| Autor: |
Kolstad, Arne, Laurell, Anna, Andersen, Niels S, Elonen, Erkki, Raty, Riikka, Pedersen, Lone Bredo, Bogsrud, Annik Trond Velde, Nordstrom, Marie, Gillström, Dorte Balle, Hansen, Per Boye, Bentzen, Hans, Fagerli, Unn-Merete, Meyer, Peter, Nilsson-Ehle, Herman, Jerkeman, Mats, Lehman, Anne Kristine, Lauritzen, Grete F, Sundstrom, Christer, Delabie, Jan, Karjaalainen-Lindsberg, Marja-Liisa, Ralfkiaer, Elisabeth, Ehinger, Mats, Geisler, Christian H. |
| Jazyk: |
angličtina |
| Rok vydání: |
2009 |
| Zdroj: |
Kolstad, A, Laurell, A, Andersen, N S, Elonen, E, Raty, R, Pedersen, L B, Bogsrud, A T V, Nordstrom, M, Gillström, D B, Hansen, P B, Bentzen, H, Fagerli, U-M, Meyer, P, Nilsson-Ehle, H, Jerkeman, M, Lehman, A K, Lauritzen, G F, Sundstrom, C, Delabie, J, Karjaalainen-Lindsberg, M-L, Ralfkiaer, E, Ehinger, M & Geisler, C H 2009, ' 90 y-Ibritumumab Tiuxetan (Zevalin®-BEAM/C with Autologous Stem Cell Support as Therapy for Advanced Mantle Cell Lymphoma.-Preliminary Results From the Third Nordic II Study (MCL3) ', 51 th Annual Meeting of the American Society of Hematology, New Orleans, United States, 05/12/2009-08/12/2009 . |
| Popis: |
The Nordic Lymphoma Group has since 1996 conducted three consecutive phase II trials for front-line treatment of MCL patients ≤ 65 years of age. The first protocol (MCL1) 1996-2000 introduced high-dose chemotherapy with autologous stem cell support (unpurged or ex vivo purged) as consolidation after 4 cycles of intensified CHOP (maxi-CHOP). The results were disappointing, as the majority of patients relapsed. 1 Being in CR pre-transplant was the most important factor for outcome. Hence, in the second trial (MCL2) 2000-2006 induction therapy was intensified by adding high-dose Ara-C and rituximab to the regimen. Compared to MCL1 this led to significant improvement of event-free and overall survival, and the rate of PCR negative stem cell grafts and bone marrow samples.2 Again, responders in less than CR pre-transplant had a significantly poorer outcome. We therefore made a further intensification for the MCL3 study (2006-2009) by adding 90Y-Ibritumomab tiuxetan (Zevalin ®) to the high-dose BEAC/BEAM to responders not in CR. Methods: As in the MCL1 and 2 studies newly diagnosed stage II-IV MCL patients ≤ 65 years were included. Induction treatment was identical to that of the MCL2 study with alternating cycles of maxi-CHOP-rituximab (3 cycles) and Ara-C-rituximab (3 cycles). Response evaluation was done after cycle 5. PET/CT was recommended, but could not influence the response evaluation, which was done according to the International Workshop criteria. Responders underwent in vivo purged harvest of stem cells after cycle 6 (Ara-C + 2 doses of rituximab). Patients in CRu or PR received a standard dose 90Y-Ibritumomab tiuxetan (0.4 mCi/kg) one week prior to the BEAM/BEAC, CR patients received BEAM/BEAC alone. Patients are followed by CT-scans, bone marrow and blood samples, including PCR for minimal residual disease or molecular relapse. For molecular relapse preemptive treatment with 4 standard doses of rituximab, as in the MCL2 study3, is given. Results: The planned accrual of 160 patients was reached in June 2009. The patient characteristics are similar to those of the MCL2 trial with a median age of 57 years (28-65), the majority male (80%) and in stage IV (89%) with bone marrow involvement (74%). The response rates pre-transplant so far compare favorably with data from MCL2 with 50% in CR, 18% in CRu, and 28% in PR. Only 4 out of 128 evaluable patients did not respond (3%) and there was one case (1%) of treatment-related mortality during induction therapy. While it is still too early to assess the impact of the 90Y-Ibritumomab tiuxetan on the progression-free survival, the side effects were similar to those of the MCL2 study including a treatment related mortality of 4%. Fifty-five patients in CRu or PR have so far been treated with 90Y-Ibritumomab tiuxetan, with no indication of any added toxicity. Only 12 out of 133 patients (10%) have not undergone transplant, 5 due to stem cell harvest failure, 3 due to toxicity and 4 due to non response to induction treatment. PET-scan prior to transplant was positive in 2% of CR patients, 20% of CRu patients and 54% of PR patients. Patients with a positive PET-scan pre-transplant had a 36% chance of achieving a molecular remission post-transplant, compared to 92% of cases with a negative PET-scan (pConclusion: The high response rates after induction treatment achieved in the MCL2 study are confirmed in the present study. Adding 90Y-Ibritumomab tiuxetan to high-dose chemotherapy for responding patients not in CR prior to transplant is feasible and does not increase toxicity. A negative PET-scan prior to transplant predicts for a molecular remission after the transplant.References:1. Andersen et al, Eur J Cancer, 2002, 38: 401-4082. Geisler et al, Blood, 2008, 112: 2687-26933. Andersen et al J Clin Oncol 2009 epub ahead of press |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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