Phase II single-arm study of brentuximab vedotin in Chinese patients with relapsed/refractory classical Hodgkin lymphoma or systemic anaplastic large cell lymphoma

Figures & data

Figure 1. Mechanism of action of brentuximab vedotin. Reproduced with permission from Suri 12. © 2018 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc., on behalf of American Society for Clinical Pharmacology and Therapeutics.

Abbreviation: MMAE, monomethyl auristatin E

Table 1. Demographics and baseline disease characteristics (safety/mITT population)

Characteristics	cHL (n = 30)	sALCL (n = 9)	Total (N = 39)
Median age, years (range)	30 (21–64)	44 (20–61)	31 (20–64)
Male, n (%)	17 (57)	7 (78)	24 (62)
ECOG performance status, n (%) 0 1	18 (60) 12 (40)	3 (33) 6 (67)	21 (54) 18 (46)
Bone marrow involvement, n (%)	3 (10)	0	3 (8)
Extranodal involvement, n (%)	21 (70)	7 (78)	28 (72)
Any B symptoms, n (%)	2 (7)	2 (22)	4 (10)
Median time since initial diagnosis, years (range)	3.1 (1–13)	1.5 (0–9)	2.6 (0–13)
Ann Arbor stage, n (%) I II III IV	0 7 (23) 8 (27) 15 (50)	0 0 2 (22) 7 (78)	0 7 (18) 10 (26) 22 (56)
Prior BMT or SCT, n (%)	6 (20)	4 (44)	10 (26)
Prior radiotherapy, n (%)	14 (47)	3 (33)	17 (44)
Prior surgery, n (%)	2 (7)	0	2 (5)
Number of prior systemic therapies, n (%) 1 2 ≥3	5 (17) 5 (17) 20 (67)	5 (56) 1 (11) 3 (33)	10 (26) 6 (15) 23 (59)
Median number of prior systemic therapies, n (range)	3 (1–7)	1 (1–4)	3 (1–7)
Disease status relative to most recent prior therapy, n (%)^a Relapsed Refractory	12 (40) 9 (30)	4 (44) 3 (33)	16 (41) 12 (31)

^aRelapse was defined as a best response of complete or partial response to most recent prior therapy. Refractory was defined as a best response of stable disease or progressive disease to most recent prior therapy.

Abbreviations: BMT, bone marrow transplant; ECOG, Eastern Cooperative Oncology Group; cHL, classical Hodgkin lymphoma; mITT, modified intent to treat; sALCL, systemic anaplastic large cell lymphoma; SCT, stem cell transplant.

Table 2. Summary of best overall response (mITT population)

Best overall response, n (%) [95% CI]	cHL (n = 30)	sALCL (n = 9)	Total (N = 39)
ORR (CR + PR)	21 (70) [51–85]	6 (67) [30–93]	27 (69) [52–83]
CR	6 (20) [8–39]	5 (56) [21–86]	11 (28) [15–45]
PR	15 (50) [31–69]	1 (11) [0–48]	16 (41) [26–58]
DCR (CR + PR + SD)	29 (97) [83–100]	7 (78) [40–97]	36 (92) [79–98]
SD	8 (27) [12–46]	1 (11) [0–48]	9 (23) [11–39]
PD	1 (3) [0–17]	2 (22) [3–60]	3 (8) [2–21]

Abbreviations: CI, confidence interval; CR, complete response; DCR, disease control rate; cHL, classical Hodgkin lymphoma; mITT, modified intent to treat; ORR, overall response rate; PD, progressive disease; PR, partial response; sALCL, systemic anaplastic large cell lymphoma; SD, stable disease.

Figure 2. Swimmer plot of response to treatment from date of first dose by disease type (mITT population). (a) cHL and (b) sALCL.

Abbreviations: BOR, best overall response; CR, complete response; EOT, end of treatment; cHL, classical Hodgkin lymphoma; LTFU, long-term follow-up; mITT, modified intent to treat; PD, progressive disease; PR, partial response; sALCL, systemic anaplastic large cell lymphoma; SCT, stem cell transplant; SD, stable disease; sub anti-trt, subsequent antineoplastic therapy

Figure 3. Best percentage change in the sum of product diameters by disease type (mITT population; all patients). (a) cHL and (b) sALCL.

Abbreviations: CR, complete response; cHL, classical Hodgkin lymphoma; mITT, modified intent to treat; PD, progressive disease; PR, partial response; sALCL, systemic anaplastic large cell lymphoma; SD, stable disease; SPD, sum of product diameters

Figure 4. Kaplan–Meier curves for patients with cHL (left panels) and sALCL (right panels). Illustrating (a) and (b) duration of response (mITT population with CR or PR). (c) and (d) progression-free survival (mITT population). (e) and (f) overall survival (mITT population).

Abbreviations: CI, confidence interval; cHL, classical Hodgkin lymphoma; CR, complete response; mITT, modified intent to treat; NE, not estimable; ORR, overall response rate; sALCL, systemic anaplastic large cell lymphoma

Table 3. Summary of AEs (safety population)

Patients with ≥1 AE, n (%)	cHL (n = 30)	sALCL (n = 9)	Total (N = 39)
Any AE	30 (100)	9 (100)	39 (100)
Drug-related AE	30 (100)	8 (89)	38 (97)
Grade ≥3 AE	7 (23)	5 (56)	12 (31)
Drug-related Grade ≥3 AE	5 (17)	5 (56)	10 (26)
SAE	1 (3)	1 (11)	2 (5)
Drug-related SAE	1 (3)	0	1 (3)
AE resulting in study drug modification^a	3 (10)	1 (11)	4 (10)
AE resulting in study drug discontinuation	2 (7)	1 (11)	3 (8)
On-study death	0	0	0
Most frequent (≥20% overall) drug-related TEAEs (any grade)
ALT increased	18 (60)	6 (67)	24 (62)
Neutropenia (pooled^b)	19 (63)	5 (56)	24 (62)
AST increased	17 (57)	6 (67)	23 (59)
Leukopenia	15 (50)	2 (22)	17 (44)
Anemia	11 (37)	3 (33)	14 (36)
Peripheral sensory neuropathy	9 (30)	2 (22)	11 (28)
Reticulocyte count decreased	9 (30)	2 (22)	11 (28)
Diarrhea	8 (27)	2 (22)	10 (26)
Alopecia	8 (27)	1 (11)	9 (23)
Nausea	8 (27)	0	8 (21)
Any drug-related Grade ≥3 TEAE	5 (17)	5 (56)	10 (26)
Neutropenia (pooled^b)	4 (13)	3 (33)	7 (18)
Leukopenia	2 (7)	0	2 (5)
Lymphocyte count decreased	2 (7)	0	2 (5)
Blood phosphorus decreased	0	1 (11)	1 (3)
Lung infection	1 (3)	0	1 (3)
Urticaria	0	1 (11)	1 (3)

^aStudy drug modification is defined as a TEAE resulting in dose reduction, dose increased, dose delayed or drug (or dose) discontinued permanently. ^bIncludes preferred terms of neutropenia and neutrophil count decreased.

Abbreviations: AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; cHL, classical Hodgkin lymphoma; SAE, serious AE; sALCL, systemic anaplastic large cell lymphoma; TEAE, treatment-emergent AE.

Table 4. Summary of resolution and improvement of PN at EOT (safety population)

	cHL (n = 30)	sALCL (n = 9)	Total (N = 39)
Patients with treatment-emergent PN^a	14 (47)	6 (67)	20 (51)
Patients with resolution^b of PN	10 (71)	1 (17)	11 (55)
Patients with improvement^c in PN	0	0	0
Patients with no resolution or improvement in PN	4 (29)	5 (83)	9 (45)
Patients with ongoing^d PN
Grade 1	3 (21)	4 (67)	7 (35)
Grade 2	1 (7)	1 (17)	2 (10)
Grade ≥3	0	0	0

^aStandardized Medical Dictionary for Regulatory Activities query (Standardized MedDRA Queries) events. ^bResolution was defined as an event outcome of resolved or resolved with sequelae. ^cFor events that were not resolved, improved is defined as decreased by ≥1 grade from worst grade with no higher grade thereafter. Patients with improvement in any event were counted except for the case when all events are resolved. ^dOngoing was defined as event outcome of unresolved or unknown, or events without an end date.

Abbreviations: EOT, end of treatment; cHL, classical Hodgkin lymphoma; MedDRA, Medical Dictionary for Regulatory Activities; PN, peripheral neuropathy; sALCL, systemic anaplastic large cell lymphoma.

Suri A, Mould DR, Liu Y, et al. Population PK and exposure-response relationships for the antibody-drug conjugate brentuximab vedotin in CTCL patients in the Phase III ALCANZA study. Clin Pharmacol Ther. 2018;104(5):989–999.

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Data availability statement

The datasets, including the redacted study protocol, redacted statistical analysis plan, and individual participants’ data supporting the results reported in this article, will be made available within 3 months from initial request, to researchers who provide a methodologically sound proposal. The data will be provided after its de-identification, in compliance with applicable privacy laws, data protection, and requirements for consent and anonymization.