RB but not R‐HCVAD is a feasible induction regimen prior to auto‐HCT in frontline MCL: results of SWOG Study S1106

Abstract

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 Southwesterm Oncology Group S1106 trial was designed to assess rituximab plushyperCVAD/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.

Bendamustine for patients with indolent B cell lymphoproliferative malignancies including chronic lymphocytic leukaemia – an updated meta‐analysis

“…Two ongoing trials were identified that were not completed. Nine trials fulfilled inclusion criteria and were included in the systematic review and in the meta‐analysis (Eichhorst et al , ; Flinn et al , ; Herold et al , ; Knauf et al , , ; Niederle et al , ; Rummel et al , , ; Michallet et al , ; Chen et al , , NCT00877006) (Fig ).…”

“…Median age of patients ranged between 58 and 74 years. Three trials included a population in which the median/mean age was below 60 years (Herold et al , ; Flinn et al , ; Chen et al , ). Three trials included patients with a median age above 65 years (Niederle et al , ; Rummel et al , ; Michallet et al , ).…”

“…Four trials included patients with CLL (Knauf et al , , ; Niederle et al , ; Eichhorst et al , ; Michallet et al , ), and five trials included patients with indolent lymphoma (Herold et al , ; Rummel et al , , ; Flinn et al , ; Chen et al , ), most of whom had follicular lymphoma, and patients with mantle cell lymphoma (about 20% of all patients), one trial included patients with mantle cell lymphoma (Chen et al , ) (Table ). Two trials included patients with relapsed or refractory disease (Niederle et al , ; Rummel et al , ); all other trials included newly diagnosed (first line) patients.…”

Phase 1–2 study of vorinostat (SAHA), cladribine and rituximab (SCR) in relapsed B‐cell non‐Hodgkin lymphoma and previously untreated mantle cell lymphoma

“…However, the response rates and PFS seen with the SCR regimen compare favourably with other less intensive induction regimens. For example, the CR rate with SCR was higher than that seen in prospective studies using BR (40%), R‐cladribine (52%), R‐CHOP (34–42%), and VR‐CAP (rituximab, cyclophosphamide, doxorubicin and prednisone plus bortezomib; 53%) (Kluin‐Nelemans et al , ; Robak et al , ; Chen et al , ; Le Gouill et al , ; Visco et al , ; Chang et al , ; Ruan et al , ; Tam et al , ). Furthermore, although MRD testing was only available for 14 responding patients, all were MRD‐negative after induction.…”

R‐High‐CHOP/CHASER/LEED with autologous stem cell transplantation in newly diagnosed mantle cell lymphoma: JCOG0406 STUDY

“…As highly efficient harvest of auto‐PBSC was observed during the first CHASER (data not shown), it is possible that a greater number of patients may proceed to ASCT if the harvest of auto‐PBSC is initiated during the first CHASER. Possibility that the harvest of auto‐PBSC in the early period of intensive induction chemotherapy may result in a highly efficient harvest was suggested in a recent phase II study . In that randomized phase II study by the Southwest Oncology Group that compared HyperCVAD/MA with rituximab and bendamustine with rituximab (S1106 study), stem cell collection was planned and carried out after the 3rd of 4 HyperCVAD/MA cycles.…”