Table 1:
Patient profiles and treatment response
| Case | Age (years)/ gender1 | ARV/yrs since KS diagnosis & Stage | # of prior lines of therapy | HIV-1 viral load (copies/mL) | Best response | PFS months2 | DNA (characterized) alterations (no VUSs) Tumor mutation burden (TMB in mutations/megabase)* | Immunohistochemistry for PD-L1 and PD1 | Comments | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pre-therapy | Post-therapy | (Tissue NGS)* | ctDNA** | PD-L1 /PD1 TIL*** | PD-L1/PD1 tumor*** | |||||||
| 1 | 63 M | Yes/4 Cutaneous, LN (T0I0S1) |
2 (Bortezomib, Lenalidomide) | <20 | 29 | SD | 6.5+ | KRAS Q61H TP53 R273C TMB = 4 | TP53 R175H TP53 K164R TP53 S240R TP53 F134* TP53 G244S | Negative/5% | Negative/not reported | History of DLBCL in CR s/p ASCT (reached maximum lifetime dose of doxorubicin). Platelets increased from 30 to 90 K/ul); hemoglobin, from 8 to 11 g/dl |
| 2 | 47 M | Yes/12 Cutaneous (T0I0S1) |
1 (Lenalidomide) | ND | 92 | PR | 5+ | NA | No alterations | NA | NA | Regressed nodularity, hyperpigmentation and size |
| 3 | 55 M | Yes/9 Cutaneous w/ lymphedema (T1I0S1) |
4 (Liposomal doxorubicin, Lenalidomide, Paclitaxel, Bortezomib) | ND | ND | PR | 3.5+ | NA | NF1 Q1370fs | NA | NA | Regressed nodularity and hyperpigmentation. |
| 4 | 44 M | Yes/1 Cutaneous (T0I1S1) |
0 | 22 | <20 | SD | 6.5+ | TLL2 G465E TMB = 3 | No alterations | Negative/50% | Negative/not reported | Refused chemotherapy. |
| 5 | 49 M | Yes/0 Cutaneous (T0I1S1) |
0 | 116,706 | 118 | PR | 6.5+ | Inadequate tissue | N/A | Negative/20% | Negative/not reported | Concomitant active TB at the time of KS therapy. Lesions regressed in size, nodularity, pigmentation and are less painful. Some lesions have resolved. |
| 6 | 42 M | Yes/0 GI (T1IS1) |
0 | 24 | 64 | CR | 5.5+ | Inadequate tissue | No characterized alterations (ATM L2698F VUS found) | Negative/ negative | Negative/ negative | Refused chemotherapy. Bloody diarrhea resolved. Repeat colonoscopy was negative |
| 7 | 41 M | Yes/6 Cutaneous, LN, lung (T1I1S1) |
3 (Liposomal doxorubicin, Paclitaxel, Bortezomib) | ND | 84 | SD | 3.5+ | PTPN6M1 TMB = 1 | No alterations | NA | NA | Some lesions have flattened, regressed nodularity and hyperpigmentation |
| 8 | 38 M | Yes/2 Cutaneous, LN, bowel (T1I1S1) |
1 (Liposomal doxorubicin) | 549,704 | 1,210,000 | PR | 1.5+ | NA | NA | NA | NA | Improved right leg lymphedema, abdominal and leg pain. |
| 9 | 33 M | Yes/8 Cutaneous, GI (T1I1S1) |
1 ((Liposomal doxorubicin) | ND | <20 | PR | 1.5+ | NA | No alterations | NA | NA | All lesions have improved; some lesions have resolved completely. |
Tissue next generation sequencing (NGS) performed by Foundation (see Methods).
Denotes Guardant360 plasma-derived circulating tumor DNA sequencing (see Methods).
Antibody used: PD-1/PD-L1 status was determined with immunohistochemistry (IHC) performed by Foundation Medicine, INC (Programmed Death 1 (clone NAT105 by CellMarque) Programmed Death Ligand 1, CD274 (clone SP142 by Spring Bioscience)). 1Patient’s age at start of treatment with PD1 blockade. 2+ means response is ongoing at the time of data censoring. Abbreviations: ARVs = anti-retrovirals; ASCT = autologous stem cell transplant; CR = complete response; DLBCL = Diffuse large B-Cell lymphoma; Dx = diagnosis; GI = gastrointestinal; HHV8 = human herpes virus 8; HIV = human immunodeficiency virus; KS = Kaposi sarcoma; LN = lymph nodes: M = male; MB = megabase; N/A = not available; ND = not detected; NGS = next generation sequencing; PFS = progression free survival; PR = partial response; RNA = ribonucleic acid; R/R = relapsed /refractory; SD = stable disease; TIL = tumor infiltrating lymphocytes; TMB = tumor mutational burden; VL = viral load; VUS = variants of unknown significance