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Umberto Vitolo Ematologia
Città della Salute e della Scienza Torino
Linfomi
HODGKIN’S LYMPHOMA: Brentuximab Vedotin Background
Sasse, et al. Leuk & Lymph, 2013.
Median PFS: 9 months
Zinzani, et al. Haematologica, 2013.
Median PFS: 6.8 months
Median PFS: 5.6 months
Hodgkin’s Lymphoma Brentuximab Vedotin
BRENTUXIMAB VEDOTIN AS SINGLE AGENT IN REFRACTORY OR RELAPSED CD30-‐POSITIVE HODGKIN LYMPHOMA: THE FRENCH NAME PATIENT PROGRAM EXPERIENCE IN 241 PATIENTS
A Perrot et Al.
RetrospecJve trial from Jan 2011 and Jan 2014 241 pts with HD CD30+ Median age 30 ys (17-‐79) 49% primary refractory Prior CT: median 3 lines (1-‐13) 59% autologous transplant 16% allogenic transplant
Median of 6 BV cycles DisconJnuaJon rate: 92% (222 pts): -‐ 54% Progression of disease -‐ 25% transplant -‐ 5% Adverse event
CR PR ORR
AFTER 4 CYCLES 34% 26% 60%
END OF TREATMENT
24% 10% 34%
Median duraJon of response: 8 months (95% CI 6-‐14) Median PFS: 7 months (95% CI 6-‐8)
Hodgkin’s Lymphoma Brentuximab Vedotin
Causes of death Tot: 75 pts died
Lymphoma progression 68%
Concurrent illness 9%
Toxicity of addoJonal treatment 5%
No death linked to BV toxicity
Most common AE: -‐ Peripheral sensory neuropathy: 26 % g1-‐2, 2% g3-‐4 -‐ Anemia: 39% -‐ Thrombocytopenia: 27% -‐ Neutropenia: 23% (7% g3-‐4 infecJon) -‐ Diarrhea: 14%
Hodgkin’s Lymphoma Brentuximab Vedotin
This largest retrospecJve analysis supports the previously reported efficacy of BV in heavily pretreated CD30+ HL paJents with manageable toxicity. Due to a short duraJon of response, the use of autologous or allogeneic transplantaJon should be considered quickly in responder paJents as a consolidaJon approach to cure
the disease.
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Aggressive Lymphomas Standard Treatment
ü Rituximab schedule by gender
ü CNS Prophylaxis
ü Elderly Mantle Cell Lymphoma
ü Intensified salvage or condiWoning regimen
prior ASCT
Rituximab Schedule By Gender Increased rituximab doses eliminate increased risk of elderly male compared to female
patients with aggressive CD20+ B-cell lymphomas: Results from the SEXIE-R-CHOP-14 trial of the DSHNHL (Pfreundschuh M. et al.)
Objec&ve:
To invesWgate whether increasing the dose of rituximab in elderly males with DLBCL reduces their hazard compared to elderly females
Relative Risk Elderly Male vs. Female DLBCL Multivariate Analysis PFS
Without Rituximab With Rituximab
RICOVER-60 (n=612): 1.1*
NHL-B2 (n=142): 1.2
Pegfilgrastim (n=47): 0.2
all studies (n=801): 1.2*
* p<0.01
RICOVER-60 (n=610): 1.6*
RIC-No-RTh (n=164): 1.5
Pegfilgrastim (n=56): 3.5
all studies (n=830): 1.5*
Pfreundschuh et al., Blood 2014
n = 25 24 13 20
5.0 6.0
8.0 9.0
12.0 13.0 14.0 15.0 16.0 17.0 18.0 19.0 20.0
Ritu
xim
ab c
lear
ance
(ml/h
r)
7.0
11.0 10.0
p=0.005 p=0.004
p=0.015
♀ ♀ ♂ ♂ eldery patients young patients
Rituximab Schedule By Gender
RelaWve Rituximab Dose According to Sex
Months 0 5 10 15 20 25 30 35 40 45 50 0.0
0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
p=0.396
Females (n=120) Males (n=148)
74%
68% PFS OS
Months
MALE (148) FEMALE (120)
LEUKOCYTOPENIA 59% 85%
THROMBOCYTOPENIA 15% 32%
ANEMIA 16% 28%
No increase in rituximab-‐mediated toxiciWes
Days
Prop
orWo
n
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
Rituximab Schedule By Gender
Conclusions:
Rituximab 500 mg/m2 instead of 375 mg/m2 eliminates the increased risk of elderly males compared to females.
Since both young male and female patients have an unfavorable rituximab pharmacokinetics compared to elderly females, too, increasing the dose in these population should also result in a better outcome.
Whether 375 mg/m2 for elderly females is optimal, is unclear Suboptimally dosed rituximab can easily be beaten by other CD20 antibodies that are higher dosed and/or more
often given. Before we switch to new (and more expensive) CD20 antibodies, they must be shown to be superior to rituximab
in bona fide head-to-head comparisons (same dose & schedule).
E F S P F S O S HR [95%-CI]
RICOVER HR [95%-CI]
SEXIE-R HR [95%-CI]
RICOVER HR [95%-CI]
SEXIE-R HR [95%-CI]
RICOVER HR [95%-CI]
SEXIE-R
Elevated LDH 1.8
(p<0.001) 1.7
(p=0.170) 2.2
(p<0.001) 1.6
(p=0.238) 2.1
(p<0.001) 2.2
(p=0.107)
ECOG>1 1.8 (p=0.001) 1.1 (p=0.873) 1.7 (p=0.004) 1.2 (p=0.719) 1.9 (p=0.001) 1.3 (p=0.644)
Stages III-IV 1.5 (p=0.011) 1.2 (p=0.755) 1.5 (p=0.045) 1.2 (p=0.686) 1.5 (p=0.047) 1.1 (p=0.791)
>1 extra limph 1.0 (p=0.937) 1.9 (p=0.121) 1.1 (p=0.724) 2.0 (p=0.103) 1.1 (p=0.817) 1.5 (p=0.420)
Male vs. female 1.4 p=0.016
0.9 p=0.708
1.6 p=0.004
0.8 p=0.613
1.4 p=0.063
0.7 p=0.252
Rituximab Schedule By Gender
CNS Prophylaxis
P1087: CNS PROPHYLAXIS IN PATIENTS WITH DLBCL, ARE WE TREATING OURSELVES? A RESPONSE TO THE RECENT BCSH GUIDELINE
M Griffin1, et al. United Kingdom.
Analysis of all cases of CNS relapse over a 6 year period in North Trent, in a region that does not give CNS prophylaxis.
Which of them would have been eligible to CNS prophylaxis, according to GL? 620 de novo cases of DLBCL 13 CNS relapse (prevalence 2.1%) ü median age 53 ys (21-79) ü 10 male, 3 female ü 3 testicular DLBCL ü 9 IPI < 3
According to current BCSH GL only 4/13 pts would have received
CNS prophylaxis (3 testicular)
ü Majority of published data on CNS relapse are retrospective and of variable quality
ü Reduction of CNS relapses in the rituximab era (better initial disease control?) ü There is no reliable strategy for the identification of an individual at risk of CNS
relapse (with the possible exception of testicular disease) ü Benefit of IT-MTX prophylaxis alone is unproven.
Elderly Mantle Cell Lymphoma Randomized phase 3 study of rituximab, cyclophosphamide, doxorubicin, and
prednisone plus vincrisWne (R-‐CHOP) or bortezomib (VR-‐CAP) in newly diagnosed mantle cell lymphoma (MCL) paWents ineligible for bone marrow transplantaWon .
Cavalli F, et Al. Randomized, open-‐label, mulJ-‐center ph 3 study in newly diagnosed MCL paJents not
considered for BMT (NCT00722137)
Compare the efficacy and safety of R-‐CHOP vs VR-‐CAP (vincrisJne replaced with bortezomib)
Intent-‐to-‐treat (ITT) populaWon, N=487
R-‐CHOP N=244
VR-‐CAP N=243
Median age 66 (34–82) 65(26–8)
ECOG PS 0 / 1 / 2, %* 35 / 52 / 13
46 / 42 / 13
IPI score, 0–1 / 2 / 3 / 4–5, %*†
16 / 29 / 36 / 19
16 / 31 / 35 / 19
Disease stage at diagnosis, II / III / IV, %*†
7 / 20 / 74 6 / 20 / 75
Elevated LDH, % 35 36
Bone marrow + % 70 68
Extranodal +, % 56 57
)
Grade ≥3 AEs, %* (Safety populaWon) R-‐CHOP(n=242) VR-‐CAP (n=240)
At least one grade ≥3 AE 85 93 Neutropenia 67 85 Thrombocytopenia 6 57 Leukopenia 29 44 Lymphopenia 9 28 Anemia 14 15 Febrile neutropenia 14 15 Pneumonia 5 7 FaJgue 3 6 Peripheral sensory neuropathy 3 5 Diarrhea 2 5
Response-‐evaluable populaWon (n=457): CR+Cru: R-‐CHOP 42% vs VR-‐CAP 53% (p 0.007) ORR (CR+CRu+PR), %: R-‐CHOP 90% vs VR-‐CAP 92% (p 0.275) Median duraJon of response (CR+CRu+PR), mo: R-‐CHOP 15.1 vs VR-‐CAP 36.5 (p NA) Median Jme to iniJal response, mo: R-‐CHOP 1.6 vs VR-‐CAP 1.4 (p < 0.001)
ToxiciWes Analysis
Elderly Mantle Cell Lymphoma
Intensified Salvage Treatment Prior Asct R-‐ESHAP-‐LENALIDOMIDE AS SALVAGE THERAPY IN PATIENTS WITH RELAPSED OR REFRACTORY DIFFUSE LARGE B-‐CELL LYMPHOMA CANDIDATES TO STEM-‐CELL TRANSPLANTATION: UPDATED RESULTS OF A
PHASE IB GELTAMO STUDY A MarWn, et Al.
DLBCL
R-anthracylinerefractory
orrelapsed
Screening
Response
BEAMASCT
R=RituximabL=LenalidomideCycle=21 days
LR-ESHAPResponse
No further protocol treatment
CT-PET
CT
CT-PET
ResponseCT-PET
Follow-up
Cycle 1 Cycle 2 Cycle 3
PD or SD PD or SD
LR-ESHAP LR-ESHAP
R-‐ESHAP Rituximab: 375 mg/m2, d 1 or 5 Etoposide: 160 mg/m2 (40 mg/m2/d, d 1-‐4) CisplaWn: 100 mg/m2 (25 mg/m2/d, d 1-‐4) Ara-‐C: 2000 mg/m2 (d 5) Methilprednisolone: 2500 mg (500 mg /d, d1-‐5)
Lenalidomide (d 1-‐14 of every 21-‐d cycle) Dose level 1: 5 mg Dose level 2: 10 mg Dose level 3: 15 mg Dose level 4: 20 mg
Phase Ib escalaWng-‐dose mulWcentre trial
Primary objecWve : safety and determine the MTD of lenalidomide in combinaJon with R-‐ESHAP in pts with relapsed or refractory DLBCL candidates for ASCT
Secondary objecWves : To evaluate anJtumor acJvity, measured by CR and OR rates (determined by PET/CT), PFS and OS, to assess stem-‐cell mobilizaJon aner the salvage therapy, to measure the rate of paJents who achieve ASCT
N=19 N=18 N=17 N=14 (73,7%)
OUT OUT
CLINICAL CHARACTERISTICS:
19 pts, median age: 58 (23–70) Diagnosis: DLBCL 17 (89,5%)
Intermediate DLBCL/BL 2 (10,5%) 1-‐line treatment: R-‐CHOP-‐like 17 (89,5%)
Burkio-‐like protocols 2 (10,5%) IPI > 4: 5 (26,3%) DS: Primary refractory disease 13 (68,4%)
Early relapse 3 (15,8%) Late relapse 3 (15,8%)
Lenalidomide N DLT
(first cycle) PaWents failing first mobilizaWon
5 mg 3 0 / 3 0 / 3
10 mg 3 0 / 3 1 / 3
15 mg 4 11 / 4 2 / 4
10 mg (MTD) 9 0 / 9 2 / 9
Dose-‐limiWng toxicity
1Grade 3 facial angioedema
Intensified Salvage Treatment Prior Asct
RESPONSE ANALYSIS Aier
LR-‐ESHAP N (%)
Aier ASCT N (%)
Complete remission 8 (42) 8 (42) ParWal response 6 (32) 5* (26) Overall response 14 (74) 13 (68) Stable disease 1 (5) 0 Progression 3 (16) 1 (5) Not evaluated 1 (5) 5 (26) Total 60 60
Median FU: 11,9 months (5,9 – 30) Progression: 9 paJents (47%) Deaths: 7 paJents (lymphoma). No TRM. 1-‐year PFS: 61% 1-‐year OS: 63%
ü The MTD of lenalidomide in combinaWon with R-‐ESHAP is 10 mg
ü LR-‐ESHAP shows an acceptable safety profile and encouraging acWvity in rituximab-‐pretreated relapsed or refractory DLBCL paWents
ü Further invesWgaWon with this regimen is warranted
Intensified Salvage Treatment Prior Asct
Intensified Conditioning Regimen Prior Asct: Zevalin-B(F)EAM
Krishnan et al, JCO 26:90-5, 2008
89%
70%
• ASCT superior to convenJonal salvage in relapsing NHL
• High incidence of relapses aner ASCT in high risk pts
• Need to opJmize HD-‐CHT to improve the outcome post
ASCT
• Radioimmunotherapy with ZEVALIN produces high
response rate in relapsing NHL, also in pts pretreated
with Rituximab.
41 relapsed/resistant pts Median previous therapies 2 (1-‐6)
Day -‐14 -‐7 -‐5 -‐3 -‐21
90Y-‐Zevalin 0.4 mCi/kg Rituximab 250 mg/m2
VP/AraC Mel
TRANSPLANT
BCNU
-‐6 -‐4 -‐2
150 mg/m2
Rituximab 250 mg/mq
-‐1
65% 67.6%
12 progressions/relapses 8 deaths for lymphoma 1 alive with acWve disease
13 deaths: 1 aspergillosis + H1N1 1 encefaliWs 8 lymphoma
Median FU from salvage therapy Z-‐BEAM: 27 months Median FU from diagnosis: 66 months
Z-BEAM and ASCT:OS and PFS TOT: 37 PTS N° (%)
HISTOLOGY • FL (gI-‐II) • FL (gIII) • PML/DLBCL • MCL • NHL INDOLENT
9 5 18 3 2
24 14 49 8 5
STAGE • I • II • III-‐IV
0 9 28
0 24 76
LDH • NORMAL • UPPER THAN NORMAL • ND
21 15 1
57 42 1
TYPE OF DISEASE • RELAPSE • REFRACTORY
18 19
49 51
PREVIOUS THERAPY • 1 • ≥ 2
16 21
43 57
PREVIOUS RITUXIMAB • YES • NO
37 0
100 0
BEAM vs Z-BEAM: PFS
Intensified Conditioning Regimen Prior Asct: Zevalin-B(F)EAM
Indolent NHL: Sabrina Study SUBCUTANEOUS RITUXIMAB AND CHEMOTHERAPY ACHIEVES SIMILAR OVERALL RESPONSE RATES TO INTRAVENOUS RITUXIMAB IN FIRST-‐LINE FOLLICULAR LYMPHOMA: EFFICACY AND
SAFETY RESULTS OF THE PHASE III SABRINA STUDY. A Davies, et Al.
Two-‐stage phase III study of RSC 1400mg or RIV 375mg/m2 plus chemotherapy (≤8 cycles CHOP, or 8 cycles CVP every 3 weeks during inducJon (first cycle RIV on both arms) followed by RSC or RIV maintenance every 8 weeks in pts with FL. Primary objecWve: • efficacy data, ORR (CR + PR) at the end of inducJon treatment; • safety analyses In each arm, approximately 64% pts received CHOP and 36% received CVP chemotherapy
ORR CR
Rituximab sc (205) 83.4 % 32.7 %
Rituximab iv (205) 84.4 % 31.7 %
Indolent NHL: Sabrina Study
CONCLUSIONS: RSC demonstrated comparable ORR and CR rates with RIV. The safety profile of RSC and
RIV was similar and there were no new safety concerns with the SC formulaJon. Availability of RSC administraJon over approximately 5 minutes is expected to have a
posiJve impact on pt convenience and health care resource savings without compromising the anJ-‐lymphoma acJvity of rituximab.
Median follow-‐up 14.4 months, similar rates of AEs: 184/197 [93%] Rituximab SC vs 194/210 [92%] Rituximab IV
Serious Aes: 57 pts (29%) Rituximab SC and 55 pts (26%) Rituximab IV
Common haematological Aes: neutropenia and anaemia (both ≤5% of pts in each group)
Rituximab SC Rituximab IV
InfecJons 20/197 (10%) 16/210 (8%)
Febrile neutropenia 11/197 (6%) 9/210 (4%)
AdministraJon-‐related reacJons 93/197 (47%) 70/210 (33%)
Difference was mainly due to grade 1 injecJon site erythema (10% vs 0%) which was an-cipated following the change in route of administraJon.
NHL New Drugs
ü POLATUZOMAB VEDOTIN
ü SINE (SELINEXOR)
ü ABT-‐199
Polatuzomab Vedotin Preliminary Results of a Phase II Randomized Study (ROMULUS) of Polatuzumab VedoWn or
Polatuzumab VedoWn Plus Rituximab in PaWents with Relapsed/Refractory NHL Morschhauser F, et Al.
• ADC consisJng of the microtubule inhibitor MMAE conjugated to anJ-‐CD22 and CD79b monoclonal Ab via a protease-‐cleavable pepJde linker
• CD22 and CD79b are expressed by most B-‐cell hematologic malignancies
• Both ADCs have shown clinical acJvity in Phase I studies
TRIAL DESIGN
R + CD22 ADC
R + CD79b ADC
Randomize 1:1
PD
PD
Biopsy at Progression
R + CD79b ADC
R + CD22 ADC
ARM A
ARM B
Rituximab (R) (375 mg/m2) + ADC (2.4 mg/kg) administered in every-‐21-‐day cycles up to one year
• r/r FL = 41 • r/r DLBCL = 81
Archival Tumor Biopsy
TOXICITIES Neutropenia and peripheral neuropathy (above all sensiJve) are principal toxiciJes Neutropenia was most common g 3-‐4 treatment emergent adverse event Primarily laboratory abnormality with few clinically significant sequelae
Febrile neutropenia reported in 4% of all paJents Only one paJent disconJnued study treatment for neutropenia
Peripheral neuropathy was the most common AE leading to study treatment disconJnuaJon
RESPONSE ANALYSIS
DLBCL FL
R+CD22 ADC (N=42)
R+CD79b ADC (N=39)
R+CD22 ADC (N=21)
R+CD79b ADC (N=20)
ObjecWve response, n (%) Complete Response
ParJal Response
24 (57%) 10 (24%)
14 (33%)
22 (56%) 6 (15%)
16 (41%)
13 (62%) 2 (10%)
11 (52%)
14 (70%) 8 (40%)
6 (30%)
Stable disease, n (%) 3 (7%) 4 (10%) 6 (29%) 6 (30%)
Progressive disease, n (%) 7 (21%) 11 (30%) 1 (5%) 0
Unable to evaluate, n (%) 8 (19%) 2 (5%) 1 (5%) 0
Median DuraWon of Response, mo. (95% CI)
6.0 (2.9-‐12.2) NR (2.6-‐NR) 5.8 (2.6-‐10.1) NR (5.7-‐NR)
Polatuzomab Vedotin
NHL NEW DRUGS: Selinexor THE ORAL SELECTIVE INHIBITOR OF NUCLEAR EXPORT (SINE) SELINEXOR (KPT-‐330) ACTIVITY IN DOUBLE HIT DIFFUSE LARGE B CELL LYMPHOMAS (DLBCL) IN PRECLINICAL MODELS & CLINICAL
ACTIVITY IN PATIENTS WITH DLBCL J Kuruvilla, et Al.
Nuclear localizaJon and acJvaJon of mulJple TSP
ReducJon in levels of MYC, BCL2/BCL6 InhibiJon of NF-‐kB
Cancer cells can inacJvate their Tumor Suppressor Proteins (TSPs) via nuclear export
XPO1 is elevated in Non-‐Hodgkin’s Lymphoma (NHL), Chronic LymphocyJc Leukemia (CLL) and other malignancies
Selinexor (KPT-‐330) is a covalent, oral selecJve inhibitor of nuclear export (SINE) XPO1 :
• forces nuclear retenJon and acJvaJon of mul-ple TSPs • shows robust anJ-‐cancer acJvity in mulJple preclinical
models of NHL, largely independent of genotype • reduces proto-‐oncogene proteins including MYC, BCL2/
BCL6, BTK, Cyclin D and elevates IkB, leading to inhibiJon of NF-‐kB
SINE Reduce Growth of DLBCL in Vivo:
InducWon of p73 in p53mut DLBCL
Selinexor
Relapsed/Refractory B-‐Cell
MM/WM, NHL, CLL
Relapsed/Refractory B-‐Cell
MM/WM, DLBCL: (1) 35 mg/m2, (2) 60 mg/m2
Dose EscalaWon Cohorts Dose Expansion Cohorts
Arm 1
Characteristics N=51
Mean Age (Range) 60 years (23 – 79)
Mean Prior Treatment Regiments (Range) 4.1 (1–11)
Non Hodgkin's Lymphoma (NHL)
-Diffuse Large B-Cell (DLBCL) 25 Patients
-Follicular 7 Patients
-Mantle Cell 3 Patients
-Transformed 3 Patients
-Marginal Zone 1 Patient
-T Cell 5 Patients
Richter’s Transformation 7 Patients
Primary ObjecJve (modified 3+3 design): Safety, tolerability and Recommended Phase 2 Dose (RP2D) of KPT-‐330;
Selinexor dosing 10 doses/cycle (2-‐3 doses/week) or 8 doses/cycle (twice weekly) or 4 doses/cycle (once weekly) Doses 3 mg/m2 – 70 mg/m2 Major eligibility criteria: PaJents (ECOG ≤1) with relapsed/refractory hematologic tumors with no available standard treatments; No acJve CNS disease Documented progression at study entry ANC >1000/µL, Platelets >30,000/µL
NHL NEW DRUGS: ABT-199 Phase I Study of ABT-‐199 (GDC-‐0199) in PaWents with Relapsed/Refractory (R/R) non-‐Hodgkin
Lymphoma (NHL): Responses Observed in Diffuse Large B-‐Cell (DLBCL) and Follicular Lymphoma (FL) at Higher Cohort Doses.
Maohew S. Davids, et Al. • BCL-‐2 up-‐regolaJon is frequent in NHL pathogenesis and contributes to chemotherapy resistance
• BCL-‐2 antagonism promotes apoptosis in resistant tumor cells, important therapeuJc target • ABT-‐199 is a selecJve, potent, orally bioavailable, small molecule BCL-‐2 antagonist under invesJgaJon
for the treatment of paJents with NHL
ABT-‐199 Dosing Schema IniWal Ramp-‐Up Dosing of ABT-‐199 to Designated Cohort Dose (DCD)
StarJng doses ranging from 50 to 400 mg; Modified Fibonacci design; Single iniJal dose for PK on Day -‐7
Amended Ramp-‐Up Dosing for ABT-‐199
ABT-199: Safety CharacterisWc n (%) CharacterisWc n (%) Age years, median [range] 65 [25 – 85] Diagnosis MCL 20 (32) Bulky nodes ≥5 cm 27 (43) DLBCL 19 (31) Prior therapies Median [range] 3 [1 – 7] FL 14 (23) ≥3 44 (71) WM 4 (7) ≥5 16 (26) MZL 3 (5) Prior ASCT* 10 (16) MM 1 (2) LDH >Upper Normal 26 (42) PMBCL 1 (2)
DisconWnuaWons: 39 (63%) of paJents have disconJnued due to: • Progressive disease (n=32) • Enabled to Proceed to Transplant without prior disease progression (n=3) • AE (n=2; 1 rheumatoid arthriJs and 1 death in the se|ng of PD) • Withdrew consent (n=2)
Adverse Events
All Grades ≥20% of PaJents
N=62 n (%)
Nausea 23 (37)
Diarrhea 18 (29)
Anemia 14 (23)
FaJgue 14 (23)
Grade 3/4 ≥5% of PaJents
N=62 n (%)
Anemia 12 (19)
Neutropenia 6 (10)
Thrombocytopenia 4 (7)
Dose LimiWng ToxiciWes (DLTs) Two DLTs in Cohort 5 at 600 mg: • Grade 4 neutropenia • Grade 3 febrile neutropenia
Lymphoma Domande
1. Hodgkin: uso del Bretuximab VedoWn.
Posizonamento? Strategia del salvataggio?
2. Possibili nuove schedulee modi di
samministrazione del Rituximab?
3. Nuovi farmaci nei B cell lymphoma. Quali più
prometenW? Posizionamento futuro?
Acknowledgments
G. Benevolo
C. Boccomini
B. Botto
A. Castellino
C. Ciochetto
A. Chiappella
M. Nicolosi
L. Orsucci
P. Pregno
P. Riccomagno
Lymphoma Team Hematology Torino
FIL Secretary Alessandria
All FIL Centers
Biostatistics Torino
Trial Office Modena
![The Efficacy and Safety of a 1.6 mg/m2 Increase in a Bortezomib Regimenfile.scirp.org/pdf/OJBD_2015022715140986.pdf · regimen [1.6 mg/m2 2per month (BD 1.6 mg/m therapy)] was administered](https://img.pdfslide.us/doc/110x75/5ac1d3197f8b9ae45b8dcdcc/the-efficacy-and-safety-of-a-16-mgm2-increase-in-a-bortezomib-16-mgm2-2per.jpg)
