Abstract

Background: We previously reported substantial activity with single-agent bortezomib (VELCADE®; Vc) in patients (pts) with relapsed or refractory MCL in the PINNACLE study (

JCO
2006
;
24
:
4867
–74
), which resulted in approval of Vc for MCL pts following ≥1 prior therapy. All pts have now completed treatment. Here we report updated time-to-event data in all pts, and by response category, with extended follow-up.

Methods: 155 pts (median age 65 yrs; 55%/41%/4% with 1/2/≥3 prior therapies; 77% Stage IV MCL; 55% positive bone marrow) received Vc 1.3 mg/m2 on days 1, 4, 8, and 11 of 21-day cycles; of these, 141 were response-evaluable. Response and progression were determined by modified International Workshop Response Criteria using independent radiology review.

Results: After a median follow-up of 26.4 mo, 55 pts (35%) remained in follow-up; 93 (60%) had died, 2 (1%) had withdrawn consent, and 5 (3%) were lost to follow-up. Pts received a median of 4 treatment cycles (range 1–21; 8 in responding pts). Median time to first response was 1.3 months. Median duration of response (DOR) was 9.2 mo in all responders and has not been reached in pts achieving CR/CRu. Median time to progression (TTP), time to next therapy (TTNT; first Vc dose to start of next therapy), and overall survival (OS) are shown in the table for all pts and by response.

Survival rate at 12-mo was 69% overall and 91% in responding pts. In pts refractory to their last therapy (no response or response with TTP <6 mo; n=58), median DOR was 5.9 mo, median TTP was 3.9 mo, median TTNT was 4.6 mo, and median survival was 17.3 mo. Safety profile was similar to previously reported; most common grade ≥3 AEs were peripheral neuropathy (13%), fatigue (12%), and thrombocytopenia (11%). The most common AE resulting in Vc discontinuation was peripheral neuropathy (10%). Twelve (8%) pts died on-study, including 5 (3%) considered related to Vc.

Conclusions: Vc provides durable responses plus prolonged time off-therapy and survival in responding pts, suggesting substantial clinical benefit in relapsed/refractory MCL.

Median TTP, TTNT, and OS (months) in all pts and by response

All pts (N=155)Responders (N=45)CR/CRu (N=11)PR (N=34)SD (N=52)PD (N=34)
NE, not estimable 
TTP 6.7 12.4 NE 9.1 6.9 1.2 
TTNT 7.4 14.3 23.9 13.3 7.0 2.3 
OS 23.5 35.4 36.0 35.1 27.8 13.7 
All pts (N=155)Responders (N=45)CR/CRu (N=11)PR (N=34)SD (N=52)PD (N=34)
NE, not estimable 
TTP 6.7 12.4 NE 9.1 6.9 1.2 
TTNT 7.4 14.3 23.9 13.3 7.0 2.3 
OS 23.5 35.4 36.0 35.1 27.8 13.7 

Author notes

Disclosure:Employment: Millennium (H Shi, A Boral). Consultancy: Millennium, Genentech (A Goy); Millennium, J&J (J Leonard); Millennium, Celgene (S Lonial); Genentech, GSK, Millennium (R Fisher); Millennium (S Bernstein). Ownership Interests:; Celgene, Amgen (A Krishnan); Millennium (H Shi, A Boral). Research Funding: Millennium (B Kahl, J Leonard, S Lonial, O O’Connor). Honoraria Information: Millennium, Celgene (E Epner); Celgene (A Krishnan); Millennium, J&J (J Leonard); Genentech, GSK, Millennium (R Fisher); Millennium (O O’Connor); Millennium (S Bernstein). Membership Information: Millennium, Genentech (A Goy); Celgene, Genentech, Millennium (A Krishnan); Millennium (J Leonard, E Stadtmauer); Genentech, GSK, Millennium (R Fisher). Financial Information: Celgene, Amgen stock (A Krishnan).