Table 1.
Clinical activity of systemic therapies in CTCL* by disease subtype (clinical stage, MF vs SS), compartments (skin, LN, blood), ±LCT; tolerability
| Treatment | N; subtype | Global/composite clinical activity of all compartments* | Skin activity | LN activity | Blood activity | LCT included | Tolerability factors in chronic therapy | ||
|---|---|---|---|---|---|---|---|---|---|
| ORR/CR % (n/N) | DOR, median | PFS, median | |||||||
| Standard therapies | |||||||||
| Bexarotene†,22 (300 mg/m2 = optimal dose) | 56; MF/SS IIB-IV; SS (17/56) |
45% (25/56)/1 CR | 42.7 weeks | 13.9 weeks | Skin RR = primary end point: IIB, 57% (13/23); III, 32% (6/19); IVA, 44% (4/9); IVB, 40% (2/5); SS, 24% (4/17, all doses) |
Limited LN data: Of 25 skin OR, 7 w/clinical LAD - 3/7 PR or CR 4/7 PD |
Of 17 SS, 8 had partial Sezary data: 4/8 PR 3/8 SD 1/8 PD |
N/a | Hyperlipidemia |
| Extracorporeal photopheresis‡,24 | 51; MF/SS III-IV; SS (39/51) |
63% (32/51)/8 CR | 22.4 months | N/a | Compartment-specific data not reported but 16% CR w/clearing of blood Sezary disease | N/a | None | ||
| Vorinostat63 | 74; MF/SS IB-IV; SS (30/74) |
30% (22/74)/1 CR after 281 days | >185 days | TTP median 148 days | Skin RR = primary end point: IB/IIA, 31% (4/13); IIB-IV, 30% (18/61); skin tumors, 23% (5/22); SS, 33% (10/30) |
LN RR 42% (10/24) | 14/27 SS w/SC reduction >25% | Yes | Fatigue, dysgeusia, ↓platelets |
| Romidepsin14 | 96; MF/SS IB-IV; SS (37/96) |
34% (33/96)/6 CR; SS (B1-2), 32% (12/37) |
15 months | TTP median 8 months | Skin RR 40% (38/96) | LN response 35% (13/37) by RECIST | Blood RR 38% (14/37, 2 CR); B2, 46% (6/13, 2 CR) | Yes | Fatigue, dysgeusia, ↓platelets |
| Pralatrexate§,37 (optimal CTCL dose 15 mg/m2 weekly 3/4) | 29; CTCL IB-IV; SS (8/29) |
45% (13/29)/1 CR | Not reached; 73% cont OR at 6 months | Not reached; 388 days >15 mg/m2 | Compartment-specific data not reported, response by stage: MF by stage IB 60% (3/5); IIB 67% (4/6); IVA 60% (3/5); SS 25% (2/8) |
Yes | Mucositis | ||
| Brentuximab11 | 48; MF IA-IV; CD30 > 10% (no SS) | 65% (31/48)/ 5 CR; ORR4 LCT 65% (11/17) |
15.1 months; MF/ALCL | 15.9 months; LCT 15.5 months | Skin RR 77% (37/48); median DOR 20.6 months, MF/ALCL |
2 w/LN+, stage IVA: ORR 100% (2/2, 1 CR) | Excluded B2/SS | Yes (17/48) | PN |
| Mogamulizumab¶,13 | 186; MF/SS IB-IV; SS (81/186) |
28% (52/186)/6 CR; MF 21% (22/105); SS 37% (30/81) | 14.1 months; MF 13.1 months; SS 17.3 months | 7.7 months | Skin RR 42% (78/186); median TTR 3.0 months; median DOR 20.6 months |
LN RR 17% (21/124); median TTR 3.3 months; median DOR 15.5 months |
Blood RR 68% (83/122, 54 CR); median TTR 1.1 months; median DOR 25.5 months | No (LCT excluded) | Rash |
| Pembrolizumab41 | 24; MF/SS IIB-IV (23/24); SS (15/24) |
38% (9/24)/2 CR; SS 27% (4/15); LCT 25% (1/4) | Not reached; median follow-up 58 weeks | Not reached; PFS at 1 year, 65% | Skin RR 38% (9/24); 6/24, >90% skin clearing | N/a | Baseline w/B2, n = 6, 17% (1/6) | Yes (4/24) | irAE (colitis, pneumonitis) |
| Liposomal doxorubicin§,39 (20 mg/m2, day 1, day 15, 28-day cycle) | 49; MF IIB-IV (no SS) |
41% (20/49)/3 CR | 6 months | 6.2 months; TTP median 7.4 months | Skin RR 53% (26/49); best PR/CR | LN ± visceral disease had lower RR than skin-only (22% vs 52%) | Excluded SS | Yes | |
| Gemcitabine§,40 (1000 mg/m2, day 1, 8, 15) | 31; MF/SS; SS (11/33) | 65% (20/31)/3 CR; LCT 54% (7/13); SS 73% (8/11) | 4.1 months | N/a | Compartment-specific data not reported but case examples with activity in LN/blood disease | Yes (13/31) | |||
| Investigative therapies (w/peer-reviewed papers) | |||||||||
| Anti-KIR3DL2 antibody (lacutamab), phase 1/2 study data (ongoing pivotal trial in SS)25 | 44; SS (35/44); MF IB-IV (8/44) | SS, 43% (15/35); MF, 13% (1/8); LCT no OR | 13.8 months; SS 13.8 months; MF 6.9 months | 8.2 months; SS 11.7 months, MF 3.9 months | Of SS: skin RR 51% (18/35, 3 CR) | Of SS: LN RR 11% (2/18, 1 CR) | Of SS: blood RR 56% (19/34, 9 CR) | Yes (6/35 SS, 5/8 MF) | Well tolerated |
| Duvelisib64 | 19; MF/SS; MF (13/19); SS (5/19) | 32% no CR; MF 38% (5/13); LCT 25% (1/4); SS 20% (1/5) | n/a; DOR range 0.7-10.1 months; TTR 2.4 months |
4.5 months | Compartment-specific data not reported | Yes (4/19) | ↑LFTs | ||
| Lenalidomide65 | 32; MF/SS IB-IV; SS (11/32) |
28% (9/32) no CR | 10 months; TTR 25 mg, 2 months; 10 mg, 4 months | 8 months | Skin RR 53% (10/19) MF IB-IV | Reports activity, no details | Blood RR 38% (5/13) | N/a | Fatigue, skin flares, transient ↑blood SCs |
Response assessment tools and/or criteria for clinical end points may vary across CTCL trials.
Time to response is longer than other listed treatments, 300 mg/m2, TTR = 15.7 weeks (180 days), >300 mg/m2, TTR = 8.4 weeks (59 days); poor details on extracutaneous disease sites (4/9 entered as stage IVB had LN+ only); “rate of PD” = 39% (22/56) and 32% (12/38) for 300 mg/m2 and >300 mg/m2; median TTR for other treatment ~2 cycles.
Median time to response 8 months.
Caution when used with RT, especially TSEBT.
Caution when used to bridge to allogeneic HSCT (possible risk of severe GVHD).
ALCL, anaplastic large cell lymphoma; DOR, duration of response; irAE, immune-related adverse event; LFT, liver function test; n/a, not applicable; OR, odds ratio; PFS, progression-free survival; PN, peripheral neuropathy; RECIST, response evaluation criteria in solid tumors; RT, radiation therapy; SD, stable disease; TTR, time to response; TTP, time to progression.