Time to treatment response in patients with follicular lymphoma treated with bortezomib is longer compared with other histologic subtypes.
OBJECTIVE
To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma.


METHODS
Patients with follicular lymphoma (FL), marginal zone lymphoma, mantle cell lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, and Waldenstrom's macroglobulinemia were eligible for study. Bortezomib was given at a dose of 1.5 mg/m(2) as an i.v. push on days 1, 4, 8, and 11 of a 21-day cycle. Eligibility included the following: (a) no more than three prior therapies, (b) at least 1 month since prior chemotherapy, (c) measurable disease, and (d) an absolute neutrophil count of >1,000/microL and a platelet count >50,000/microL for the first dose of any cycle.


RESULTS
Seventy-seven patients were registered, of which 69 were assessable for response based on the completion of two cycles of therapy. Subtypes included FL (59.5%), mantle cell lymphoma (52%), small lymphocytic lymphoma/chronic lymphocytic leukemia (16.2%), marginal zone lymphoma (21.6%), and one Waldenstrom's macroglobulinemia. The median number of prior therapies was three. The most common grade 3 toxicity was lymphopenia (35%) and thrombocytopenia (31%). Twenty-five patients experienced grade <or=2 sensory neuropathy (32), and 8% experienced grade 3 neurosensory toxicity. The overall response rate was 45% (40% on an intention to treat) including 10 complete remissions. Of 18 patients with FL, 9 responded with 4 complete response. The median time to treatment response for FL was 12 weeks, whereas the median time to treatment response for other subtypes of non-Hodgkin's lymphoma was only 4 weeks.


CONCLUSIONS
These data suggest that bortezomib has significant single agent activity in patients with FL, and that longer durations of treatment may improve overall response.
O'Connor
Owen A
OA
NYU Cancer Institute, NYU Langone Medical Center, New York, New York, USA. oo2130@columbia.edu
Portlock
Carol
C
Moskowitz
Craig
C
Hamlin
Paul
P
Straus
David
D
Gerecitano
John
J
Gonen
Mithat
M
Dumitrescu
Otilia
O
Sarasohn
Debra
D
Butos
John
J
Neylon
Ellen
E
Mac-Gregor Cortelli
Barbara
B
Blumel
Susan
S
Evens
Andrew M
AM
Zelenetz
Andrew D
AD
Wright
John
J
Cooper
Brenda
B
Winter
Jane
J
Vose
Julie
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008224:Lymphoma, Follicular / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000627:therapeutic use*; D012008:Recurrence; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib