Summary of clinical characteristics, best responses, and biomarker evaluation in RT patients
| RT patient . | CLL biology and therapy . | RT biology and therapy . | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CLL FISH . | TP53 mut . | IGHV . | IGHV subset . | CLL therapy prior to transformation and best response (DOR) . | Prior RT therapy before Pembro and response (DOR) . | % PD-1 . | % PD-L1 . | RT vs CLL clone . | EBER . | Best response to Pembro . | Duration of Pembro therapy . | |||
| RS1 | Normal | — | UM | 4-39*01 | PCR | CR (2 y) | RCHOP, RICE, RDHAP, Ibr | PD to chemo, PR to Ibr (5 mo), then PD | 52.3 | 17.4 | Rel | — | CR | 16 mo, ongoing |
| RS2 | del(17p) | — | UM | 3-30*03 | Ibr | PR-L (1.5 y) | None | 45.2 | 3.6 | Rel | — | PR | 12 mo, ongoing | |
| RS3 | del(13q) | + | UM | 4-39*01 | Ibr | PR (5 mo) | RCHOP | PR (3 mo), then PD | 22.8 | 1.6 | Rel | — | SD, skin lymphoma response | 2 mo, off therapy |
| RS4 | Normal | n/a | M | 4-1*02 | Untreated | REPOCH, Ibr | PD | n/a | n/a | n/a | n/a | SD, nodal reduction | 2 mo, off therapy | |
| RS5 | del(13q) | — | M | 1-18*01 | Untreated | RCHOP | PD | n/a | n/a | n/a | n/a | PD | 3 mo, off therapy | |
| RS6 | del(13q) | + | UM | 4-61*01 | Ibr | SD (6 mo) | None | 47.2 | 30.4 | n/a | — | PR | 4 mo, off therapy | |
| RS7 | del(17p) | — | UM | 1-2*02 | Untreated | RCHOP, auto-SCT | CR (4.5 y), then PD | n/a | n/a | n/a | + | SD | 5 mo, off therapy | |
| RS8 | Normal | — | UM | 3-11*01 | Untreated | RCHOP, RICE, auto-SCT, RDHAP | CR (1 y), then PD | 1.0 | 4.0 | Rel | — | SD | 3 mo, off therapy | |
| RS9 | del(17p) | — | UM | 3-21*01 | Ibr | CR (2 y) | None | 21.4 | 34.0 | Rel | — | PMR | 3 mo, ongoing | |
| RT patient . | CLL biology and therapy . | RT biology and therapy . | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CLL FISH . | TP53 mut . | IGHV . | IGHV subset . | CLL therapy prior to transformation and best response (DOR) . | Prior RT therapy before Pembro and response (DOR) . | % PD-1 . | % PD-L1 . | RT vs CLL clone . | EBER . | Best response to Pembro . | Duration of Pembro therapy . | |||
| RS1 | Normal | — | UM | 4-39*01 | PCR | CR (2 y) | RCHOP, RICE, RDHAP, Ibr | PD to chemo, PR to Ibr (5 mo), then PD | 52.3 | 17.4 | Rel | — | CR | 16 mo, ongoing |
| RS2 | del(17p) | — | UM | 3-30*03 | Ibr | PR-L (1.5 y) | None | 45.2 | 3.6 | Rel | — | PR | 12 mo, ongoing | |
| RS3 | del(13q) | + | UM | 4-39*01 | Ibr | PR (5 mo) | RCHOP | PR (3 mo), then PD | 22.8 | 1.6 | Rel | — | SD, skin lymphoma response | 2 mo, off therapy |
| RS4 | Normal | n/a | M | 4-1*02 | Untreated | REPOCH, Ibr | PD | n/a | n/a | n/a | n/a | SD, nodal reduction | 2 mo, off therapy | |
| RS5 | del(13q) | — | M | 1-18*01 | Untreated | RCHOP | PD | n/a | n/a | n/a | n/a | PD | 3 mo, off therapy | |
| RS6 | del(13q) | + | UM | 4-61*01 | Ibr | SD (6 mo) | None | 47.2 | 30.4 | n/a | — | PR | 4 mo, off therapy | |
| RS7 | del(17p) | — | UM | 1-2*02 | Untreated | RCHOP, auto-SCT | CR (4.5 y), then PD | n/a | n/a | n/a | + | SD | 5 mo, off therapy | |
| RS8 | Normal | — | UM | 3-11*01 | Untreated | RCHOP, RICE, auto-SCT, RDHAP | CR (1 y), then PD | 1.0 | 4.0 | Rel | — | SD | 3 mo, off therapy | |
| RS9 | del(17p) | — | UM | 3-21*01 | Ibr | CR (2 y) | None | 21.4 | 34.0 | Rel | — | PMR | 3 mo, ongoing | |
Percent PD-1 and PD-L1 expression were quantitatively analyzed by calculating positive-cell percentage of the corresponding antigens in all cells of tumor samples. All 6 RT patients (RS1, RS2, RS3, RS6, RS8, and RS9) tested, did not have copy number gain nor amplification in chromosome 9p24. The RT disease of RS6 had PR to single-agent pembrolizumab for 4 months before he came off therapy due to thrombocytopenia caused by CLL marrow progression. RS3, RS4, RS5, RS7, and RS8 came off therapy due to lack of sufficient durable responses or alternative therapy.
auto-SCT, autologous stem cell transplant; EBER, Epstein-Barr virus–encoded RNA; Ibr, ibrutinib; M, mutated IGHV; n/a, not available; PCR, pentostatin, cyclophosphamide, and rituximab; Pembro, pembrolizumab; PR-L, PR with lymphocytosis; RCHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; RDHAP, rituximab, cisplatin, cytarabine, and dexamethasone; Rel, clonally related between CLL and RT clones; REPOCH, rituximab, etoposide, doxorubicin, cyclophosphamide, vincristine, and prednisone; RICE, rituximab, ifosfamide, carboplatin, and etoposide; TP53 mut, TP53 mutation; UM, unmutated IGHV.