TO THE EDITOR:

Relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) are associated with poor survival outcomes1-3; therefore, there is a need for novel treatment strategies. Overexpression of programmed death ligand-1 (PD-L1) and CD30 are observed in a proportion of PTCL (15%-41%4 and 46%-100%5) and CTCL (27%-73%4 and 47%-76%6,7) cases, thus representing potential therapeutic targets. Nivolumab is a fully human immunoglobulin G4 monoclonal antibody that inhibits programmed death-1 (PD-1)/PD-L1 binding,8 whereas brentuximab vedotin (BV) is an anti-CD30 antibody–drug conjugate.9 Limited studies have demonstrated modest activity of PD-1 inhibitor therapy in CTCL10; however, activity is more variable in PTCL.11 BV was approved in CTCL based on improved efficacy in the phase 3 ALCANZA study; however, some responses were not durable.12 Therefore, combining PD-1 inhibitors with BV may improve efficacy in patients with PTCL and CTCL. In the current analysis, we evaluated the efficacy and safety of nivolumab plus BV (NBV) in the PTCL and CTCL cohorts of the phase 2 CheckMate 436 (NCT02581631) study.

As previously described,13,14 CheckMate 436 enrolled patients aged ≥18 years with R/R PTCL (excluding anaplastic large-cell lymphoma) or CTCL (mycosis fungoides [MF]/Sézary syndrome [SS] subtypes) who had received ≥1 prior line of therapy, had an Eastern Cooperative Oncology Group performance status of 0-1, and CD30 expression of ≥1% in the tumor or tumor-infiltrating lymphocytes (TILs; determined by immunohistochemistry at a local laboratory). Patients received nivolumab 240 mg (day 8 of cycle 1; day 1 of each subsequent 3-week cycle) plus BV 1.8 mg/kg intravenously (day 1 of all cycles) until progressive disease (PD) or unacceptable toxicity. Primary end points were investigator-assessed overall response rate (ORR) assessed by fludeoxyglucose positron emission tomography-computed tomography, or computed tomography/magnetic resonance imaging (PTCL, per Lugano classification 201415; CTCL, assessed by Global Response Score per consensus statement of the International Society for Cutaneous Lymphoma)16 and safety. Secondary end points included duration of response (DOR), complete response (CR), duration of CR, progression-free survival (PFS) by investigator, and overall survival. This study was conducted in accordance with the International Conference on Harmonization Good Clinical Practice guidelines and the Declaration of Helsinki; institutional review board approval was obtained. All patients provided written informed consent.

Overall, 34 and 30 patients with PTCL and CTCL were enrolled, of whom 33 and 29 received treatment, respectively; 2 patients did not receive treatment due to PD and laboratory results out of range for inclusion. In violation of eligibility criteria, 1 patient who did not receive any prior lines of therapy was recruited to the CTCL cohort. Median (range) age was 60 (38-80) and 61 (37-77) years in PTCL and CTCL cohorts, respectively; a larger proportion of patients were male (PTCL: n = 22 of 33 [66.7%]; CTCL: n = 16 of 29 [55.2%]; supplemental Table 1). At study entry, 54.5% (n = 18 of 33) of patients with PTCL had PTCL–not otherwise specified, 30.3% (n = 10 of 33) had angioimmunoblastic T-cell lymphoma, and 15.2% (n = 5 of 33) had an unknown PTCL subtype; 82.8% (n = 24 of 29) and 17.2% (n = 5 of 29) of patients with CTCL had MF and SS subtypes, respectively. Overall, 51.5% (PTCL) and 31.0% (CTCL) of patients had stage IV disease. In the PTCL and CTCL cohorts, 78.8% (n = 26 of 33) and 96.6% (n = 28 of 29) of patients had baseline PD-L1 expression of ≥1%, respectively; 93.3% (n = 28 of 30) and 96.4% (n = 27 of 28) of evaluable patients had tumor CD30 expression ≥1% or TILs, respectively. All patients had CD30 expression ≥1% at local screening; however, 2 patients had CD30 expression <1% per Bristol Myers Squibb central biomarker assessment. In the PTCL cohort, median (range) PD-L1 and CD30 expression were 60.0% (0.0-100.0) and 35.0% (0.0-100.0), respectively; in the CTCL cohort, this was 50.0% (0.0-95.0) and 27.5% (0.0-95.0). Patients with PTCL and CTCL received a median (range) of 2 (1-5) and 3 (0-6) prior lines of systemic therapy, respectively. Patients received a median (range) of 5 (1-35) doses of nivolumab and BV in the PTCL cohort and 6 (1-73) and 7 (1-42) doses, respectively, in the CTCL cohort. At database lock (30 March 2022), all patients discontinued treatment, most commonly due to PD (PTCL, 57.6% [n = 19 of 33]; CTCL, 44.8% [n = 13 of 29]).

At a median (range) follow-up (defined as time from first dose to last known date alive or death) of 9.6 (0.7-52.1) and 24.4 (0.6-61.0) months in patients with PTCL and CTCL, respectively, the ORR (95% confidence interval [CI]) was 45.5% (28.1-63.6) and 41.4% (23.5-61.1); 33.3% (n = 11 of 33) and 3.4% (n = 1 of 29) of patients achieved a CR (Table 1). In patients with PTCL, median DOR was 4.6 (95% CI, 2.8-12.8) months (supplemental Figure 1) and median PFS was 4.3 (95% CI, 1.6-5.6) months (supplemental Figure 2); these were 27.0 (95% CI, 2.8-not reached [NR]; supplemental Figure 1) and 15.6 (95% CI, 4.9-NR; supplemental Figure 2) months for the CTCL cohort, respectively. Median overall survival (95% CI) was 11.1 (5.2-15.3) and 37.2 (18.6-NR) months for PTCL and CTCL, respectively.

Table 1.

Efficacy results (ORR, DOR, PFS, OS)

EfficacyPTCL (n = 33)CTCL (n = 29)
ORR, n (%) 15 (45.5) 12 (41.4) 
80% CI, % 33.3-58.0 28.8-55.0 
95% CI, % 28.1-63.6 23.5-61.1 
Best overall response, n (%)   
CR 11 (33.3)  1 (3.4) 
PR 4 (12.1)  11 (37.9) 
SD 6 (18.2) 11 (37.9)§  
PD 10 (30.3) 1 (3.4) 
Unable to determine 2 (6.1) 5 (17.2) 
TTR, median (range), mo 1.4 (1.1-5.5) NR (0.7-10.1) 
TTCR, median (range), mo 2.6 (1.1-7.6) 4.8 (4.8-4.8) 
DOR, median (95% CI), mo 4.6 (2.8-12.8) 27.0 (2.8-NR) 
DOCR, median (95% CI), mo 7.4 (2.2-NR) NR 
PFS, median (95% CI), mo 4.3 (1.6-5.6) 15.6 (4.9-NR) 
PFS rate at 12 mo, % (95% CI) 13.8 (2.9-33.0) 67.6 (43.3-83.3) 
PFS rate at 24 mo, % (95% CI) 6.9 (0.5-25.6) 46.4 (18.3-70.7) 
OS, median (95% CI), mo 11.1 (5.2-15.3) 37.2 (18.6-NR) 
OS rate at 12 mo, % (95% CI) 45.1 (27.7-61.0) 78.9 (58.9-89.9) 
OS rate at 24 mo, % (95% CI) 25.8 (12.3-41.6) 62.9 (41.7-78.1) 
EfficacyPTCL (n = 33)CTCL (n = 29)
ORR, n (%) 15 (45.5) 12 (41.4) 
80% CI, % 33.3-58.0 28.8-55.0 
95% CI, % 28.1-63.6 23.5-61.1 
Best overall response, n (%)   
CR 11 (33.3)  1 (3.4) 
PR 4 (12.1)  11 (37.9) 
SD 6 (18.2) 11 (37.9)§  
PD 10 (30.3) 1 (3.4) 
Unable to determine 2 (6.1) 5 (17.2) 
TTR, median (range), mo 1.4 (1.1-5.5) NR (0.7-10.1) 
TTCR, median (range), mo 2.6 (1.1-7.6) 4.8 (4.8-4.8) 
DOR, median (95% CI), mo 4.6 (2.8-12.8) 27.0 (2.8-NR) 
DOCR, median (95% CI), mo 7.4 (2.2-NR) NR 
PFS, median (95% CI), mo 4.3 (1.6-5.6) 15.6 (4.9-NR) 
PFS rate at 12 mo, % (95% CI) 13.8 (2.9-33.0) 67.6 (43.3-83.3) 
PFS rate at 24 mo, % (95% CI) 6.9 (0.5-25.6) 46.4 (18.3-70.7) 
OS, median (95% CI), mo 11.1 (5.2-15.3) 37.2 (18.6-NR) 
OS rate at 12 mo, % (95% CI) 45.1 (27.7-61.0) 78.9 (58.9-89.9) 
OS rate at 24 mo, % (95% CI) 25.8 (12.3-41.6) 62.9 (41.7-78.1) 

DOCR, duration of CR; OS, overall survival; PR, partial response; SD, stable disease; TTCR, time to CR; TTR, time to response.

CIs based on the Clopper-Pearson method.

Based on Lugano Classification 2014.15 

There were 3 patients with baseline PD-L1 < 1% in the PTCL cohort; 2 achieved a CR and 1 a PR.

§

There was 1 patient with baseline PD-L1 < 1% in the CTCL cohort; this patient achieved SD.

Median and rates calculated using Kaplan-Meier method.

In the PTCL cohort, 84.8% (n = 28 of 33) of patients experienced any-grade treatment-related adverse events (TRAEs); most commonly fatigue (24.2%, n = 8 of 33, Table 2). Grade 3/4 TRAEs were reported in 45.5% (n = 15 of 33) of patients, most commonly neutropenia (15.2%, n = 5 of 33); 1 patient experienced grade 5 treatment–related pneumonitis (no prior chest radiation therapy; treated with levafloxacin, steroids, and mycophenolate mofetil). Any-grade treatment-emergent adverse events (TEAEs) occurred in 100% (n = 33 of 33) of patients, and grade 3/4 TEAEs occurred in 66.6% (n = 22 of 33; supplemental Table 2). In the CTCL cohort, 89.7% (n = 26 of 29) of patients experienced any-grade TRAEs; the most common was peripheral neuropathy (27.6%, n = 8 of 29; Table 2). Grade 3/4 TRAEs occurred in 44.8% (n = 13 of 29) of patients, of which 13.8% (n = 4 of 29) were skin-related; no grade 5 TRAEs were reported. Any-grade TEAEs occurred in 100% (n = 29 of 29) of patients, and grade 3/4 TEAEs occurred in 58.6% (n = 17 of 29; supplemental Table 2). Overall, 78.8% (26 of 33) and 48.3% (14 of 29) of patients died in the PTCL and CTCL cohorts, respectively, most commonly due to PD (63.6%, n = 21 of 33; 37.9%, n = 11 of 29; Table 2). One death was treatment-related in the PTCL cohort (grade 5 pneumonitis); none were treatment-related in the CTCL cohort.

Table 2.

Safety data in patients with R/R PTCL and CTCL

TRAEs in ≥5% of patients, n (%)PTCL (n = 33)CTCL (n = 29)
Any gradeGrade 3/4Any gradeGrade 3/4
All TRAEs 28 (84.8) 15 (45.5) 26 (89.7) 13 (44.8) 
Fatigue 8 (24.2) 2 (6.1) 4 (13.8) 
Nausea 6 (18.2) 6 (20.7) 
Pyrexia 6 (18.2) 5 (17.2) 
Neutropenia 5 (15.2) 5 (15.2) 
Peripheral neuropathy 5 (15.2) 1 (3.0) 8 (27.6) 
Diarrhea 5 (15.2) 1 (3.0) 6 (20.7) 1 (3.4) 
Anemia 5 (15.2) 1 (3.0) 1 (3.4) 
Increased aspartate aminotransferase 5 (15.2) 3 (10.3) 1 (3.4) 
Paresthesia 5 (15.2) 1 (3.4) 
Thrombocytopenia 4 (12.1) 2 (6.1) 1 (3.4) 1 (3.4) 
Peripheral sensory neuropathy 4 (12.1) 1 (3.0) 2 (6.9) 
Infusion-related reaction 4 (12.1) 6 (20.7) 1 (3.4) 
Pruritis 4 (12.1) 2 (6.9) 
Arthralgia 4 (12.1) 1 (3.4) 
Rash 3 (9.1) 4 (13.8) 2 (6.9) 
Increased alanine aminotransferase 2 (6.1) 2 (6.9) 
Pneumonitis  2 (6.1) 1 (3.4)  1 (3.4)  
Increased blood alkaline phosphatase 2 (6.1) 
Rash maculo-papular 1 (3.0) 2 (6.9) 1 (3.4) 
Dermatitis exfoliative generalized 4 (13.8) 2 (6.9) 
Rash macular 2 (6.9) 
TRAEs in ≥5% of patients, n (%)PTCL (n = 33)CTCL (n = 29)
Any gradeGrade 3/4Any gradeGrade 3/4
All TRAEs 28 (84.8) 15 (45.5) 26 (89.7) 13 (44.8) 
Fatigue 8 (24.2) 2 (6.1) 4 (13.8) 
Nausea 6 (18.2) 6 (20.7) 
Pyrexia 6 (18.2) 5 (17.2) 
Neutropenia 5 (15.2) 5 (15.2) 
Peripheral neuropathy 5 (15.2) 1 (3.0) 8 (27.6) 
Diarrhea 5 (15.2) 1 (3.0) 6 (20.7) 1 (3.4) 
Anemia 5 (15.2) 1 (3.0) 1 (3.4) 
Increased aspartate aminotransferase 5 (15.2) 3 (10.3) 1 (3.4) 
Paresthesia 5 (15.2) 1 (3.4) 
Thrombocytopenia 4 (12.1) 2 (6.1) 1 (3.4) 1 (3.4) 
Peripheral sensory neuropathy 4 (12.1) 1 (3.0) 2 (6.9) 
Infusion-related reaction 4 (12.1) 6 (20.7) 1 (3.4) 
Pruritis 4 (12.1) 2 (6.9) 
Arthralgia 4 (12.1) 1 (3.4) 
Rash 3 (9.1) 4 (13.8) 2 (6.9) 
Increased alanine aminotransferase 2 (6.1) 2 (6.9) 
Pneumonitis  2 (6.1) 1 (3.4)  1 (3.4)  
Increased blood alkaline phosphatase 2 (6.1) 
Rash maculo-papular 1 (3.0) 2 (6.9) 1 (3.4) 
Dermatitis exfoliative generalized 4 (13.8) 2 (6.9) 
Rash macular 2 (6.9) 
PTCL (n = 33)CTCL (n = 29)
Deaths, n (%) 26 (78.8) 14 (48.3) 
Disease 21 (63.6) 11 (37.9) 
Graft-versus-host disease§  1 (3.0) 
Pneumonia 1 (3.0) 
Pneumonitis 1 (3.0) 
Respiratory 1 (3.0) 
Infection due to leg amputation 1 (3.4) 
MRSA and GBS bacteremia 1 (3.4) 
Septic shock 1 (3.4) 
Unknown 1 (3.0)  
PTCL (n = 33)CTCL (n = 29)
Deaths, n (%) 26 (78.8) 14 (48.3) 
Disease 21 (63.6) 11 (37.9) 
Graft-versus-host disease§  1 (3.0) 
Pneumonia 1 (3.0) 
Pneumonitis 1 (3.0) 
Respiratory 1 (3.0) 
Infection due to leg amputation 1 (3.4) 
MRSA and GBS bacteremia 1 (3.4) 
Septic shock 1 (3.4) 
Unknown 1 (3.0)  

GBS, group B Streptococcus; MRSA, methicillin-resistant Staphylococcus aureus.

Up to 30 days following last dose.

One instance of pneumonitis in the PTCL cohort was grade 5.

Incidence was classed as hypersensitivity pneumonitis.

§

Death from graft-versus-host disease occurred 245 days posttransplant after last nivolumab dose.

Patient achieved a best overall response of CR on the study but stopped study treatment and subsequently received an allogeneic transplant. No details on the cause of death are known but the patient did not have PD.

In CheckMate 436, NBV demonstrated similar ORRs in both PTCL (45.5%; 15 of 33) and CTCL (41.4%; 12 of 29) cohorts and safety was similar to previous reports.9,11,17 ORRs in patients with PTCL were generally comparable with previous studies investigating PD-1 inhibitor monotherapy (nivolumab, 33%18; pembrolizumab, 33%10) and BV (41%19). Compared with studies that included patients with SS, ORR in patients with CTCL in CheckMate 436 was higher compared with nivolumab monotherapy (15%11), and similar to tislelizumab (45.5%20) and pembrolizumab (38%21) monotherapies. Additionally, ORR was lower compared with BV monotherapy in patients with CTCL excluding SS (65.6%12). Median DOR in PTCL (4.6 months) with NBV was comparable to nivolumab monotherapy (3.6 months)18; in patients with CTCL, median DOR was higher (27.0 months) than previously reported in one study (8.6 months) in patients with MF-CTCL.11 Similar durable remissions were observed with tislelizumab monotherapy in patients with R/R CTCL (11.3 months [95% CI, 2.8-11.3]; n = 11).20 

Hyperprogression has previously been observed in PTCL treated with nivolumab monotherapy18 and romidepsin plus pembrolizumab22; however, no cases were reported in this study. Further research is needed to determine if PD-1 inhibitors increase hyperprogression risk. Incidence of infusion-related reactions in CheckMate 436 was low, despite high incidence previously reported in patients with classical Hodgkin lymphoma treated with NBV.23 Although the study size was limited, given the modest ORRs observed with NBV compared with individual monotherapies, NBV is not supported in patients with PTCL and CTCL. Given disease heterogeneity, further evaluation is needed to determine which disease subtypes may benefit from this combination.

Acknowledgments: The authors thank the patients and their families for making this study possible, and the investigators (and clinical study teams) who participated in the study. The authors also thank Emily Pinter and Joels Wilson-Nieuwenhuis of Caudex, a division of IPG Health Medical Communications, for their assistance in the manuscript preparation.

This study was supported by Bristol Myers Squibb. Manuscript preparation was funded by Bristol Myers Squibb.

Contribution: P.L.Z. and A.S. contributed to the conception and design of the study; P.L.Z., G.S., A.J.M., A.S., A.M., P.M.B., N.M.-S., G.P.C., S.M.A., J.D.B., E.D.-D., N.A.J., D.C., S.F., J.L., and K.J.S. performed the research, collected data, and conducted data analysis and interpretation; N.A.J. contributed vital new reagents or analytical tools; and all authors reviewed and revised the manuscript, provided their final approval, and agree to be accountable for all aspects of the work.

Conflict-of-interest disclosure: P.L.Z. reports honoraria from AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Gilead, Incyte, Janssen, Kyowa Kirin, Merck Sharp & Dohme, Novartis, Roche, Sanofi, and Takeda. G.S. reports consulting fees from AbbVie, ATB Therapeutics, Bayer, BeiGene, Bristol Myers Squibb/Celgene, Debiopharm, Epizyme, Genentech/Roche, Genmab, Incyte, Ipsen, Janssen, Kite/Gilead, Loxo/Lilly, Merck, Molecular Partners, MorphoSys, Nordic Nanovector, Novartis, Nurix, Orna, Regeneron, and Takeda; and stock ownership in Owkin. A.J.M. reports consulting fees from Physician Education Resource and Seattle Genetics; honoraria from Academic Medical Education, Bio Ascend, Canadian Hematology Conference, Canadian Hematology Society, Harborside Press, Medscape, New York Oncology Hematology, Physician Education Resource, Puerto Rico Hematology and Medical Oncology Association, Seagen, Seattle Genetics, SOHO Brazil, Takeda, Tessa Therapeutics, and Triangle Insights; and advisory board participation with Affimed, Janpix, Kyowa Kirin, and Seattle Genetics. A.S. reports consulting fees from Incyte and Sanofi; honoraria from AbbVie, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Celgene, Eisai, Gilead, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sandoz, Servier, and Takeda; and advisory board participation with Bayer, Bristol Myers Squibb, Eisai, Gilead, Merck Sharp & Dohme, Pfizer, and Servier. A.M. reports research funding from Affimed, Celgene/Bristol Myers Squibb, Forty Seven/Gilead, Incyte, I-MAB, Innate, Juno/Bristol Myers Squibb, Kite/Gilead, Merck, Roche/Genentech, Seattle Genetics, Takeda, and TG Therapeutics; and consulting fees from AstraZeneca, BeiGene, Bristol Myers Squibb, Gilead, Incyte, Kyowa Kirin, MorphoSys/Incyte, Novartis, Pharmacyclics, Seattle Genetics, and TG Therapeutics. N.M.-S. reports research funding from AstraZeneca, Bristol Myers Squibb/Celgene, C4 Therapeutics, Corvus, Daiichi Sankyo, Dizal, Genentech/Roche, Innate, Secura, Verastem, and Yingli; and consulting fees from AstraZeneca, C4 Therapeutics, Daiichi Sankyo, Genentech/Roche, Karyopharm, Kyowa Hakko Kirin, Ono, Secura, and Verastem. G.P.C. reports consulting fees from ADC Therapeutics, AstraZeneca, BeiGene, Bristol Myers Squibb, Kite, Roche, and Takeda; honoraria from BeiGene, Gilead, Incyte, Kite, Roche, and Takeda; and travel support from Roche and Takeda. S.M.A. reports research funding from ADC Therapeutics, AstraZeneca, Bristol Myers Squibb, Pfizer, Regeneron, Seagen, and Takeda. J.D.B. reports research funding from Bristol Myers Squibb and honoraria from ADC Therapeutics, Epizyme, Genentech, Merck, and Seagen. E.D-D. reports honoraria from Takeda; travel support from Celgene/Bristol Myers Squibb and Takeda; and advisory board participation with BeiGene and Takeda. N.A.J. reports research funding from Gilead, Incyte, and Roche; consulting fees from AbbVie, AstraZeneca, BeiGene, Gilead, Merck, and Roche; honoraria from AbbVie, AstraZeneca, and BeiGene; and payment for expert testimony from Gilead. D.C. reports research funding from 4SC, Bayer, Celgene, Clovis, Leap, Lilly, MedImmune, and Roche, and advisory board participation with Ovibio. S.F. reports travel support from BeiGene. J.L. reports employment and stock with Seagen. J.K. and A.A. report employment and stock with Bristol Myers Squibb. R.W. reports employment with Bristol Myers Squibb. R.C. reports employment (at time of study) and stock with Bristol Myers Squibb. K.J.S. reports consulting fees from AbbVie, Bristol Myers Squibb, Janssen, and Seagen; steering committee participation with BeiGene; research funding from Bristol Myers Squibb and Roche; and data safety monitoring board participation with Regeneron. P.M.B. declares no competing financial interests.

Correspondence: Pier Luigi Zinzani, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli,” Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy; email: [email protected].

1.
Mak
V
,
Hamm
J
,
Chhanabhai
M
, et al
.
Survival of patients with peripheral T-cell lymphoma after first relapse or progression: spectrum of disease and rare long-term survivors
.
J Clin Oncol
.
2013
;
31
(
16
):
1970
-
1976
.
2.
Nabhan
C
,
Laney
J
,
Feliciano
J
,
Lee
CH
,
Klink
AJ
.
Treatment patterns and outcomes of relapsed/refractory peripheral T-cell lymphoma (RR-PTCL) patients treated in the community oncology setting
.
Blood
.
2018
;
132
(
suppl 1
). 1656-1656.
3.
Polgarova
K
,
Polivka
J
,
Kodet
O
,
Klener
P
,
Trneny
M
.
Retrospective analysis of 118 patients with cutaneous T-cell lymphomas: a single-center experience
.
Front Oncol
.
2022
;
12
:
884091
.
4.
Wilcox
RA
,
Feldman
AL
,
Wada
DA
, et al
.
B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders
.
Blood
.
2009
;
114
(
10
):
2149
-
2158
.
5.
Bossard
C
,
Dobay
MP
,
Parrens
M
, et al
.
Immunohistochemistry as a valuable tool to assess CD30 expression in peripheral T-cell lymphomas: high correlation with mRNA levels
.
Blood
.
2014
;
124
(
19
):
2983
-
2986
.
6.
Benner
MF
,
Jansen
PM
,
Vermeer
MH
,
Willemze
R
.
Prognostic factors in transformed mycosis fungoides: a retrospective analysis of 100 cases
.
Blood
.
2012
;
119
(
7
):
1643
-
1649
.
7.
Kim
YH
,
Prince
HM
,
Whittaker
S
, et al
.
Response to brentuximab vedotin versus physician's choice by CD30 expression and large cell transformation status in patients with mycosis fungoides: an ALCANZA sub-analysis
.
Eur J Cancer
.
2021
;
148
:
411
-
421
.
8.
Ramchandren
R
,
Domingo-Domenech
E
,
Rueda
A
, et al
.
Nivolumab for newly diagnosed advanced-stage classic Hodgkin lymphoma: safety and efficacy in the phase II CheckMate 205 study
.
J Clin Oncol
.
2019
;
37
(
23
):
1997
-
2007
.
9.
Pro
B
,
Advani
R
,
Brice
P
, et al
.
Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study
.
J Clin Oncol
.
2012
;
30
(
18
):
2190
-
2196
.
10.
Barta
SK
,
Zain
J
,
MacFarlane
AW
, et al
.
Phase II study of the PD-1 inhibitor pembrolizumab for the treatment of relapsed or refractory mature T-cell lymphoma
.
Clin Lymphoma Myeloma Leuk
.
2019
;
19
(
6
):
356
-
364.e3
.
11.
Lesokhin
AM
,
Ansell
SM
,
Armand
P
, et al
.
Nivolumab in patients with relapsed or refractory hematologic malignancy: preliminary results of a phase Ib study
.
J Clin Oncol
.
2016
;
34
(
23
):
2698
-
2704
.
12.
Horwitz
SM
,
Scarisbrick
JJ
,
Dummer
R
, et al
.
Randomized phase 3 ALCANZA study of brentuximab vedotin vs physician's choice in cutaneous T-cell lymphoma: final data
.
Blood Adv
.
2021
;
5
(
23
):
5098
-
5106
.
13.
Zinzani
PL
,
Santoro
A
,
Gritti
G
, et al
.
Nivolumab combined with brentuximab vedotin for relapsed/refractory primary mediastinal large B-cell lymphoma: efficacy and safety from the phase II CheckMate 436 study
.
J Clin Oncol
.
2019
;
37
(
33
):
3081
-
3089
.
14.
Santoro
A
,
Moskowitz
AJ
,
Ferrari
S
, et al
.
Nivolumab combined with brentuximab vedotin for relapsed/refractory mediastinal gray zone lymphoma: primary efficacy and safety analysis of the phase 2 CheckMate 436 study
.
Blood
.
2020
;
136
(
Suppl 1
):
44
-
45
.
15.
Cheson
BD
,
Fisher
RI
,
Barrington
SF
, et al
.
Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification
.
J Clin Oncol
.
2014
;
32
(
27
):
3059
-
3068
.
16.
Olsen
EA
,
Whittaker
S
,
Kim
YH
, et al
.
Clinical end points and response criteria in mycosis fungoides and Sezary syndrome: a consensus statement of the International society for cutaneous lymphomas, the United States cutaneous lymphoma consortium, and the cutaneous lymphoma task force of the European Organization for research and treatment of cancer
.
J Clin Oncol
.
2011
;
29
(
18
):
2598
-
2607
.
17.
Horwitz
S
,
O'Connor
OA
,
Pro
B
, et al
.
The ECHELON-2 trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma
.
Ann Oncol
.
2022
;
33
(
3
):
288
-
298
.
18.
Bennani
NN
,
Kim
HJ
,
Pederson
LD
, et al
.
Nivolumab in patients with relapsed or refractory peripheral T-cell lymphoma: modest activity and cases of hyperprogression
.
J Immunother Cancer
.
2022
;
10
(
6
):
e004984
.
19.
Horwitz
SM
,
Advani
RH
,
Bartlett
NL
, et al
.
Objective responses in relapsed T-cell lymphomas with single-agent brentuximab vedotin
.
Blood
.
2014
;
123
(
20
):
3095
-
3100
.
20.
Bachy
E
,
Savage
KJ
,
Huang
H
, et al
.
Tislelizumab, a PD-1 inhibitor for relapsed/refractory mature T/NK-cell neoplasms: results from a phase 2 study
.
J Clin Oncol
.
2022
;
40
(
suppl 16
). 7552-7552.
21.
Khodadoust
MS
,
Rook
AH
,
Porcu
P
, et al
.
Pembrolizumab in relapsed and refractory mycosis fungoides and Sézary syndrome: a multicenter phase II study
.
J Clin Oncol
.
2020
;
38
(
1
):
20
-
28
.
22.
Iyer
SP
,
Xu
J
,
Becnel
MR
, et al
.
A phase II study of pembrolizumab in combination with romidepsin demonstrates durable responses in relapsed or refractory T-cell lymphoma (TCL)
.
Blood
.
2020
;
136
(
Suppl 1
):
40
-
41
.
23.
Herrera
AF
,
Moskowitz
AJ
,
Bartlett
NL
, et al
.
Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma
.
Blood
.
2018
;
131
(
11
):
1183
-
1194
.

Author notes

The full-text version of this article contains a data supplement.

Supplemental data