conducted by the Fondazione Italiana Linformi, began in 2006 and involved 534 patients. The median follow-up of 34 months "supports R-CHOP as the reference regimen for initial management of patients with follicular lymphoma requiring active treatment," conclude Massimo Federico, MD, from the University of Modena, and colleagues.
On the basis of their results and those from another large phase 3 trial, the Primary Rituximab and Maintenance (PRIMA) trial, they suggest that this induction therapy be followed by 2 years of maintenance rituximab therapy.
The PRIMA trial also compared 3 regimens — R-CHOP, R-CVP, and R-FCM (rituximab plus fludarabine, cyclophosphamide, and mitoxantrone). It involved 1202 patients, and although the treatment allocation was not randomized, but left to "physician choice," the "conclusions are identical to those reported in the FOLL05 trial," the editorialists note.
These conclusions — that initial therapy should be with R-CHOP and that this should be followed by 2 years of rituximab maintenance in patients who respond — "are reasonable," say the editorialists.
However, they point out that "alternative perspectives are also supportable."
In fact, the FOLL05 authors make this point, too. "New questions have already arisen regarding both the efficacy of new promising drugs and best patient management at the end of induction therapy," Dr. Federico and colleagues write.
Simpler 2-Drug Regimen
One promising approach is the use of bendamustine plus rituximab (BR). Two large trials comparing BR with R-CHOP have suggested similar efficacy but less toxicity with the simpler 2-drug combination. When these results were presented last year at the annual meeting of the American Society of Clinical Oncology, they were hailed as practice-changing. They have since caused a huge stir among lymphoma experts.
Even though the results of the comparison between BR and R-CHOP have not yet been published, they have been "enormously influential," write Drs. Press and Palanca-Wessels in their editorial.
Recent surveys have suggested that BR has already supplanted R-CHOP as the most popular and widely used regimen in both North America and Western Europe, they note, with an estimated 50% to 70% of patients with follicular lymphoma receiving it as first-line therapy.
However, so far, no difference in overall survival between BR and R-CHOP has been reported, so the relative merits of these 2 regimens "are certain to remain contentious for the foreseeable future," the editorialists note.
Another alternative is radioimmunotherapy for consolidation after first remission induced by chemotherapy, they note.
Two different radioimmunotherapeutics are available for this use — yttrium ibritumomab tiuxetan (Zevalin) and 131-iodine-tositumomab (Bexxar), which has also been investigated as a stand-alone initial treatment.
These radioimmunotherapeutics are very effective; in fact, this is "probably the most effective, yet least used, treatment for follicular lymphoma," according to Bruce Cheson, MD, from the Lombardi Comprehensive Cancer Center at Georgetown University Hospital in Washington, DC. Amid all the excitement about new drugs and drug combinations, radioimmunotherapy "has been sort of forgotten in the process," he said in his MedscapeCheson on Oncology videoblog.
One of the problems is that radioimmunotherapy is not readily available. Usually, an oncologist will have to refer patients to a facility with nuclear medicine capabilities, and "you need to really coordinate among the people who are providing the therapy," Dr. Cheson noted. It is also expensive, and there have been problems with reimbursement. However, the treatment itself is easy and quick (lasting only 8 days), and it is a good therapy for appropriate patients.
Dr. Federico has disclosed no relevant financial relationships. Coauthor Umberto Vitolo, MD, from Azienda Ospedaliera Universitaria "San Giovanni Battista," in Torino, Italy, reports serving as a consultant for Roche. Dr. Press reports serving as a consultant to Roche/Genentech. Dr. Press and Dr. Palanca-Wessels report receiving research funding from Roche/Genentech. Dr. Cheson reports serving as a director, officer, partner, employee, advisor, consultant, or trustee for Celegene, Cephalon, Allos, Gilead, Pharmacyclics, and Avila.
J Clin Oncol. 2013;31:1496-1498, 1506-1513. Editorial, Abstract
After years of debate over when to start treatment for follicular non-Hodgkin's lymphoma and when to "watch and wait," most experts now agree that patients with advanced disease who are symptomatic should be treated.
However, what therapy to use in the first instance remains "a conundrum," write Oliver Press, MD, PhD, from the Fred Hutchinson Cancer Research Center, and Maria Corinna Palanca-Wessels, MD, PhD, from the University of Washington, both in Seattle, in an editorial published in the April 20 issue of the Journal of Clinical Oncology.
They say there is no question now that rituximab (MabThera, Roche/Genentech) should be used, but what should it be used with?
The editorial was prompted by the publication of results from a large Italian phase 3 trial, known as FOLL05, which compared 3 chemotherapy regimens: R-CHOP (rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone); R-CVP (rituximab with cyclophosphamide, vincristine, and prednisolone); and R-FM (rituximab with fludarabine and mitoxantrone).
FOLL05, conducted by the Fondazione Italiana Linformi, began in 2006 and involved 534 patients. The median follow-up of 34 months "supports R-CHOP as the reference regimen for initial management of patients with follicular lymphoma requiring active treatment," conclude Massimo Federico, MD, from the University of Modena, and colleagues.
On the basis of their results and those from another large phase 3 trial, the Primary Rituximab and Maintenance (PRIMA) trial, they suggest that this induction therapy be followed by 2 years of maintenance rituximab therapy.
The PRIMA trial also compared 3 regimens — R-CHOP, R-CVP, and R-FCM (rituximab plus fludarabine, cyclophosphamide, and mitoxantrone). It involved 1202 patients, and although the treatment allocation was not randomized, but left to "physician choice," the "conclusions are identical to those reported in the FOLL05 trial," the editorialists note.
These conclusions — that initial therapy should be with R-CHOP and that this should be followed by 2 years of rituximab maintenance in patients who respond — "are reasonable," say the editorialists.
However, they point out that "alternative perspectives are also supportable."
In fact, the FOLL05 authors make this point, too. "New questions have already arisen regarding both the efficacy of new promising drugs and best patient management at the end of induction therapy," Dr. Federico and colleagues write.
Simpler 2-Drug Regimen
One promising approach is the use of bendamustine plus rituximab (BR). Two large trials comparing BR with R-CHOP have suggested similar efficacy but less toxicity with the simpler 2-drug combination. When these results were presented last year at the annual meeting of the American Society of Clinical Oncology, they were hailed as practice-changing. They have since caused a huge stir among lymphoma experts.
Even though the results of the comparison between BR and R-CHOP have not yet been published, they have been "enormously influential," write Drs. Press and Palanca-Wessels in their editorial.
Recent surveys have suggested that BR has already supplanted R-CHOP as the most popular and widely used regimen in both North America and Western Europe, they note, with an estimated 50% to 70% of patients with follicular lymphoma receiving it as first-line therapy.
However, so far, no difference in overall survival between BR and R-CHOP has been reported, so the relative merits of these 2 regimens "are certain to remain contentious for the foreseeable future," the editorialists note.
Another alternative is radioimmunotherapy for consolidation after first remission induced by chemotherapy, they note.
Two different radioimmunotherapeutics are available for this use — yttrium ibritumomab tiuxetan (Zevalin) and 131-iodine-tositumomab (Bexxar), which has also been investigated as a stand-alone initial treatment.
These radioimmunotherapeutics are very effective; in fact, this is "probably the most effective, yet least used, treatment for follicular lymphoma," according to Bruce Cheson, MD, from the Lombardi Comprehensive Cancer Center at Georgetown University Hospital in Washington, DC. Amid all the excitement about new drugs and drug combinations, radioimmunotherapy "has been sort of forgotten in the process," he said in his MedscapeCheson on Oncology videoblog.
One of the problems is that radioimmunotherapy is not readily available. Usually, an oncologist will have to refer patients to a facility with nuclear medicine capabilities, and "you need to really coordinate among the people who are providing the therapy," Dr. Cheson noted. It is also expensive, and there have been problems with reimbursement. However, the treatment itself is easy and quick (lasting only 8 days), and it is a good therapy for appropriate patients.
Dr. Federico has disclosed no relevant financial relationships. Coauthor Umberto Vitolo, MD, from Azienda Ospedaliera Universitaria "San Giovanni Battista," in Torino, Italy, reports serving as a consultant for Roche. Dr. Press reports serving as a consultant to Roche/Genentech. Dr. Press and Dr. Palanca-Wessels report receiving research funding from Roche/Genentech. Dr. Cheson reports serving as a director, officer, partner, employee, advisor, consultant, or trustee for Celegene, Cephalon, Allos, Gilead, Pharmacyclics, and Avila.
J Clin Oncol. 2013;31:1496-1498, 1506-1513. Editorial, Abstract
