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Table 2 Experimental agents and combinations of licensed agents in relapsed/refractory setting

From: Biomarker-driven management strategies for peripheral T cell lymphoma

Agent Target Trial/phase Subtype N ORR (%), CR (%) Median DOR (months) PFS (months) OS (months) AEs
Alisertib Aurora A kinase inhibitor SWOG1108 phase II [62] R/R PTCL or transformed MF (tMF),PTCL-NOS 35%, AITL 24%, ATLL 11% 37 30, 7 Not reported 3 8 Gr ≥ 3 AEs: neutropenia (32%), anemia (30%), thrombocytopenia (24%), febrile neutropenia (14%), mucositis (11%), rash (5%)
Lumiere phase III [87],alisertib vs. investigator’s choice R/R PTCL, PTCL-NOS 45%, AITL 22%,
ACLC 6% (ALK− 5% ALK+ 1%), EATL 2%, ENKTL 1%
120 33, 16 5 2.7 9.9 Gr ≥ 3 AEs (alisertib vs. comparator):neutropenia (43% vs 25%), thrombocytopenia (29% vs 27%), anemia (33% vs 11%)
Alemtuzumab Anti-CD52 mAb European phase II [20] R/R PTCL 14 36, 21.4 Not reported Not reported Not reported CMV reactivation in 6 pts
Pulmonary aspergillosis in 2 pts
EBV-related hemophagocytosis in 2 pts
5 treatment-related deaths
5-Azacitadine Hypo-methylating agent Retrospective series [38] R/R AITL (1 pt previously untreated), (41% with concomitant myeloid neoplasm) 12 75, 50 Not reported 15 21 TET2 mutations detected in all 12 patients
Crizotinib ALK ROS1 inhibitor Retrospective series [53] R/R ALK+ lymphoma, ALCL, ALK+ 82% 11 100, 100 Not reported 63.7% at 2 years 72.7% at 2 years No Gr ≥ 3 AEs
Phase I/II Children’s Oncology Group [52] R/R ALK+ ALCL
*Pediatric patients (aged 18 months–22 years old)
26 165 mg/m2:
83, 90 280 mg/m2: 83, 36
Not reported Not reported Not reported Gr ≥ 3 AEs: 165 mg/m2 22%, 280 mg/m2 70%
Duvelisib PI3K δ/γ inhibitor Phase I [56] R/R PTCL 16 50, 19 Not reported 4.4 Not reported Gr ≥ 3 AEs: transaminase increases (40% ALT, 17% AST), maculopapular rash (17%), neutropenia (17%)
Everolimus mTOR inhibitor Phase II [58] R/R PTCL + MF,PTCL-NOS 25%, ALCL 12.5%, AITL 6% ENKTL 6% 16 44 8.5 4.1 10.2 Gr ≥ 3 AEs : hematologic toxicity 37.5%
Lenalidomide Immuno-modulator EXPECT, phase I/II [50] R/R PTCL, AITL 48%, PTCL-NOS 37%, ALCL 6% 54 22, 11
AITL:
31, 15
3.6
AITL: 3.5
2.5
AITL: 4.6
Not reported Gr ≥ 3 AEs experienced by 54%
12 treatment-related deaths: acute respiratory distress syndrome, dyspnea, lung infiltration, neutropenic sepsis, pneumonia and cerebral ischemia (n = 1 each)
   ATLL-002 phase II [51] R/R ATLL, acute 58%, lymphomatous 27%, chronic 15% 26 42, 19 Not reported 3.8 20.3 Gr ≥ 3 AEs: neutropenia (65%), leukopenia (38%), lymphopenia (38%), thrombocytopenia (23%)
Nivolumab Anti-PDL-1 mAb Phase Ib [48] R/R PTCL, AITL 50%, PTCL-NOS 25%, ALCL, ALK− 8% 12 33, 17 3.6 1.9 7.9 Immune-mediated AEs in 34%; 53.5% required treatment for immune-mediated AE
Phase II [47] ATLL: 1 acute, 1 lymphomatous, 1 chronic 3 n/a n/a n/a n/a All 3 patients developed rapid progression of disease after the 1st dose
Pembrolizumab Anti-PDL-1 mAb Retrospective series [88] R/R EBV+ NKTCL, failing L-asparaginase 7 100, 71.4 Not reported Not reported Not reported 1 patient (post-alloHSCT) developed grade 2 rash; no other AEs
Phase II [49] R/R PTCL 18 33, 27 2.9 3.2 10.6 Trial halted early after preplanned interim futility analysis
Grade ≥ 3 rash (17%), grade ≥ 3 pneumonitis (11%)
Romidepsin + henalidomide   Phase I/II [32], phase II ongoing NCT022325-16 R/R TCL, 10 CTCL, 11 PTCL 21 50 Not reported 13.5 weeks* Not reached Grade ≥ 3 AEs: neutropenia (48%), thrombocytopenia (38%), anemia (33%), electrolyte abnormalities (K, Phos, glucose, Mg (43%)
Romidepsin + lenalidomide + carfilzomib   Phase Ib/IIa [33] R/R TCL, PTCL-NOS 47%, AITL 21% 19 50, 31
AITL: 80% CR
9.8 weeks* 9.7 weeks* Not reached Grade ≥ 3 AEs in ≥ 10% of patients: neutropenia, thrombocytopenia
Romidepsin + pralatrexate   Phase I/II [34] R/R lymphomas
,TCL 62%, ATLL 21%, ALCL, ALK− 10%
23 71, 40 4.29 4.4 12.4 Grade 4 AEs: thrombocytopenia (14%), neutropenia (10%), sepsis (7%), fever (3%), and pneumonia (3%)
Romidepsin + azacitadine   Phase I [39] R/R lymphomas, TCL 35%, AITL 10%, ATLL 6% 31 32, 23
TCL: 73, 55 AITL: 100% CR
2.5; TCL: not reached Not reached Not reported Grade ≥ 3 AEs: thrombocytopenia (27%), neutropenia (42%), lymphopenia (42%), hypotension (12%), hyponatremia (8%)
Duvelisib + romidepsin + bortezomib   Phase I/II [57]
Arm A: duvelisib + romidepsinArm B: duvelisib + bortezomib
R/R PTCL + CTCL Arm A: 22Arm B: 14 Arm A: 55, 27Arm B: 36, 21 Arm A: 8.8
Arm B: 3.5
Arm A: 9.1 (all patients)
Arm B: 9.3 (all patients)
Not reported Arm A: 65% with Gr ≥ 3 AEs: increased ALT/AST (15%), neutropenia (18%), hyponatremia (12%)
Arm B: 45% with Gr ≥ 3 AEs: neutropenia (18%), 1 pt with Stevens-Johnson syndrome