Bortezomib-Bendamustine-Dexamethasone in patients with relapsed/refractory Multiple Myeloma (MM) shows
marked efficacy and is well tolerated, but assessment of PNP symptoms shows significant discrepancies between
patients and physicians
Heinz Ludwig1, Hedwig Kasparu2, Werner Linkesch3, Josef Thaler4, Richard Greil5, Clemens Leitgeb1, Daniel Heintel1, Elisabeth Rauch1,
Niklas Zojer1, Ludek Pour6 and Zdenek Adam7
Background
Results
T R
ol e
e s
r u
a l
n ts
ce
Bendamustine, an alkylating drug with purine like activities may exert synergistic activity in
Median follow up was 7.5 (range: 1.28 ­ 15.3) months, myeloma responses are
Patient self reported neuropathic
combination with bortezomib. Here we analyze the efficacy and tolerance of bortezomib-
shown below.
symptoms at baseline: G1-2: 57%
bendamustine-dexamethasone with particular focus on possible discrepancies between
Median time to best response was 3.7 (range: 1 - 8.6) months.
G3-4: 17%. This pattern remained
patient and physician assessed neuropathic symptoms.
stable from cycle 1 to 4.
Response to BBD
Response category
Number (percentage)
Median PFS: 10.9 months.
Physician assessed neurotoxicity
CR
7 (13%)
Median OS: 15.2 months.
at
baseline:
G1-2:
18%.
This
VGPR
7 (13%)
Median TTP in high risk:
pattern
remained
constant
in
Patients and Methods
PR
17 (33%)
10.9 months and 12.2
almost all patients with only 2
months in standard risk
patients developing G3 PNP.
MR
12 (23%)
57 patients with relapsed/refractory MM have been enrolled. Patient characteristics are
SD
9 (17%)
patients.
shown below. Full data documentation for response evaluation ( 2 cycles) is available for
ORR (CR-PR)
31/51 (60%)
52 patients.
ORR (CR-MR)
43/52 (83%)
Progression free survival
Treatment regimen: Bendamustine 70 mg/m2 day 1+4, Bortezomib 1.3 mg/m2 days 1, 4, 8
Previously exposed to
CR-PR: 19 (58%)
.01
and 11, Dexamethasone 20 mg on days 1, 4, 8 and 11, repeated every 4 weeks.
bortezomib (33 evaluable)
CR-MR: 27 (82%)
Toxicity was assessed in 57 patients
Previously exposed to
CR-PR: 13 (50%)
.8
The FACT-GOG/NTX instrument was used for self assessment of neuropathic pain by
0
Hematological
Grade 3
Grade 4/5
Lenalidomide (26 evaluable)
CR-MR: 19 (73%)
ility
patients.
b
Anemia
7 (12%)
2 (4%) /0
a
.6
b
0
ro
Leucopenia
7 (12%)
1 (2%) /0
Response in cytogenetic standard and
P
.4
Thrombocytopenia
12 (21%)
9 (16%) /0
0
Patient characteristics
high risk patients
.40
Number of patients
57
Non-Hematological
Grade 1/2
Grade 3
Grade 4/5
Response
Standard
High risk
.20
Age, median (range)
64 (40-86)
Infection / Sepsis
23 (40)
3 (5%)
2 (4%) / 2 (4%)
Risk (n=16)
(n=19)
Gender, male/female
23/34
Herpes zoster infection
1 (2%)
3 (5%)
-
CR
1 (6%)
2 (11%)
.00
ISS Stage I
17
Diarrhea
11 (19%)
4 (7%)
-
VGPR
3 (19%)
3 (16%)
0
100
200
300
400
II
22
Constipation
15 (26%)
3 (5%)
-
PR
7 (44%)
4 (21%)
Days
III
18
Nausea, emesis
19 (33%)
-
-
CR-PR
11 (68.8%)
11 (57.9%)
ECOG 01 / 2
55/2
Polyneuropathy
21 (37%)
2 (4%)
-
MR
2 (13%)
6 (32%)
Prior treatment lines
Abdominal pain
7 (12%)
1 (2%)
-
SD
3 (19%)
4 (21%)
1-2
34
TTP in standard and high
Retinal detachment with hemorrhagia
-
-
1 (2%) /0
3-4
18
risk patients
Anaphylactic reaction to bendamustine
-
1 (2%)
-
Overall survival
5
5
.0
.0
1
1
Prior exposure to bortezomib
35
Prior exposure to lenalidomide
28
.8
.8
Conclusions
0
0
ility
ility
b
b
.6
.6
The BBD regimen yielded high response rates (58%) and a long PFS (10.9 months)
a
a
0
0
b
b
in heavily pretreated myeloma patients.
ro
ro
P
P
.4
.4
Affiliations
0
0
BBD was remarkably active in patients preexposed to bortezomib (58%) and
lenalidomide (50%).
1
.2
.2
Dept. of Internal Medicine I, Centre of Oncology and Hematology, Wilhelminenhospital, Vienna; 2Dept. of Internal
0
0
Medicine, Hospital Elisabethinen, Linz , Austria; 3Dept. of Hematology, Medical University, Graz, Austria; 4Dept. of
Patient self assessment of neuropathic symptoms revealed a higher incidence of
High risk
Internal Medicine IV, Hospital Wels-Grieskirchen, Wels, Austria; 5Salzburger Universitätsklinikum, Salzburg,
G1-2 and G3-4 symptoms than physician assessment.
.0
.0
Austria; 6University Hospital Brno, Brno, Czech Republic; 7Dept. of Internal Medicine - Hematooncology, University
0
0
Standard risk
Hospital, Brno, Czech Republic
Physician assessment of neurotoxicity seem to underestimate neurologic symptoms
0
100
200
300
400
0
100
200
300
400
associated with disease or neurotoxic treatment.
Days
Days

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