Phase II trial of R-CHOP plus bortezomib induction therapy followed by bortezomib maintenance for newly diagnosed mantle cell lymphoma: SWOG S0601.
Bortezomib is active in mantle cell lymphoma (MCL), with approval in upfront and relapsed settings. Given inevitable recurrence following induction chemoimmunotherapy, maintenance approaches are a rational strategy to improve clinical outcomes. We conducted a phase II study to evaluate the safety and efficacy of six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) plus bortezomib (1.3 mg/m2 days 1 and 4 of 21 d cycles) followed by bortezomib maintenance (1.3 mg/m2 days 1, 4, 8, and 11 every 3 months for 2 years). Sixty-five eligible patients were enrolled. The treatment was well tolerated and toxicities were mainly haematological. The rate of grade ≥3 peripheral neuropathy was low (5%). With a median follow-up of 6.8 years, 2-year progression-free survival (PFS) was 62%, and 2-year overall survival (OS) was 85%. At 5 years, PFS was 28% and OS was 66%. MCL International Prognostic Index scores were significantly associated with 2-year PFS, but did not predict long-term (≥5-year) PFS. Baseline Ki-67 index was significantly associated with survival. Combination R-CHOP with bortezomib followed by maintenance bortezomib appears to improve outcomes compared historically with R-CHOP alone, with prolonged remissions in a subset of patients. These results suggest that inclusion of bortezomib with induction chemotherapy and/or maintenance is promising in MCL and warrants further exploration.
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|University of Washington Medical Center, Seattle, WA, USA.
Brian G
BG
Till
SWOG Statistical Center, Seattle, WA, USA.
Hongli
H
Li
James P. Wilmot Cancer Center, University of Rochester, Rochester, NY, USA.
Steven H
SH
Bernstein
Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA, USA.
Richard I
RI
Fisher
James P. Wilmot Cancer Center, University of Rochester, Rochester, NY, USA.
W Richard
WR
Burack
Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
Lisa M
LM
Rimsza
Heartland NCORP/Saint Francis Medical Center, Cape Girardeau, MO, USA.
Justin D
JD
Floyd
Southeast Cancer Consortium-Upstate NCORP/Kingsport Hem & Onc Associates, Kingsport, TN, USA.
Marco A
MA
DaSilva
Wichita NCORP/Cancer Center of Kansas, Wichita, KS, USA.
Dennis F
DF
Moore
Brigham and Women's Hospital, Boston, MA, USA.
Olga
O
Pozdnyakova
University of Chicago Hospitals, Chicago, IL, USA.
Sonali M
SM
Smith
SWOG Statistical Center, Seattle, WA, USA.
Michael
M
LeBlanc
James P. Wilmot Cancer Center, University of Rochester, Rochester, NY, USA.
Jonathan W
JW
Friedberg
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011379:Prognosis; D000069283:Rituximab; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D000069286:Bortezomib; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
chemotherapy; lymphoma; maintenance therapy; mantle cell lymphoma; proteasome inhibition