1. ALCANZA: Brentuximab Vedotin vs Methotrexate or Bexarotene in Patients With CD30-Positive Cutaneous T-Cell Lymphoma
New Findings in Hematology: Independent Conference Coverage of ASH 2016*; December 3-6, 2016; San Diego, California
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
This activity is supported by educational grants from Amgen, Celgene Corporation, Incyte, Merck, and Seattle Genetics.

2. ALCANZA: Background
CTCL: heterogeneous group of TCLs with skin involvement[1,2]
Generally chronic with quality of life affected by debilitating pruritus and skin infections
MF and pcALCL most common CD30+ CTCLs
Current treatments for advanced disease not associated with consistent long-term responses[3]
Brentuximab vedotin: anti-CD30 mAb conjugated to monomethyl auristatin E[4]
Phase II studies found clinical activity in MF and pcALCL with reasonable safety profile[4,5]
Current ALCANZA trial evaluated efficacy and safety of brentuximab vedotin vs methotrexate or bexarotene in treatment-experienced pts with CD30+ CTCL[6]
CTCL, cutaneous T-cell lymphoma; mAb, monoclonal antibody; MF, mycosis fungoides; pcALCL, primary cutaneous anaplastic large-cell lymphoma; TCL, T-cell lymphoma.
1. Swerdlow SH, et al. Blood. 2016;127: Rosen ST, et al. Hematology Am Soc Hematol Educ Program. 2006: Jawed SI, et al. J Am Acad Dermatol. 2014;70:223.e Duvic M, et al. J Clin Oncol. 2015;33: Kim YH, et al. J Clin Oncol. 2015;33: Kim YH, et al. ASH Abstract 182.
Slide credit: clinicaloptions.com

3. To maximum of sixteen 21-day cycles
ALCANZA: Study Design
Open-label, randomized, phase III trial[1]
Primary endpoint: ORR4 by independent review
Secondary endpoints
Rate of CR
PFS
Symptom burden/pt-reported outcomes (quality-of-life measurement with Skindex- 29[2])
Pts with CD30+ MF or pcALCL*; ≥ 1 prior systemic tx (MF) or prior radiotherapy or ≥ 1 prior system tx (pcALCL); no prior progression on both methotrexate and bexarotene (N = 131)
Posttreatment follow-up
Brentuximab vedotin
1.8 mg/kg IV Q3W
(n = 64)
Methotrexate
5-50 mg PO QW or
Bexarotene
300 mg/m2 PO daily
To maximum of sixteen 21-day cycles
MF, mycosis fungoides; ORR4, objective response rate with duration ≥ 4 months; pcALCL, primary cutaneous anaplastic large-cell lymphoma; tx, treatment
*Diagnosed by central review of ≥ 1 biopsy (2 for MF), where ≥ 10% neoplastic cells/lymphoid infiltrate CD30+.
1. Kim YH, et al. ASH Abstract 182.
2. Chren MM, et al. Arch Dermatol. 1997;133:
Slide credit: clinicaloptions.com

4. ALCANZA: Baseline Characteristics of Intent-to-Treat Population
Brentuximab Vedotin
(n = 64)
Methotrexate or Bexarotene
Median age, yrs (range)
62 (22-83)
59 (22-83)
Male, n (%)
33 (52)
37 (58)
ECOG PS 0-1, n (%)
61 (95)
62 (97)
Median average baseline CD30 expression, % (range)
33 (3-100)
31 (5-100)
MF,* n (%)
Early (IA-IIA)
Advanced (IIB-IVB)†
48 (75)
15 (31)
32 (67)
49 (77)
18 37)
30 (61)
pcALCL, n (%)
Skin only
Extracutaneous disease
16 (25)
9 (56)
7 (44)
15 (23)
11 (73)
4 (27)
Total prior therapies, median (range)
Prior systemic therapies
4.0 (0-13)
2.0 (0-11)
3.5 (1-15)
2.0 (1-8)
ECOG, Eastern Cooperative Oncology Group; MF, mycosis fungoides; pcALCL, primary cutaneous anaplastic large-cell lymphoma; PS, performance status.
*1 pt per arm excluded because of incomplete staging data. †Stage IVB MF only in brentuximab arm (n = 7).
Slide credit: clinicaloptions.com
Kim YH, et al. ASH Abstract 182.

5. ALCANZA: ORR4, PFS, CR, and Change in Symptom Burden
Endpoint
Brentuximab Vedotin (n = 64)
Methotrexate or Bexarotene (n = 64)
Difference (95% CI)
P Value
ORR4, n (%)
36 (56.3)
8 (12.5)
43.8 (29.1 to 58.4)
< .0001
CR, n (%)
10 (15.6)
1 (1.6)
14.1 (-4.0 to 31.5)
.0046*
Median PFS, mos
16.7
3.5 --
< .0001*†
Mean max. reduction in Skindex-29 symptom domain, points
-27.96
-8.62
(-26.6 to -11.2)
< .0001*
*Adjusted P value from weighted Holm’s procedure. †HR: (95% CI: ).
ECOG, Eastern Cooperative Oncology Group; MF, mycosis fungoides; ORR4, objective response rate with duration ≥ 4 months; pcALCL, primary cutaneous anaplastic large-cell lymphoma; PS, performance status.
PFS significantly improved for subgroups defined by pt characteristics (baseline ECOG PS of 0, sex, age < 65 yrs, geographical region), disease characteristics (MF and pcALCL, skin involvement, baseline skin tumor score), and treatment (bexarotene and methotrexate)
Slide credit: clinicaloptions.com
Kim YH, et al. ASH Abstract 182.

6. ALCANZA: ORR4 by Disease Type and Stage
Pt Group
Brentuximab Vedotin
Bexarotene or Methotrexate
Total, n (%) (N = 64)
ORR4, %
ORR, %
CR, %
Total, n (%) (N = 64)
ITT
64 (100) 56 67 16 13 20 2 MF
48 (75) 50 65 10
49 (77)
Stage
IA-IIA II
IIIA-IIIB
IVA
IVB
15 (31)
19 (40)
4 (8)
2 (4)
7 (15) 40 63
100 29 53 68 75 57 7
18 (37)
19 (39)
9 (18) 22 5 NA 28
pcALCL
16 (25) 31
15 (23) 33
Disease involvement
Skin only
Extracutaneous disease
9 (56)
7 (44) 89 44 14
11 (73)
4 (27) 27 45 9
ITT, intent to treat; NA, not applicable; ORR4, objective response rate with duration ≥ 4 months; pcALCL, primary cutaneous anaplastic large-cell lymphoma.
Slide credit: clinicaloptions.com
Kim YH, et al. ASH Abstract 182.

7. ALCANZA: ORR4 by Key Demographic Subgroups
Pt Group, n/n (%)
Brentuximab Vedotin
Methotrexate or Bexarotene
Difference (95% CI)
Overall
36/64 (56.3)
8/64 (12.5)
43.8 (29.1 to 58.4)
Baseline ECOG PS
≥ 1
29/43 (67.4)
7/21 (33.3)
6/46 (13.0)
2/18 (11.1)
54.4 (37.3 to 71.5)
22.2 (-10.2 to 51.2)
Sex
Male
Female
19/33 (57.6)
17/31 (54.8)
5/37 (13.5)
3/27 (11.1)
44.1 (21.3 to 63.3)
43.7 (18.5 to 64.7)
Age
< 65 yrs
≥ 65 yrs
20/36 (55.6)
16/28 (57.1)
2/40 (5.0)
6/24 (25.0)
50.6 (29.3 to 68.3)
32.1 (6.9 to 57.4)
Region
Europe
Non-Europe
23/37 (62.2)
13/27 (48.1)
3/35 (8.6)
5/29 (17.2)
53.6 (32.7 to 71.3)
30.9 (4.2 to 53.5)
ECOG, Eastern Cooperative Oncology Group; ORR4, objective response rate with duration ≥ 4 months; PS, performance status.
Slide credit: clinicaloptions.com
Kim YH, et al. ASH Abstract 182.

8. ALCANZA: ORR4 by Key Disease and Treatment Subgroups
Pt Group, n/n (%)
Brentuximab Vedotin
Methotrexate or Bexarotene
Difference (95% CI)
Overall
36/64 (56.3)
8/64 (12.5)
43.8 (29.1 to 58.4)
Disease MF
pcALCL
24/48 (50.0)
12/16 (75.0)
5/49 (10.2)
3/15 (20.0)
39.8 (19.9 to 56.2)
55.0 (19.7 to 80.4)
Treatment
Bexarotene
Methotrexate
6/38 (15.8)
2/26 (7.7)
40.5 (23.7 to 57.3)
48.6 (26.7 to 67.7)
Skin involvement
Skin only
Skin and extracutaneous
21/31 (67.7)
15/33 (45.5)
5/30 (16.7)
3/34 (8.8)
51.1 (27.3 to 71.0)
36.6 (12.3 to 56.3)
Baseline skin tumor score
> 0
26/41 (63.4)
10/23 (43.5)
2/38 (5.3)
6/26 (23.1)
58.2 (38.1 to 74.1)
20.4 (-5.5 to 46.3)
MF, mycosis fungoides; ORR4, objective response rate with duration ≥ 4 months; pcALCL, primary cutaneous anaplastic large-cell lymphoma.
Slide credit: clinicaloptions.com
Kim YH, et al. ASH Abstract 182.

9. ALCANZA: Safety and Tolerability
4 deaths in brentuximab arm during study period
3 deemed unrelated to study drug (1 each: lymphoma progression, pulmonary embolism, sepsis)
1 pt with T3bN0M1 pcALCL died due to multiple organ dysfunction related to tumor necrosis at visceral disease sites attributed to brentuximab vedotin
AE, n (%)
Brentuximab Vedotin
(n = 66)
Methotrexate or
Bexarotene
(n = 62)
Any AE
63 (95)
56 (90)
Grade ≥ 3 AE
27 (41)
29 (47)
Serious AE
19 (29)
18 (29)
AE-related drug discontinuation*
16 (24)
5 (8)
Death ≤ 30 days of last study drug dose
4 (6)
Death ≤ median 23 mos of follow-up
14 (23)
AE, adverse event; pcALCL, primary cutaneous anaplastic large-cell lymphoma.
*Brentuximab arm: peripheral neuropathy, n = 9; skin hypersensitivity, n = 3; E coli infection, n = 1; impetigo, n = 1; pulmonary embolism, n = 1; urticaria, n = 1; vertigo, n = 1. Methotrexate or bexarotene arm: maculopapular rash, n = 1; asthenia, n = 1; hematuria, n = 1; hypernatremia, n = 1; neutropenia, n = 1; periorbital infection, n = 1; somnolence, n = 1.
Slide credit: clinicaloptions.com
Kim YH, et al. ASH Abstract 182.

10. ALCANZA: Common Treatment-Emergent AEs
Treatment-Emergent AEs Reported in ≥ 15% of Pts,* %
Brentuximab Vedotin
Methotrexate or
Bexarotene
Peripheral neuropathy 67 6
Nausea 36 13
Diarrhea 29
Fatigue 27
Vomiting 17 5
Alopecia 15 3
Pruritus
Pyrexia 18
Decreased appetite
Hypertriglyceridemia 2
18†
AE, adverse event.
*Drug exposure: median 12 cycles (36 wks) of brentuximab vedotin vs 17 wks of bexarotene or 9 wks of methotrexate.
†30% of pts receiving bexarotene experienced elevated triglycerides.
Slide credit: clinicaloptions.com
Kim YH, et al. ASH Abstract 182.

11. ALCANZA: Conclusions
Brentuximab vedotin showed significantly longer ORR4 vs methotrexate/bexarotene in pts with CD30+ MF and pcALCL (56.3% vs 12.5%, respectively; P < .0001)
Significantly higher rates observed with brentuximab vedotin vs methotrexate/bexarotene for ORR, CR, PFS, and life quality symptom burden
Brentuximab vedotin safety profile consistent with previous reports
Investigators suggest that brentuximab vedotin may be valuable in managing pts with CD30+ CTCL requiring systemic treatment
CTCL, cutaneous T-cell lymphoma; MF, mycosis fungoides; ORR4, objective response rate with duration ≥ 4 months; pcALCL, primary cutaneous anaplastic large-cell lymphoma.
Slide credit: clinicaloptions.com
Kim YH, et al. ASH Abstract 182.

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