Contributions
Abstract: PB1801
Type: Publication Only
Background
CNSi is extremely rare at MCL diagnosis but more frequent at relapse (4-8%) with poor prognosis (median survival <6 months). Leptomeningeal infiltration is more frequent than parenchymal disease.
Treatment includes CNS directed chemotherapy crossing the blood-brain barrier (BBB). Consolidation with HDT/ASCT can be considered for fit patients. Irradiation and palliative care are also options in relapsed/refractory (R/R) or unfit cases. Ibrutinib has shown significant single agent activity in R/R MCL.
Aims
We present two cases of MCL patients with secondary CNSi, successfully treated with Ibrutinib.
Methods
Case 1: A 58-year-old male was diagnosed with MCL stage IV, MIPI score high and ki-67 high (40%) in November 2011. He achieved CR with first line treatment (R-CHOP, 8 cycles followed by R maintenance). Three years after initial diagnosis (November 2014) he developed eye proptosis with pain and periorbital oedema. MRI scan showed intraorbital mass infiltrating the rectus muscles and extending into the maxillary sinuses. Further imaging only showed cervical lymphadenopathy. CSF examination was negative. He was treated with high dose Methotrexate and Cytarabine and achieved partial response. Additional treatment with Bendamustine-Rituximab (6 cycles, April 2015-September 2015) led to further radiological improvement.He suffered second disease recurrence in the same area 12 months later (September 2016). Whole body imaging with PET/CT scan revealed hypermetabolic foci inside the right frontal lobe with high uptake compared to brain parenchyma (SUV 16.7). CSF examination was negative. MRI confirmed the presence of intraparenchymal solid lesion. He was commenced on Ibrutinib 540 mg/d in November 2016. Follow-up imaging in March 2017 showed significant shrinkage of the intracranial tumor and complete response was seen in July 2017. Latest MRI imaging in January 2018 showed that he remains in continuous CR on ibrutinib treatment.
Results
Case 2: A 58 year-old male was diagnosed with stage IV, MIPI high MCL in November 2013. He achieved good PR after 6 cycles of R-CHOP. He was not considered eligible for HDT/autologous transplant consolidation. Six months later (October 2014) disease relapsed with Waldeyer ring involvement (confirmed by biopsy, Ki-67 75%) and CNSi (leptomeningeal disease only). He was treated with three cycles of HyperCVAD/MA and IT chemo to CR. In June 2015, there was systemic relapse with CNSi (leptomeningeal and parenchymal disease). He received salvage R-DHAP with responding systemic disease but only partial CNS response. There was CNS progression in October 2015, refractory to high dose Methotrexate. He was started on Ibrutininb 560 mg/day in November 2015. There was immediate response of CNS disease with CR on imaging 10 months later. Systemic disease remained in remission throughout, however he developed isolated CNS relapse in March 2017 (leptomeningeal and parenchymal). Disease was refractory to high dose Methotrexate but responded (PR) to Bendamustine, Cytarabine, Dexamethasone and Rituximab plus IT chemo (4 cycles). There was progression of CNS disease (parenchymal only) again in February 2018. He was started on Rituximab- Ifosfamide-Etoposide. Formal response assessment is pending.
Conclusion
Ibrutinib has been shown to rapidly cross the BBB and has been reported to have impressive clinical results in cases with CNS MCL relapse. Our experience described herein has also been positive. Salvage of MCL patients progressing on Ibrutinib treatment is difficult and outcomes are generally poor.
Session topic: 21. Aggressive Non-Hodgkin lymphoma - Clinical
Keyword(s): CNS lymphoma, ibrutinib, Mantle cell lymphoma
Abstract: PB1801
Type: Publication Only
Background
CNSi is extremely rare at MCL diagnosis but more frequent at relapse (4-8%) with poor prognosis (median survival <6 months). Leptomeningeal infiltration is more frequent than parenchymal disease.
Treatment includes CNS directed chemotherapy crossing the blood-brain barrier (BBB). Consolidation with HDT/ASCT can be considered for fit patients. Irradiation and palliative care are also options in relapsed/refractory (R/R) or unfit cases. Ibrutinib has shown significant single agent activity in R/R MCL.
Aims
We present two cases of MCL patients with secondary CNSi, successfully treated with Ibrutinib.
Methods
Case 1: A 58-year-old male was diagnosed with MCL stage IV, MIPI score high and ki-67 high (40%) in November 2011. He achieved CR with first line treatment (R-CHOP, 8 cycles followed by R maintenance). Three years after initial diagnosis (November 2014) he developed eye proptosis with pain and periorbital oedema. MRI scan showed intraorbital mass infiltrating the rectus muscles and extending into the maxillary sinuses. Further imaging only showed cervical lymphadenopathy. CSF examination was negative. He was treated with high dose Methotrexate and Cytarabine and achieved partial response. Additional treatment with Bendamustine-Rituximab (6 cycles, April 2015-September 2015) led to further radiological improvement.He suffered second disease recurrence in the same area 12 months later (September 2016). Whole body imaging with PET/CT scan revealed hypermetabolic foci inside the right frontal lobe with high uptake compared to brain parenchyma (SUV 16.7). CSF examination was negative. MRI confirmed the presence of intraparenchymal solid lesion. He was commenced on Ibrutinib 540 mg/d in November 2016. Follow-up imaging in March 2017 showed significant shrinkage of the intracranial tumor and complete response was seen in July 2017. Latest MRI imaging in January 2018 showed that he remains in continuous CR on ibrutinib treatment.
Results
Case 2: A 58 year-old male was diagnosed with stage IV, MIPI high MCL in November 2013. He achieved good PR after 6 cycles of R-CHOP. He was not considered eligible for HDT/autologous transplant consolidation. Six months later (October 2014) disease relapsed with Waldeyer ring involvement (confirmed by biopsy, Ki-67 75%) and CNSi (leptomeningeal disease only). He was treated with three cycles of HyperCVAD/MA and IT chemo to CR. In June 2015, there was systemic relapse with CNSi (leptomeningeal and parenchymal disease). He received salvage R-DHAP with responding systemic disease but only partial CNS response. There was CNS progression in October 2015, refractory to high dose Methotrexate. He was started on Ibrutininb 560 mg/day in November 2015. There was immediate response of CNS disease with CR on imaging 10 months later. Systemic disease remained in remission throughout, however he developed isolated CNS relapse in March 2017 (leptomeningeal and parenchymal). Disease was refractory to high dose Methotrexate but responded (PR) to Bendamustine, Cytarabine, Dexamethasone and Rituximab plus IT chemo (4 cycles). There was progression of CNS disease (parenchymal only) again in February 2018. He was started on Rituximab- Ifosfamide-Etoposide. Formal response assessment is pending.
Conclusion
Ibrutinib has been shown to rapidly cross the BBB and has been reported to have impressive clinical results in cases with CNS MCL relapse. Our experience described herein has also been positive. Salvage of MCL patients progressing on Ibrutinib treatment is difficult and outcomes are generally poor.
Session topic: 21. Aggressive Non-Hodgkin lymphoma - Clinical
Keyword(s): CNS lymphoma, ibrutinib, Mantle cell lymphoma