Clinical characteristics of CLL patients diagnosed with RS
| Patient . | 1 . | 2 . | 3 . | 4 . |
|---|---|---|---|---|
| At the time of CLL diagnosis | ||||
| Age, y | 51 | 69 | 65 | 71 |
| Sex | Female | Male | Male | Female |
| WBC ×109/L | 57 | 4.9 | 28.4 | 9.6 |
| Hemoglobin, g/dL | 14 | 13.4 | 12.5 | 12 |
| Platelet count ×109/L | 370 | 197 | 155 | 218 |
| β2 microglobulin, mg/dL | 1.72 | 1.91 | N/A | N/A |
| Rai stage | I | I | 0 | I |
| IGHV mutation status | Unmutated | Unmutated | Unmutated | Unmutated |
| IGHV4-39 gene usage | No | No | Yes | No |
| ZAP-70 expression ≥20% | Yes | Yes | Yes | Yes |
| CD49d expression ≥30% | No | No | No | Yes |
| CD38 expression ≥30% | No | No | N/A | No |
| FISH | del13q | Normal | Normal | del17p |
| CLL therapy | 1. Rituximab, alemtuzumab, and β-glucan 2. Pentostatin, cyclophosphamide, and rituximab 3. Everolimus and alemtuzumab | 1. Bendamustine and rituximab | 1. Pentostatin, cyclophosphamide, and rituximab | 1. Bendamustine and rituximab 2. Everolimus and alemtuzumab 3. Methylprednisolone and ofatumumab 4. Methylprednisolone and alemtuzumab |
| Time from last CLL therapy to RS diagnosis (months) | 8 | 2 | 24 | <1 |
| At the time of DLBCL diagnosis | ||||
| Age, y | 62 | 74 | 68 | 74 |
| WBC ×109/L | 131.6 | 80.3 | 6.3 | 2.6 |
| Hemoglobin, g/dL | 10.8 | 9.2 | 14.5 | 9.8 |
| Platelet count ×109/L | 116 | 111 | 149 | 169 |
| LDH, U/L (normal:111-222 U/L) | 810 | 236 | 204 | 466 |
| RS prognosis score4 | 1 (low) | 2 (low-intermediate) | 0 (low) | 3 (high-intermediate) |
| Type of biopsy specimen | Bone marrow aspirate and biopsy | Core biopsy of T7 bone | Left neck excisional biopsy | Bone marrow aspirate and biopsy |
| Subtype (GCB vs ABC) | ABC | ABC | ABC | ABC |
| MYC rearrangement by FISH | Negative | Not done | Not done | Negative |
| EBV status | N/A | N/A | N/A | Negative |
| Initial therapy for RS | 1. R-CHOP (2 cycles, PR) 2. R-ICE (1 cycle, PD) 3. Palliative therapy with methylprednisolone (twice per wk for 6 wks, SD) | 1. R-CHOP (2 cycles, PD) 2. R-EPOCH (2 cycles, PD) | 1. R-CHOP (2 cycles, PD) 2. R-ICE (3 cycles, PR) 3. R-DHAP (2 cycles, PD) | None |
| Ibrutinib dose, mg per day | 420 | 140 | 420 | 420 |
| Concomitant therapy with ibrutinib | Methylprednisolone 1000 mg Intravenously (twice per wk for 1 mo, once per wk for 1 mo, and once every 2 wks for 1 mo) | Methylprednisolone 1000 mg Intravenously (twice per wk for 2 mo) | None | None |
| Duration of ibrutinib therapy, months | 8.5 | 3.7 | 2.8 | 10.8 |
| Best response achieved | PR | Clinical benefit* | CR | PR |
| Status at most recent follow-up | Progressive DLBCL | Death | Ongoing complete remission | Progressive CLL |
| Patient . | 1 . | 2 . | 3 . | 4 . |
|---|---|---|---|---|
| At the time of CLL diagnosis | ||||
| Age, y | 51 | 69 | 65 | 71 |
| Sex | Female | Male | Male | Female |
| WBC ×109/L | 57 | 4.9 | 28.4 | 9.6 |
| Hemoglobin, g/dL | 14 | 13.4 | 12.5 | 12 |
| Platelet count ×109/L | 370 | 197 | 155 | 218 |
| β2 microglobulin, mg/dL | 1.72 | 1.91 | N/A | N/A |
| Rai stage | I | I | 0 | I |
| IGHV mutation status | Unmutated | Unmutated | Unmutated | Unmutated |
| IGHV4-39 gene usage | No | No | Yes | No |
| ZAP-70 expression ≥20% | Yes | Yes | Yes | Yes |
| CD49d expression ≥30% | No | No | No | Yes |
| CD38 expression ≥30% | No | No | N/A | No |
| FISH | del13q | Normal | Normal | del17p |
| CLL therapy | 1. Rituximab, alemtuzumab, and β-glucan 2. Pentostatin, cyclophosphamide, and rituximab 3. Everolimus and alemtuzumab | 1. Bendamustine and rituximab | 1. Pentostatin, cyclophosphamide, and rituximab | 1. Bendamustine and rituximab 2. Everolimus and alemtuzumab 3. Methylprednisolone and ofatumumab 4. Methylprednisolone and alemtuzumab |
| Time from last CLL therapy to RS diagnosis (months) | 8 | 2 | 24 | <1 |
| At the time of DLBCL diagnosis | ||||
| Age, y | 62 | 74 | 68 | 74 |
| WBC ×109/L | 131.6 | 80.3 | 6.3 | 2.6 |
| Hemoglobin, g/dL | 10.8 | 9.2 | 14.5 | 9.8 |
| Platelet count ×109/L | 116 | 111 | 149 | 169 |
| LDH, U/L (normal:111-222 U/L) | 810 | 236 | 204 | 466 |
| RS prognosis score4 | 1 (low) | 2 (low-intermediate) | 0 (low) | 3 (high-intermediate) |
| Type of biopsy specimen | Bone marrow aspirate and biopsy | Core biopsy of T7 bone | Left neck excisional biopsy | Bone marrow aspirate and biopsy |
| Subtype (GCB vs ABC) | ABC | ABC | ABC | ABC |
| MYC rearrangement by FISH | Negative | Not done | Not done | Negative |
| EBV status | N/A | N/A | N/A | Negative |
| Initial therapy for RS | 1. R-CHOP (2 cycles, PR) 2. R-ICE (1 cycle, PD) 3. Palliative therapy with methylprednisolone (twice per wk for 6 wks, SD) | 1. R-CHOP (2 cycles, PD) 2. R-EPOCH (2 cycles, PD) | 1. R-CHOP (2 cycles, PD) 2. R-ICE (3 cycles, PR) 3. R-DHAP (2 cycles, PD) | None |
| Ibrutinib dose, mg per day | 420 | 140 | 420 | 420 |
| Concomitant therapy with ibrutinib | Methylprednisolone 1000 mg Intravenously (twice per wk for 1 mo, once per wk for 1 mo, and once every 2 wks for 1 mo) | Methylprednisolone 1000 mg Intravenously (twice per wk for 2 mo) | None | None |
| Duration of ibrutinib therapy, months | 8.5 | 3.7 | 2.8 | 10.8 |
| Best response achieved | PR | Clinical benefit* | CR | PR |
| Status at most recent follow-up | Progressive DLBCL | Death | Ongoing complete remission | Progressive CLL |
EBV, Epstein-Barr virus; FISH, fluorescence in-situ hybridization; IGHV, immunoglobulin heavy chain genes; LDH, lactate dehydrogenase; N/A, not available; PD, progressive disease; PR, partial response; SD, stable disease; WBC, white blood cell count; ZAP-70, zeta-chain–associated protein kinase 70.
Documentation of reduction in lymphadenopathy by physical examination. The patient died of pulmonary mucormycosis (diagnosed prior to ibrutinib initiation) after 15 weeks of therapy and prior to repeat imaging to allow for response assessment.