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Five-year outcomes of the S1106 study of R-hyper-CVAD vs R-bendamustine in transplant-eligible patients with mantle cell lymphoma
Kamdar, M., Li, H., Chen, R. W., Rimsza, L. M., Leblanc, M. L., Fenske, T. S., Shea, T. C., Barr, P. M., Phillips, T. J., Leonard, J. P., et al
Blood advances. 2019;3(20):3132-3135
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Autologous transplantation as consolidation for high risk aggressive T-cell non-Hodgkin lymphoma: a SWOG 9704 intergroup trial subgroup analysis
Al-Mansour, Z., Li, H., Cook, J. R., Constine, L. S., Couban, S., Stewart, D. A., Shea, T. C., Porcu, P., Winter, J. N., Kahl, B. S., et al
Leukemia & lymphoma. 2019;:1-8
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Abstract
Phase II data suggest a benefit to autotransplantation for aggressive T-cell non-Hodgkin lymphoma (T-NHL) in first remission; randomized trials have yet to validate this. We performed a retrospective analysis of aggressive T-NHL patients in the intergroup randomized consolidative autotransplant trial (SWOG 9704). Of the 370 enrolled, 40 had T-NHL: 12 were not randomized due to ineligibility (n = 1), choice (n = 2), or progression (n = 9), leaving 13 randomized to control and 15 to autologous stem cell transplantation (ASCT). Two ASCT patients refused transplant and one failed mobilization. The 5-year landmark PFS/OS estimates for ASCT vs. control groups were 40% vs. 38% (p = .56), and 40% vs. 45% (p = .98), respectively. No difference was seen based on IPI, or histologic subtype. Only 1/7 receiving BCNU-based therapy survived vs. 4/5 receiving TBI. Aggressive T-NHL autotransplanted in first remission did not appear to benefit from consolidative ASCT. This and the 30% who dropped out pre-randomization mostly to progression, suggests that improved induction regimens be developed.
PICO Summary
Population
Aggressive T-cell non-Hodgkin lymphoma patients, treated with five cycles of CHOP/CHOP-R administered every three weeks; those who achieved at least a partial response were eligible for randomization (n=28).
Intervention
One further cycle of CHOP/CHOP-R followed by autologous stem cell transplantation
Comparison
Three further cycles of CHOP/CHOP-R
Outcome
Aggressive T-NHL autotransplanted in first remission did not appear to benefit from consolidative ASCT. . The 5-year landmark PFS/OS estimates for ASCT vs. control groups were 40% vs. 38%, and 40% vs. 45%, respectively. No difference was seen based on IPI, or histologic subtype. Only 1/7 receiving BCNU-based therapy survived vs. 4/5 receiving TBI.
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RB but not R-HCVAD is a feasible induction regimen prior to auto-HCT in frontline MCL: results of SWOG Study S1106
Chen, R. W., Li, H., Bernstein, S. H., Kahwash, S., Rimsza, L. M., Forman, S. J., Constine, L., Shea, T. C., Cashen, A. F., Blum, K. A., et al
British Journal of Haematology. 2017;176(5):759-769
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 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. Copyright © 2016 John Wiley & Sons Ltd.
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Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704
Puvvada, S. D., Stiff, P. J., Leblanc, M., Cook, J. R., Couban, S., Leonard, J. P., Kahl, B., Marcellus, D., Shea, T. C., Winter, J. N., et al
British Journal of Haematology. 2016;174(5):686-91
Abstract
Double hit lymphoma (DHL) and double protein-expressing (MYC, BCL2) lymphomas (DPL) fare poorly with R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisolone); consolidative autologous stem cell transplant (ASCT) may improve outcomes. S9704, a phase III randomized study of CHOP +/-R with or without ASCT enabled evaluation of intensive consolidation. Immunohistochemistry (IHC) identified 27 of 198 patients (13.6%) with MYC overexpression; 20 (74%) harboured concurrent BCL2 overexpression. Four had DHL and 16 had DPL only. With median 127 months follow-up, there is a trend favouring outcomes after ASCT in DPL and MYC protein overexpressing patients, whereas all DHL patients have died irrespective of ASCT. Copyright © 2016 John Wiley & Sons Ltd.