Population Survey of Mantle Cell Lymphoma (MCL) in British Columbia (BC) – A Heterogeneous Disorder with Improved Outcomes in the Modern Era
Authors: den Brok Wendie-lou D. , Song Kevin W. , OLeary Hilary M. , Klasa Richard , Savage Kerry J. , Shenkier Tamara , Villa Diego , Slack Graham W. , Shepherd John D. , Gascoyne Randy D. , Connors Joseph M. , Sehn Laurie H. 
Published: October 2019

Abstract
Abstract 1602

Introduction:
MCL presents a therapeutic challenge remaining incurable with standard therapy. Most pts exhibit aggressive behaving advanced (adv) stage disease at diagnosis and require multi-agent chemotherapy, while others may have an indolent course. Improved outcomes with rituximab (R) and autologous stem cell transplant (ASCT) have been reported for select pts within the context of small clinical trials. In the province of BC, a new policy was introduced in 2003 recommending upfront ASCT for all eligible pts with adv stage MCL. This largely coincided with the availability of R which was included in the protocol: 6 cycles R-CHOP induction followed by ASCT and 2 cycles R maintenance (R weekly × 4 at 2 and 6 mo). The aim of this study was to review the clinical profile of MCL within a non-selected population of pts and to evaluate outcomes before and after this policy change.

Methods:
Using the BC Cancer Agency Centre for Lymphoid Cancer database, we identified all pts diagnosed with MCL between Jan 1990 and Dec 2010. Pathology was centrally reviewed and clinical data was retrieved from the database and medical records. Within this grp, we identified a SCT eligible cohort (<66 y with adv stage, excluding pts initially observed) and outcomes were evaluated in the pre and post SCT era, based on the policy initiation date of Jan 2003.

Results:
In total 535 pts were identified, median age 67 y (range 22–94), 71% male, 88% adv stage, 8% limited (lim) stage (stage I/II, bulk <10 cm, no B-sx), 4% stage unknown. Pathology: 55% diffuse, 25% nodular, 6% mantle zone, 14% blastoid. Primary treatment information was available on 511/535 (96%) pts and was as follows: 335 (66%) various chemo regimens (59% anthracycline-based); 58 (11%) induction chemo followed by SCT (55 auto, 3 allo), 67 (13%) observed, 30 (6%) XRT and/or surgery alone, and 21 (4%) were too frail or refused therapy. Overall, 163/511 (32%) received R as part of initial therapy. With a median f/up for living pts of 53 mo (range 1–251), the median OS and PFS for the entire cohort was 3.1 y and 1.3 y, respectively. Blastoid variant was associated with a poorer outcome compared with other histologies (p<0.001). Lim stage pts (n=45) had a more favorable outcome than adv stage pts (n=469), median OS 7.7 y v 2.9 y (p=0.0001) and median PFS 3.4 y v 1.2 y (p=0.0002). Pts initially observed (n=67) had a similar outcome compared with those receiving any initial treatment (n=423), median OS 4.4 y v 3.2 y (p=0.24). Twenty-nine pts were identified as long-term survivors (OS >10 y), mainly diagnosed prior to SCT policy (where f/up is shorter) and were treated with various regimens. Within this grp, median age was 57 y and 28% had lim stage, but no obvious associated clinical parameters were noted. To evaluate the impact of initial SCT, we compared outcomes in SCT eligible pts (n=179), diagnosed prior to (pre-SCT, n=93) and following its introduction in 2003 (post-SCT, n=86). Clinical characteristics were comparable between the pre-SCT and post-SCT grps; median age 56 y, MIPI score 20% high, 28% intermed, 52% low. Within the pre-SCT grp, initial treatment included CHOP-like chemo (n=46), intensive chemo (n=20), non-anthracycline-based tx (n=20) and SCT (n=3, 1 allo; received prior to policy initiation), median f/up 11 y. Within the post-SCT grp, initial treatment included SCT (n=50, 2 allo), CHOP-like chemo (n=31), non-anthracycline-based tx (n=5), median f/up 4.4 y. Thirty-six post-SCT pts did not undergo SCT (13 co-morbidities, 13 progressive disease during induction, 6 unknown/not offered, 4 declined). R was received by 8/93 (9%) pre-SCT pts and 81/86 (94%) post-SCT pts. Based on era of treatment, outcomes were significantly improved in the post-SCT grp compared with the pre-SCT grp, median OS not reached v 3.4 y, p=0.001 (5-y OS 58% v 34%) and median PFS 3.5 y v 1.3 y, p<0.001 (5-y PFS 38% v 16%). (see figure) An analysis based on actual initial treatment received (SCT v no-SCT), demonstrates favorable outcome associated with SCT (5-y OS 78% v 31%; 5-y PFS 55% v 15%).

Conclusion:
Outcomes for MCL have significantly improved in the modern era following the introduction of upfront ASCT in BC. Availability of rituximab coincided with this policy change and likely contributed to this improvement. Similar to prior observations, a subset of pts with indolent behaving disease can be observed without impacting OS. Patients with limited stage disease have a more favorable outcome, but no survival plateau was noted.

Disclosures:
den Brok: F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Song:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. OLeary:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Klasa:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Savage:Roche: Research Funding. Shenkier:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Villa:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Slack:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Shepherd:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Gascoyne:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Connors:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Sehn:F. Hoffmann-La Roche (Roche Canada): Research Funding.