Clinical activity of bortezomib in relapsed/refractory MALT lymphomas: results of a phase II study of the International Extranodal Lymphoma Study Group (IELSG).
BACKGROUND
The nuclear factor-kappa B activation in mucosa-associated lymphoid tissue (MALT) lymphoma pathogenesis provided the rationale for the evaluation of bortezomib in this malignancy.


METHODS
Thirty-two patients with relapsed/refractory MALT lymphoma were enrolled. Thirty-one patients received bortezomib 1.3 mg/m(2) i.v., on days 1, 4, 8, and 11, for up to six 21-day cycles.


RESULTS
Median age was 63 years (range, 37-82 years). Median number of prior therapies was 2 (range, 1-4). Nine patients had Ann Arbor stage I, 7 patients had stage II, and 16 patients had stage IV. Primary lymphoma localization was the stomach in 14 patients; multiple extranodal sites were present in 10 patients. Among the 29 patients assessable for response, the overall response rate was 48% [95% confidence interval (CI) 29% to 67%], with 9 complete and 5 partial responses. Nine patients experienced stable disease and six had disease progression during therapy. The most relevant adverse events were fatigue, thrombocytopenia, neutropenia, and peripheral neuropathy. After a median follow-up of 24 months, the median duration of response was not reached yet. Five deaths were reported, in two patients due to disease progression.


CONCLUSIONS
Bortezomib is active in relapsed MALT lymphomas. Further investigations to identify optimal bortezomib dose, schedule, and combination regimens are needed since the frequent detection of dose-limiting peripheral neuropathy.
Conconi
A
A
Department of Clinical and Experimental Medicine, Division of Hematology, AOU Maggiore della Carità, Amedeo Avogadro University of Eastern Piedmont, Novara. Electronic address: conconi@med.unipmn.it.
Martinelli
G
G
Division of Hematology-Oncology, European Institute of Oncology, Milan, Italy.
Lopez-Guillermo
A
A
Department of Hematology, Hospital Clínic, Barcelona, Spain.
Zinzani
P L
PL
Institute of Hematology and Medical Oncology 'L. e A. Seràgnoli', University of Bologna, Bologna.
Ferreri
A J M
AJM
Unit of Lymphoid Malignancies, Medical Oncology Unit, Department of Oncology, San Raffaele H Scientific Institute, Milan.
Rigacci
L
L
Department of Hematology, Careggi Hospital and University of Florence, Florence.
Devizzi
L
L
Cristina Gandini Medical Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Tumori, Milan.
Vitolo
U
U
SC Ematologia II, Azienda Ospedaliera e Universitaria San Giovanni Battista, Turin.
Luminari
S
S
Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena, Italy.
Cavalli
F
F
IOSI-Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Zucca
E
E
IOSI-Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D018442:Lymphoma, B-Cell, Marginal Zone / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D017211:Treatment Failure; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib