Hypercvad Induction Chemotherapy Is Associated with Higher Rates of Stem Cell Mobilization Failure in Mantle Cell Lymphoma ( MCL)
Authors: Salhotra Amandeep , Yuan Shan , Palmer Joycelynne , Aldoss Ibrahim , Tsai Ni-Chun , Paris Tanya , Forman Stephen J. , Chen Robert W 
Published: October 2019

Abstract
Background: MCL patients deemed fit for high dose regimens undergo induction therapy with rituximab and chemotherapy (HyperCVAD/CHOP/bendamustine) followed by consolidation with ASCT (autologous stem cell transplantation). R-HyperCVAD is a dose intense regimen with high response rates for MCL when used in the upfront setting (ORR 97%; CR 38%; Romaquera JE, JCO 2005). R-bendamustine and R-CHOP are contemporary regimens with similar efficacy (ORR 85-93%; Rummel MJ, Lancet 2013). In a recent randomized phase II trial (SWOG 1106) accrual to the HyperCVAD arm was stopped due to higher than expected rates of peripheral blood stem cell (PBSC) mobilization failure.
Methods: To assess the impact of these regimens on PBSC collection, we performed a retrospective analysis of newly diagnosed MCL patients undergoing induction chemotherapy with R-HyperCVAD versus R-CHOP/R-bendamustine and referred to transfusion medicine for PBSC collection prior to ASCT from 01/2009 to 12/2013. Patients were not allowed any salvage chemotherapy. The primary end point was successful stem cell collection defined as ability to collect ≥2.1 million CD34 cells/Kg. Secondary endpoints were number of days of apheresis, use of pleraxifor as mobilization salvage and total number of CD34+ cells collected.
Results: A total of 91 MCL patients were eligible for analysis (Table 1). Patients who received HyperCVAD were younger at the time of collection (median: 56 vs 62 years; p <0.01) and were referred for collection earlier (median time from diagnosis to collection start: 4.5 vs. 6.4 months; p<0.01). There were no other baseline differences between the two groups in terms of gender, bone marrow involvement, stage of disease at presentation and use of plerixafor. While the median number of apheresis days were comparable: 4 (range: 1-9) for the HyperCVAD group and 3 (range: 2-8) for the other group (p=0.21), 18% patients in the Hyper-CVAD group failed to collect adequate numbers of PBSC (defined as < 2.1 ×10 6/Kg) compared to 4% in the other group (p=0.05). Additionally, the median number of CD34+ cells collected was lower in HyperCVAD group (p=0.05). After adjusting for baseline differences in age and timing of collection, for a patient who received HyperCVAD, the odds of failing to collect were 7.28 times higher (95% CI: 1.01, 52.57) than the odds for a patient who received a non-HyperCVAD induction regimen (p=0.05).
Ultimately, 81/91 (89%) patients proceeded to high dose chemotherapy and ASCT [82% in HyperCVAD versus 96% in non-HyperCVAD (p=0.06)]. Four of the remaining 10 patients with mobilization failure (all from HyperCVAD arm) proceeded to Allogeneic HCT, the remaining 6 patients did not receive any further treatment.
Conclusion: Patients with MCL receiving R-HyperCVAD chemotherapy in the frontline setting have a significantly higher rate of PBSC mobilization failure and collect significantly fewer CD34+ PBSCs when compared to patients treated with comparable regimens. R-HyperCVAD should be used with caution in patients with newly diagnosed MCL who are eligible for ASCT. Some patients failing mobilization may be salvaged with use of plerixafor.
Table 1: Patient, Transplant Characteristics Variable Hyper-CVAD, n=45Median (Range)N (%) Other, n=46Median (Range)N (%) Patient Gender Female Male 9 (20) 36 (80) 12 (26) 34 (74) Age at Collection Completion (years) 56 (40 – 68) 62 (36 – 74) Time from Diagnosis to Start of Collection (months) 4.5 (2.3 – 65.3) 6.4 (3.9 – 69.4) Stage at Diagnosis I II III IV 1 (2) 3 (7) 2 (4) 39 (87) 2 (4) 1 (2) 6 (13) 37 (81) Bone Marrow Involvement at Diagnosis No Yes Not Done 9 (20) 35 (78) 1 (2) 13 (28) 32 (70) 1 (2) Treatment after Chemotherapy Auto Transplant Allo Transplant No Transplant 37 (82) 4 (9) 4 (9) 44 (96) 0 (0) 2 (4) Mozobil Era (08/16/2009) Pre Post 8 (18) 37 (82) 3 (7) 43 (93) Mozobil Usage No Yes 29 (64) 16 (36) 30 (65) 16 (35) Number of Collections 4 (1 – 9) 3 (2 – 8) Total CD34 4.5 (0.3 – 100.5) 5.3 (0.7 – 76.6) Total CD34 (Failure Rate) < 2.1 >/= 2.1 8 (18) 37 (82) 2 (4) 44 (96)

Disclosures
Chen: Seattle Genetics: Honoraria, Research Funding, Speakers Bureau.