Results of the IELSG32 trial at a median follow-up of 88 months demonstrate that matrix followed by autologous transplant is associated with excellent survival and neurotolerability in patients with primary CNS lymphoma
Calimeri, T. Cwynarski, K. Pulczynski, E. Fox, C. P. Schorb, E. Steffanoni, S. Foppoli, M. Celico, C. Falautano, M. Nonis, A.
Calimeri, T.
Cwynarski, K.
Pulczynski, E.
Fox, C. P.
Schorb, E.
Steffanoni, S.
Foppoli, M.
Celico, C.
Falautano, M.
Nonis, A.
Citations
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Abstract
Introduction: The MATRix regimen (methotrexate, cytarabine,
thiotepa, rituximab) significantly improved outcome of pts with primary
CNS lymphoma (PCNSL) enrolled in the IELSG32 trial. At a median
follow-up of 40 months, both whole-brain irradiation (WBRT) and autologous transplantation (ASCT) were safe and equally effective. However, sound assessment of OS, late complications, incidence of secondary
tumors, and cognitive impairment requires longer follow-up. Herein, we
report the results of IELSG32 trial at a median follow-up of 88 (IQR 77-
99) months.
Methods: pts with untreated PCNSL (18-70 years) were randomly as signed to methotrexate-cytarabine (arm A), or arm A + rituximab (arm
B), or arm B + thiotepa (MATRix; arm C). A second randomization assigned pts with responsive/stable disease after induction to WBRT (arm
D) or BCNU-Thiotepa-conditioning ASCT (arm E). Treatment effect on
cognitive functions and quality of life (QoL) were addressed by IPCG
tests panel and EORTC-QLQ.
Results: 219 pts were randomized (arm A 75; B 69; C 75). After induction, 167 had responsive/stable disease: 118 were assigned to WBRT
(59) or ASCT (59) while 49 were excluded from 2nd randomization. Fifteen pts died of iatrogenic toxicity; 87 (40%) pts remain relapse-free (A
17; B 28; C 42), 14 of them died of unrelated causes (Table 1). Among
117 relapsing pts, 96 died of PCNSL, 7 of salvage therapy complications.
Eight pts developed second cancers at 48-96 months from WBRT (5) or
ASCT (3). Second tumors and deaths in relapse-free pts or during salvage were not significantly related to treatments (Table 1). Neuropsychological tests showed a significant impairment in attentiveness and
executive functions in the WBRT arm, while transplanted pts had a significant improvement in these functions as well as memory and QoL.
Pts treated with MATRix showed significantly better PFS (7-year: 20%
arm A; 29% arm B; 52% arm C) and OS (7-year: 26% arm A; 37% arm
B; 56% arm C). No significant differences were seen between the consolidation arms for either PFS (7-yr: 55% arm D; 50% arm E) or OS (7-
yr: 63% vs 57%). Pts treated with MATRix and consolidation had a 7-yr
OS of 70%, without a difference between WBRT and ASCT.
Conclusions: MATRix was linked to excellent long-lasting outcome.
WBRT and ASCT have comparable efficacy. MATRix and ASCT did
not result in higher non-relapse mortality or second tumors onset. WBRT
led to impairment of specific cognitive functions.
Authors
Calimeri, T.
Cwynarski, K.
Pulczynski, E.
Fox, C. P.
Schorb, E.
Steffanoni, S.
Foppoli, M.
Celico, C.
Falautano, M.
Nonis, A.
La Rosee, P.
Binder, M.
Fabbri, A.
Ilariucci, F.
Krampera, M.
Roth, A.
Hemmaway, C.
Johnson, P. W.
Linton, Kim M
Pukrop, T.
Gorlov, J.
Balzarotti, M.
Hess, G.
Keller, U.
Stilgenbauer, S.
Panse, J.
Tucci, A.
Orsucci, L.
Pisani, F.
Zanni, M.
Krause, S. W.
Schmoll, H. J.
Hertenstein, B.
Rummel, M.
Smith, J.
Thurner, L.
Cabras, G.
Pennese, E.
Ponzoni, M.
Deckert, M.
Politi, L. S.
Finke, J.
Ferranti, A.
Cozens, K.
Burger, E.
Ielmini, N.
Cavalli, F.
Zucca, E.
Illerhaus, G.
Ferreri, A. J. M.
Cwynarski, K.
Pulczynski, E.
Fox, C. P.
Schorb, E.
Steffanoni, S.
Foppoli, M.
Celico, C.
Falautano, M.
Nonis, A.
La Rosee, P.
Binder, M.
Fabbri, A.
Ilariucci, F.
Krampera, M.
Roth, A.
Hemmaway, C.
Johnson, P. W.
Linton, Kim M
Pukrop, T.
Gorlov, J.
Balzarotti, M.
Hess, G.
Keller, U.
Stilgenbauer, S.
Panse, J.
Tucci, A.
Orsucci, L.
Pisani, F.
Zanni, M.
Krause, S. W.
Schmoll, H. J.
Hertenstein, B.
Rummel, M.
Smith, J.
Thurner, L.
Cabras, G.
Pennese, E.
Ponzoni, M.
Deckert, M.
Politi, L. S.
Finke, J.
Ferranti, A.
Cozens, K.
Burger, E.
Ielmini, N.
Cavalli, F.
Zucca, E.
Illerhaus, G.
Ferreri, A. J. M.
Description
Date
2021
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Calimeri T, Cwynarski K, Pulczynski E, Fox CP, Schorb E, Steffanoni S, et al. RESULTS OF THE IELSG32 TRIAL AT A MEDIAN FOLLOW-UP OF 88 MONTHS DEMONSTRATE THAT MATRIX FOLLOWED BY AUTOLOGOUS TRANSPLANT IS ASSOCIATED WITH EXCELLENT SURVIVAL AND NEUROTOLERABILITY IN PATIENTS WITH PRIMARY CNS LYMPHOMA. Haematologica. 2021;106(10):33-.