2016 ASCO Annual Meeting
Non-Hodgkin’s LymphomaMyelomaAuto HSCT
CK DAS, AIIMS, NEW DELHI, INDIA
CASTOR: Study Design
Primary endpoint: PFS Secondary endpoints: TTP, OS, ORR, VGPR, CR, MRD, time to response; DoR
Pts with relapsed/refractory MM who received ≥ 1 prior
regimen including bortezomib (but not
refractory to bortezomib)(N = 498)
Daratumumab 16 mg/kgCycles 1-3 Q7D, 4-8 Q21D, 9+ Q28D
+ VD(n = 251)
VD(n = 247)
Median follow-up: 7.4 mos
Phase III study
CASTOR: Baseline Characteristics
Characteristic DVd(n = 251)
Vd(n = 247)
Median age, yrs (range) 64 (30-88) 64 (33-85)
ISS stage, % I II III
393824
394121
Median time from diagnosis, yrs (range) 3.87 (0.7-20.7) 3.72 (0.6-18.6)
Prior lines of therapy, % 1 2 ≥ 3
492824
463024
Prior ASCT, % 62 60Prior PI, % 67 70
Prior IMiD, % 71 80Refractory to last line of therapy, % 30 34
CASTOR: PFS in Total Study PopulationPF
S (%
)
0
0.2
0.4
0.6
0.81.0
0 3 6 9 12
15Mos
1 yr PFS*
60.7%
26.9%
DVdVd
Median (mos)
NR7.2HR: 0.39 (95% CI: 0.28-0.53; P < .0001)
CASTOR: Other Efficacy Outcomes
Efficacy Outcome DVd(n = 251)
Vd(n = 247)
HR (95% CI) P Value
Median PFS following 1 prior treatment, mos 1-yr PFS, %
NR77.5
7.529.4
0.31 (0.18-0.52) < .0001
Median TTP, mos 1-yr PFS, %
NR65.4
7.328.8
0.30 (0.21-0.43) < .0001
ORR, % ≥ VGPR ≥ CR
835919
63299
< .0001< .0001.0012
MRD negative, % 14 3
Time to PR occurred early in pts (~2 mos), but CR took longer to develop in many pts (≥ 8 mos)
Multiple myeloma- ASCT upfront
Phase III EMN02/HO95 MM Trial (Abs-8000)
EMN02/HO95 MM: prospective, randomized phase III trial evaluating upfront ASCT vs VMP for newly diagnosed MM
Comparisons included: upfront ASCT vs novel agent-based therapies; single vs double ASCT; consolidation vs no consolidation therapy safety and toxicity; quality of life
Phase III EMN02/HO95 MM Trial
Adult pts 18 - 65 yrs
with symptomati
c, newly diagnosed
MM(N = 1192)
Induction: VCD* x 3-4 21-day
cycles
CTX 2-4 g/m2
+ G-CSF
+ PBSC
collection
VMP x 4, 42-day cycles:
(n = 497)
HDM x 1-2 courses:M: 100 mg/m2
+ Single (n = 488) or
double (n = 207) ASCT(n = 695)
Ran
dom
izat
ion
1
Ran
dom
izat
ion
2
Primary endpoint: PFS from R1 and R2 Secondary endpoints: response, OS from R1 and R2, toxicity, QoL
Lenalidomide
10 mg daily Days 1-21/28
VRD† x 2,28-day cycles
consolidation therapy
No consolidat
ion therapy
EMN02/HO95 MM Trial: Pt Population
Characteristic VMP(n = 497)
ASCT(n = 695)
Median age, yrs (IQR) 58 (52-63) 58 (53-62)
Male,% 56 59
ISS stage/revised ISS stage, % I II III
41/1938/6421/17
41/1639/6720/17
FISH analysis, %* Standard risk High risk
54.945.1
49.850.2
*Evaluable pts: VMP, n = 401; ASCT, n = 582.
EMN02/HO95 MM Trial: Efficacy
Median follow-up: 26 mos (range: 19-37 mos)
Outcome VMP ASCT HR (95% CI; P Value)
PFSOverall population, n Median, mos 3 yr, %
49744
57.5
695NR66.1
0.73 (0.59-0.90; .003)
Standard-risk cytogenetics, n Median, mos 3 yr, %
22046
69.6
290NR76.6
0.68 (0.47-0.98;.034)
High-risk cytogenetics, n Median, mos 3 yr, %
18132
43.2
29242
55.20.69 (0.52-0.92;
.010)
Response (n = 451) (n = 641) -- VGPR or better, % 73.8 85.5 < .001
Lenalidomide Maintenance After ASCT- Meta analysis
Abs-8001
Prospectively planned meta-analysis of 3 studies
Inclusion criteria Lenalidomide maintenance vs control
(placebo or no maintenance) after ASCT Database lock for primary efficacy analysis
3 studies fulfilled criteria
Lenalidomide maintenance intended to be given until progressionIFM elected to discontinue lenalidomide in 2010 due to second primary
malignancy signal, whereas the NCI and GIMEMA chose to continue until progression
Lenalidomide Maintenance After ASCT in MM: Meta-analysis
Study Treatment Arms Pts, n
CALGB 100104 Lenalidomide maintenancePlacebo
231229
IFM 2005-02 Lenalidomide maintenancePlacebo
307307
GIMEMA(RV-MM-PI-209)
Lenalidomide maintenanceNo maintenance
6768
Lenalidomide Maintenance After ASCT in MM: Pooled Patient Characteristics
Characteristic Lenalidomide(n = 605)
Control(n = 604)
Median age, yrs 58 5860 yrs of age or older, % 39 38
ISS stage at diagnosis, % I II III
373119
452815
CR/VGPR after ASCT, % 53 56Prior lenalidomide induction, % 24 24Adverse risk cytogenetics,* % 15 10
*t(4;14) or del(17p); from IFM and GIMEMA studies only.
Lenalidomide Maintenance After ASCT in MM: Overall Survival
Lenalidomide maintenance significantly improved survival after ASCT from pooled data analysis 7-yr OS: 62% vs 50% in the control arm
Median OS: not estimable vs 86.0 mos in control arm (median follow-up: 80 mos) Overall HR: 0.74 (95% CI: 0.62-0.89; P = .001)
All studies showed lenalidomide benefit, but results were heterogeneous (P = .047) CALGB HR: 0.56 (95% CI: 0.42-0.76) IFM HR: 0.91 (95% CI: 0.72-1.15) GIMEMA HR: 0.66 (95% CI: 0.34-1.26)
Lenalidomide Maintenance After ASCT in MM: Other Outcomes
Lenalidomide maintenance benefit seen in most subgroups except high-risk cytogenetics HR: 1.18 (95% CI: 0.66-2.10)
Mean duration of maintenance treatment: 25 mos in IFM trial, 30 mos in CALGB trial
Incidence of second primary malignancies significantly higher with lenalidomide maintenance Hematologic: HR: 2.03 (95% CI: 1.14-3.61; P = .015) Solid tumor: HR: 1.71 (95% CI: 1.04-2.79; P = .032)
KEYNOTE-023: Pembrolizumab + Rd in R/R MM
Treatment doses tested– Pembrolizumab: 2 mg/kg or 200 mg IV Q2W– Lenalidomide: 10 or 25 mg – Dexamethasone: 40 mg
Final MTD: pembrolizumab 200 mg IV Q2W + lenalidomide 25 mg + dexamethasone 40 mg
Primary endpoints: safety, tolerability
Secondary endpoints: ORR, DoR, PFS, OS
Median pt follow-up: 9 mos
KEYNOTE-023: Baseline Characteristics
CharacteristicsPembrolizumab + Lenalidomide +
Dexamethasone(N = 51)
Median age, yrs (range) 61 (46-77)Male, % 65ECOG PS 0 / 1, % 22/77LDH ≤ 400 IU/mL, % 57β-2 microglobulin < 3.5 mg/L, % 65
Median prior therapies (range)≥ 5 prior lines, %
4 (1-10)39
Prior ASCT, % 86Refractory to lenalidomide, % 75Refractory to bortezomib, % 63Refractory to last line of therapy, %Refractory to lenalidomide as last line, %
7820
KEYNOTE-023: Response Rates
88% of pts showed some decrease in M protein or free light chains from baseline
Best Overall Response, %Efficacy
Population(n = 40)
Len-Refractory Population
(n = 29)ORR Stringent CR VGPR PR
503
1335
383
1024
SD 48 59
Disease control rate (CR + PR + SD) 98 97
PD 3 3
Non Hodgkin Lymphoma
Two years rituximab maintenance vs. observation after B-R in MCL -A subgroup study of the StiL NHL7-2008 MAINTAIN trial).
Abs-7503 Effect of rituximab maintenance vs observation after first-line
treatment with B-R in patients with previously untreated MCL.
Pts with stage II (with bulky disease > 7 cm), III, or IV disease Primary endpoint was progression free survival (PFS) Secondary endpoints included response rates, overall survival
(OS), time to progression, event free survival, toxicity. Patients were treated with up to 6 cycles of B-R plus 2
additional rituximab cycles. 120 Patients who have responded to B-R were then randomized to either rituximab maintenance (375 mg/m2every 2 months for a total of 2 years) or observation only.
MAINTAIN trial- results
120 patients were evaluable for the analysis,
59 (49%) -Maintenance with rituximab and 61 (51%)- observation
Median time of observation was 54.2 months
No significant difference in PFS between both arms (p = 0.130, 47 events, HR 0.64, 95% CI 0.36 – 1.14).
Median PFS for R maintenance-Not reached vs. Observation arm - 54.7 mos (95% CI 40.1. – n. y. r.)
The results for overall survival showed no difference (p = 0.271, 27 events, HR 1.53, 95% CI 0.73 – 3.32)
Longer follow-up is needed before final results can be presented
Effect of bortezomib +BR on complete remission (CR) in previously untreated high-risk (HR) follicular lymphoma (FL):
Phase II trial of the ECOG-ACRIN Cancer Research Group (E2408).
Abs-7507
E2408 tested
Whether bortezomib (V) improves the CR rate when added to standard BR induction in untreated HR FL
Whether lenalidomide (len) improves remission duration when added to maintenance rituximab (MR).
Pts with untreated HR grade I/II or IIIa FL.
HR was defined as high tumor burden by GELF and/or FLIPI 3-5.
High risk unreated FL
N=250Arm B-
BVR x 6 then MR x 2 yrs
Arm C-BR x 6 then MR x 2 yrs + len 20 mg/day x 1 yr
Median follow-up: 16 mos
1:2:2 randomisation
Arm A- BR x 6 followed by MR x 2 years
E2408- Results
This analysis reports on the first primary objective of CR rate with induction therapy (Tx) with arms A) + C)
Analyses are based on 222 pts (BVR n = 85 vs BR n = 137
ORR- BVR was 91% vs 90% for BR
CR rates were 74% vs 58%, (2-sided P= 0.016).
Sandwich-like GDP chemotherapy with RT in newly diagnosed, stage IE to IIE, upper aerodigestive tract NK/T lymphoma.
Abs-7561
Sandwich protocol-Earlier IFRT after an initial 2 cycles of GDP, followed by further "consolidation" 2 to 4 cycles
Newly diagnosed stage IE/IIE ENKTL, having fever and/or extensive lesions were enrolled.
Primary endpoints were objective response rate (ORR) and complete remission (CR) rate after initial chemotherapy and whole treatment.
Secondary endpoints were 2-year OS, PFS and toxicity.
GDP+RT- results
Seventy-two patients completed treatment
After initial 2 cyles ORR- 91.7% (CR-22 (30.6%), PR- 44 patients (61.1%))
After whole treatment completion, CR rate was 81.9% (59/72) and ORR was 91.7% (66/72).
Median follow-up of 22 months 2-year OS - 84.6% (95%CI, 80.3% to 88.9%) 2-year PFS - 81.6% (95%CI, 76.6% to 86.6%).
Thank You