Chen Robert W, Li Hongli, Bernstein Steven H, Kahwash Samir, Rimsza Lisa M, Forman Stephen J, Constine Louis, Shea Thomas C, Cashen Amanda F, Blum Kristie A, Fenske Timothy S, Barr Paul M, Phillips Tycel, Leblanc Michael, Fisher Richard I, Cheson Bruce D, Smith Sonali M, Faham Malek, Wilkins Jennifer, Leonard John P, Kahl Brad S, Friedberg Jonathan W
City of Hope, Duarte, CA, USA.
SWOG Statistical Center, Seattle, WA, USA.
Br J Haematol. 2017 Mar;176(5):759-769. doi: 10.1111/bjh.14480. Epub 2016 Dec 19.
Aggressive induction chemotherapy followed by autologous haematopoietic stem cell transplant (auto-HCT) is effective for younger patients with mantle cell lymphoma (MCL). However, the optimal induction regimen is widely debated. The Southwestern Oncology Group S1106 trial was designed to assess rituximab plus hyperCVAD/MTX/ARAC (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone, alternating with high dose cytarabine and methotrexate) (RH) versus rituximab plus bendamustine (RB) in a randomized phase II trial to select a pre-transplant induction regimen for future development. Patients had previously untreated stage III, IV, or bulky stage II MCL and received either 4 cycles of RH or 6 cycles of RB, followed by auto-HCT. Fifty-three of a planned 160 patients were accrued; an unacceptably high mobilization failure rate (29%) on the RH arm prompted premature study closure. The estimated 2-year progression-free survival (PFS) was 81% vs. 82% and overall survival (OS) was 87% vs. 88% for RB and RH, respectively. RH is not an ideal platform for future multi-centre transplant trials in MCL. RB achieved a 2-year PFS of 81% and a 78% MRD negative rate. Premature closure of the study limited the sample size and the precision of PFS estimates and MRD rates. However, RB can achieve a deep remission and could be a platform for future trials in MCL.
对于年轻的套细胞淋巴瘤(MCL)患者,积极的诱导化疗后进行自体造血干细胞移植(auto-HCT)是有效的。然而,最佳诱导方案存在广泛争议。西南肿瘤协作组S1106试验旨在通过一项随机II期试验评估利妥昔单抗联合hyperCVAD/MTX/ARAC(超分割环磷酰胺、长春新碱、阿霉素和地塞米松,与高剂量阿糖胞苷和甲氨蝶呤交替使用)(RH)与利妥昔单抗联合苯达莫司汀(RB),以选择一种用于未来研究的移植前诱导方案。患者为先前未经治疗的III期、IV期或大肿块II期MCL,接受4个周期的RH或6个周期的RB治疗,随后进行auto-HCT。计划招募的160名患者中有53名入组;RH组不可接受的高动员失败率(29%)促使研究提前结束。RB组和RH组的估计2年无进展生存期(PFS)分别为81%和82%,总生存期(OS)分别为87%和88%。RH不是未来MCL多中心移植试验的理想方案。RB组的2年PFS为81%,微小残留病(MRD)阴性率为78%。研究提前结束限制了样本量以及PFS估计和MRD率的精确性。然而,RB可以实现深度缓解,可能成为未来MCL试验的一个方案。