12th Congress of the European Hematology ... - Haematologica

0409
FRACTIONATED RADIOIMMUNOTHERAPY IN NHL WITH DOTA-CONJUGATED, HUMANIZED
ANTI-CD22 EPRATUZUMAB AT HIGH CUMULATIVE 90Y DOSES
F. Morschhauser, 1 F. Kraeber-Bodere, 2 M.-O. Petillon, 1 J.-F. Chatal, 2
J.-L. Harousseau, 3 H. Horne, 4 N. Teoh,4 W.A. Wegener, 4
D.M. Goldenberg 4
1 Centre Hospitalier Universitaire, LILLE, France; 2 Institut de Biologie, INSERM,
Research, NANTES, France; 3 Service d'Hematologie, Centre Hospitalie,
NANTES, France; 4 Immunomedics, Inc, MORRIS PLAINS, NJ, USA
Background. The advantages of fractionated delivery of external radiation
therapy may also apply to radioimmunotherapy. Aims. A phase I/II,
multi-center, dose-escalation trial was undertaken to determine the maximum
tolerated dose (MTD) for 2 or 3 weekly infusions of 90Yepratuzumab
in non-Hodgkin's lymphoma (NHL). Methods. Patients (pts)
with B-cell NHL who failed >1 regimen of standard chemotherapy were
eligible if they had 100,000
cells/mm 3 , and measurable disease by CT with no single mass >10 cm.
The 90Y dose was escalated separately in increments of 2.5 mCi/m 2
(92.5 MBq/m 2 ) in cohorts of 3-6 pts with or without prior bone marrow
transplant (BMT) until 2 occurrences of dose limiting toxicity (DLT).
Results. Fifty-five pts (31 male, 24 female; median age 63) with a median
of 3 prior therapies have now completed treatment. Therapy was
well tolerated, and other than hematological DLT, no serious adverse
events were considered treatment-related. For 17 pts with prior BMT,
escalation stopped with 2 DLTs (platelet recovery delayed >12 wks) at
10 mCi/m2 total dose (5.0 mCi/m 2 ×2 wk). For 38 pts without prior BMT,
no DLTs have yet occurred at 45 mCi/m 2 total dose (15 mCi/m 2 ×3 wk),
the highest level currently administered. Of 44 pts with evaluated treatment
responses, 23 (52%) had an objective response (OR) by International
Working Group (IWG) criteria, across all histologies [follicular NHL,
11/20 (55%); DLBCL, 3/9 (33%); mantle cell, 6/12 (50%), marginal zone,
3/3 (100%)], and including pts after prior BMT (7/17, 41%), or pts not
responding to the last rituximab-containing regimen (6/9, 67%). Most
ORs were complete responses (CR/CRu, 17/23, 74%), and with longterm
follow-up now available in 11 CR/CRu responders, 8 pts had
responses >6 mo, including 3 pts with continuing response >1 yr. OR
rates increased at higher cumulative dose for the 44 patients currently
evaluated [5-10 mCi/m 2 , 7/17 (41%), 15-20 mCi/m 2 , 7/12 (58%), 22.5-
37.5 mCi/m2, 9/15 (60%)] and remain to be determined for other pts currently
being evaluated, including those who completed treatment at the
highest cumulative doses, 40 and 45 mCi/m 2 . Conclusions. Fractionated
radioimmunotherapy with epratuzumab appears feasible and safe,
achieving high response rates at cumulative 90Y doses several-fold higher
than the 32-mCi (1200-MBq) limit approved for a single dose of
Zevalin.
12 th Congress of the European Hematology Association
0410
HIGH CURE RATE OF ADULT BURKITT'S AND OTHER HIGH GRADE NHL BY THE
COMBINATION OF SHORT INTENSIVE CHEMOTHERAPY CYCLES WITH RITUXIMAB
D. Hoelzer, 1 W. Hiddemann, 2 A. Baumann, 2 H. Döhner, 2 U. Dührsen, 2
R. Fietkau, 2 M.-L. Hansmann, 1 A. Hüttmann, 2 S. Irmer, 2 S. Kaun, 3
M. Kneba, 2 A. Reichle, 2 M. Schmid, 2 I. Schmidt-Wolf, 2 E. Thiel, 4
J. Walewski, 5 N. Gökbuget1 1 J.W.Goethe University, FRANKFURT AM MAIN, Germany; 2 University Hospital,
MUNICH, Germany; 3 Klinikum Bremen Mitte, BREMEN, Germany;
4 University Hospital Charité, BERLIN, Germany; 5 The Maria Sklodowska-
Curie Memorial Canc, WARSAW, Poland
Survival rates for adults with Burkitt'S NHL and B-ALL were improved
by mostly childhood derived regimens with HDMTX, HD alkylators
and HDAC to CR rates of 80% and overall survival (OS) of 50-70%. Further
intensification of chemotherapy in other and our study group failed
to improve these results (B-NHL90 trial, Blood 100 (11), #595). Therefore
the GMALL study group invented in 2002 a new B-NHL protocol including
6x Rituximab 375 mg/m 2 before each chemo cycle and of two Rituximab
maintenance cycles. In addition two cycles HDAC 2 g/m 2 were
included. HDMTX was reduced from 3 to 1,5 g/m 2 in the protocol for
younger pts (55 yrs) (Figure 1).
Figure 1. Multicentre study to optimize therapy of B-ALL, Burkitt’s NHL and
other high-grade non-Hodgkin’s lymphoma in adults (GMALL-B-ALL/NHL
2002).
In this study 376 pts with high-grade B-NHL were enrolled between
09/02 and 12/06. 272 were evaluable for response after the first two
cycles. The median age was 38 (16-78) yrs; 23% (N=63) were older than
55 yrs. The distribution of subtypes was as follows: 115 Burkitt's NHL
(stage III-IV 52%, extranodal inv. 78%, aaIPI >1 47%), 70 mature B-ALL,
62 DLBCL (42 mediastinal, stage III-IV 63%, extranodal inv. 77%, aaIPI
>1 63%), 14 B-LBL and 11 LACL. The CR rate after two cycles was 90%
in Burkitt's NHL, 81% in B-ALL and 74% in DLBCL; death under therapy
occurred in 3%, 11% and 2% respectively. The OS at 3 yrs was 91%
for Burkitt's NHL, 79% for B-ALL and 91% for DLBCL in pts 15-55 yrs
and 84%, 39% and 67% (N=9) in pts >55 yrs. Since in elderly pts with
mature B-ALL CNS relapses were observed, HDAC will be included in
the future. In younger pts the overall CNS relapse rate was 0. There was
no difference in OS between pts with Burkitt (92%) vs Burkitt-like NHL
(86%). Since no prognostic factors could be identified in younger pts,
there was no need for SCT in CR1. Major grade III/IV toxicity was hematological
(28-37%) and mucositis (36%, 37%, 28% in cycles A1, B1, C1
respectively). Compared to the trial B-NHL90 with 270 pts the OS at 3
yrs improved significantly from 54% to 80% (p