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