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Clinical Trial
. 2016 Jan;172(2):208-18.
doi: 10.1111/bjh.13818. Epub 2015 Oct 22.

Phase II trial of R-CHOP plus bortezomib induction therapy followed by bortezomib maintenance for newly diagnosed mantle cell lymphoma: SWOG S0601

Brian G Till  1   2 , Hongli Li  3 , Steven H Bernstein  4 , Richard I Fisher  5 , W Richard Burack  4 , Lisa M Rimsza  6 , Justin D Floyd  7 , Marco A DaSilva  8 , Dennis F Moore Jr  9 , Olga Pozdnyakova  10 , Sonali M Smith  11 , Michael LeBlanc  3 , Jonathan W Friedberg  4
Affiliations
Clinical Trial

Phase II trial of R-CHOP plus bortezomib induction therapy followed by bortezomib maintenance for newly diagnosed mantle cell lymphoma: SWOG S0601

Brian G Till et al. Br J Haematol. 2016 Jan.

Abstract

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.

Keywords: chemotherapy; lymphoma; maintenance therapy; mantle cell lymphoma; proteasome inhibition.

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Conflict of interest statement

Authors’ Disclosures of Potential Conflicts of Interest

B.G.T. has received research funding from Roche/Genentech. R.I.F. is a consultant for Johnson & Johnson and MorphoSys AG.

Figures

Figure 1
Figure 1
CONSORT diagram of patients enrolled in S0601. VR-CHOP: bortezomib, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; ASCT: autologous stem cell transplantation
Figure 2
Figure 2
(A) PFS and (B) OS of the entire cohort
Figure 3
Figure 3
(A) PFS and (B) OS by MIPI score
Figure 4
Figure 4
(A) PFS and (B) OS by Ki-67 proliferation index from baseline tumor samples
See this image and copyright information in PMC

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