Table 3.
Summary of patient characteristics, causes of discontinuation, and outcomes of patients after discontinuing ibrutinib (n = 33)
| Patients | Patient characteristics | Cause of discontinuation | Outcome of patients after ibrutinib | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, years | Zap-70 Status | β2 M (mg/L) | IGHV mutation status | Fluorescence in situ hybridization | Number of prior therapies | Duration of ibrutinib, months | Survival status | Survival post-ibrutinib, months | |||
| Patients who transformed (n = 7) | |||||||||||
| 1‡ | 57 | + | 6.8 | UM | del11q + del13q | 5 | 13.1 | Dead | 0.0 | Histiocytic sarcoma transformation | Died on study |
| 2 | 52 | ND | 6 | UM | del13q | 4 | 4.5 | Dead | 0.9 | Richter transformation | Died |
| 3‡ | 72 | + | 4 | UM | del17p | 3 | 21.9 | Alive | 2+ | Richter transformation | On small molecule clinical trial |
| 4 | 73 | + | 12 | UM | del17p | 1 | 2 | Dead | 2.1 | Richter transformation | Chemoimmunotherapy ×1* |
| 5 | 60 | + | 10 | UM | del11q | 2 | 13.1 | Dead | 2.6 | Richter transformation | R-MP (1 course) |
| 6 | 65 | + | 2.1 | UM | del17p | 0 | 10 | Dead | 3.1 | Richter transformation | Chemoimmunotherapy* |
| 7 | 63 | + | 2 | UM | del17p + 11q + 13q | 4 | 9.4 | Dead | 15.0 | Richter transformation | Chemoimmunotherapy×1* |
| Patients who progressed not transformed (n = 7) | |||||||||||
| 1‡ | 73 | + | 4 | UM | del17p | 1 | 14.2 | Dead | 1.6 | Progressive disease | Chronic obstructive pulmonary disease, infections, no further treatment of CLL |
| 2‡ | 78 | — | 5.2 | UM | del17p | 2 | 22.5 | Alive | 1.8+ | Progressive disease | Ofatumumab |
| 3‡ | 52 | + | 3 | UM | del13q | 2 | 21.4 | Alive | 1.9+ | Progressive disease | On small molecule clinical trial |
| 4‡ | 36 | — | 5.9 | UM | del11q | 2 | 6.9 | Dead | 2.1 | Progressive disease | Infections, pneumonia, no further treatment of CLL |
| 5 | 63 | + | 5.1 | UM | del11q + 13q | 5 | 38.7 | Dead | 2.8 | Progressive disease | Pneumonia |
| 6 | 56 | + | 4.1 | ND | del17p + 13q | 2 | 33.1 | Alive | 11.5+ | Progressive disease | R-MP (4 infusions, PR), on small molecule clinical trial |
| 7 | 83 | — | 10.8 | UM | del17p, +12, 13q | 4 | 18.5 | Alive | 14.4+ | Progressive disease | Ofatumumab |
| Patients who discontinued because of stem cell transplantation (n = 3) | |||||||||||
| 1 | 61 | + | 2.3 | UM | del17p + del 11q | 3 | 11.7 | Dead | 0.1 | Stem cell transplantation | Died of graft vs host disease |
| 2‡ | 64 | — | 2.4 | UM | Negative | 3 | 12.9 | Dead | 4.2 | Stem cell transplantation | Complications of transplant |
| 3‡ | 63 | + | 5.1 | UM | Del17p | 1 | 11.9 | Alive | 11+ | Stem cell transplantation | Remission post-SCT |
| Patients who discontinued because of adverse events or sudden death (n = 14) | |||||||||||
| 1‡ | 61 | + | 5.1 | UM | Del17p | 1 | 11 | Dead | 0 | Pseudomonas sepsis and bronchiectasis | No further treatment |
| 2 | 64 | + | 10.8 | ND | Del13q | 3 | 20 | Dead | 0 | Recurrent fungal pneumonia, altered mental status | No further treatment, died on study |
| 3 | 50 | ND | 3.7 | UM | Negative | 1 | 6 | Dead | 0 | Sudden death† | Died on study |
| 4 | 64 | + | 3 | UM | Trisomy 12 | 0 | 6.2 | Dead | 0 | Suicide | Died on study |
| 5‡ | 67 | — | 2.6 | UM | Del11q | 1 | 16.4 | Dead | 0 | Sudden death† | Died on study |
| 6‡ | 76 | + | 6 | UM | Del17p | 2 | 2.1 | Dead | 0.2 | Extensive aspergillosis | Multifocal aspergillosis, no further treatment of CLL |
| 7‡ | 68 | — | 3.9 | UM | del11q | 2 | 21.5 | Alive | 0.3+ | Diarrhea, subdural hematoma, | Plan to restart ibrutinib |
| 8 | 68 | — | 6 | M | del17p + del11q + del13q | 5 | 31.9 | Dead | 1 | Diarrhea and pneumonia with DIC | No treatment |
| 9‡ | 62 | + | 5.4 | UM | Del17p | 0 | 17 | Dead | 1.8 | Recurrent ear bleeding, past history of cancer oropharynx | Died on study, but off ibrutinib |
| 10‡ | 82 | + | 4.1 | UM | Del17p | 1 | 8.4 | Dead | 4 | Comorbidities and recurrent infections, chronic obstructive pulmonary disease | No further treatment |
| 11 | 66 | ND | 4.3 | UM | del17p +12 del13q | 7 | 3.9 | Dead | 5 | Gastrointestinal bleeding, acquired von Willebrand disease, accelerated CLL | Hyper-CVAD with ofatumumab |
| 12‡ | 57 | + | 3.2 | M | Del17p | 3 | 6 | Dead | 12.8 | Recurrent oral ulcers, intolerance | OFAR1 cycle, ibrutinib restarted |
| 13 | 50 | ND | 2.2 | UM | del13q | 3 | 16.1 | Alive | 24.1+ | Diarrhea, colitis | Ofatumumab and MP, progressed with ascites and C1 OFAR-2 again on ibrutinib |
| 14 | 68 | + | 3.4 | UM | del13q | 4 | 1.9 | Dead | 41.8 | Subdural hematoma, atrial fibrillation | Metastatic cancer of jejunum |
| Patients who discontinued because of miscellaneous causes (n = 2) | |||||||||||
| 1 | 55 | ND | 5.1 | UM | del17p + del11q + del13q | 6 | 27.4 | Dead | 1.1 | Therapy-related myelodysplasia, cytopenias | Died because of therapy-related myelodysplasia |
| 2 | 54 | + | 4.2 | UM | Del17p | 2 | 17 | Dead | 1.4 | Patient choice | No further treatment |
ara-C, rituximab; CVAD, cyclophosphamide, vincristine, adriamycin (doxorubicin) and dexamethasone; DIC, disseminated intravascular coagulation; M, mutated; MP, methylprednisolone; OFAR, oxaliplatin, fludarabine; R-MP, rituximab with methylprednisolone; UM, unmutated.
*
Chemoimmunotherapy - OFAR- Oxaliplatin, fludarabine, ara-C, Rituximab.
+
Patients who are alive.
†
Cause of sudden death in these 2 patients was unknown (autopsies not performed), 1 patient had no prior cardiac history and another had prior hypertension but no arrhythmias.
‡
Patients treated with ibrutinib and rituximab.