Bortezomib may be safely combined with Y-90-ibritumomab tiuxetan in patients with relapsed/refractory follicular non-Hodgkin lymphoma: a phase I trial of combined induction therapy and bortezomib consolidation.
Preclinical studies suggest that bortezomib, through inhibition of nuclear factor-κB (NF-κB) activation, may enhance the effects of radioimmunotherapy. This phase I trial was designed to determine the maximum tolerated dose (MTD) of weekly bortezomib induction combined with Y-90-ibritumomab tiuxetan followed at the time of count recovery by weekly bortezomib consolidation in patients with relapsed/refractory follicular or transformed non-Hodgkin lymphoma. Grade 3 or 4 toxicities were observed in eight of nine treated patients, and all but one of these toxicities were hematologic. One patient had grade 3 cardiotoxicity. A dose limiting toxicity (DLT) of grade 4 thrombocytopenia was observed in two of three patients treated with bortezomib at 1.6 mg/m(2), resulting in a MTD of 1.3 mg/m(2). The overall response rate was 89% (two complete response [CR], six partial response [PR], one stable disease [SD]), with a median progression-free survival of 6.5 months (range: 3-22.5+ months). A phase II trial at the MTD is under way to better define the toxicity and effectiveness of this regimen.
Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. royrupali@gmail.com
Rupali
R
Roy
Andrew M
AM
Evens
David
D
Patton
Lillia
L
Gallot
Annette
A
Larson
Alfred
A
Rademaker
Jeffrey
J
Cilley
Stewart
S
Spies
Daina
D
Variakojis
Leo I
LI
Gordon
Jane N
JN
Winter
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects / Q000379:methods; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology; D011719:Pyrazines / Q000627:therapeutic use*; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000379:methods; D012008:Recurrence; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D015021:Yttrium Radioisotopes; C422802:ibritumomab tiuxetan; D000069286:Bortezomib