Multiply Relapsed Secondary CNS Non-Germinal Center Diffuse Large B-Cell Lymphoma Successfully Treated with CNS-Centric Therapy

Figures & data

Figure 1 MRI Imaging at Second Relapse. Contrast enhanced axial MRI showing infiltrative, multifocal, enhancing mass lesions with one of the larger components centered within the splenium of the corpus callosum.

Figure 2 Pathologic Evaluation of the Left Parietal Tumor. H&E x40 magnification shows large B cells (A). IHC x20 magnification shows that the neoplastic B-cells stained positive for CD20 (B), BCL6 (C), BCL2 (D), MUM1 (E) with a high MIB1 proliferation rate (F).

Abbreviations: H&E, haematoxylin and eosin; IHC, immunohistochemistry.

Figure 3 MRI Imaging Post-Treatment. (A and B) MRI after salvage therapy with near complete remission. (C) Repeat contrast enhanced MRI following day 100 work-up status post second ASCT shows complete remission.

Abbreviations: ASCT, autologous stem cell transplant; MRI, magnetic resonance imaging.

Table 1 Case Presentation Treatment Summary

Symptoms	Diagnosis	Induction Regimen	Consolidation Regimen	Maintenance
Presented to outside institution with abdominal pain/distension, fatigue, weight loss, night sweats	Stage IV NGC – DLBCL without BM or CNS involvement	6 cycles R-CHOP 4 doses of IT MTX	Autologous SCT with BEAM conditioning	None
Presented to outside institution with gait imbalance and blurred vision 1.5 years after autologous SCT	First CNS-only relapse of DLBCL	WBRT	None	None
Presented to our hospital with word finding difficulty and mental status changes 2 years post-WBRT	Second CNS- only relapse	Cycle 1: rituximab, HD-MTX, HiDAC. Cycles 2–4: rituximab plus HD-MTX and ibrutinib given rash thought to be due to HiDAC. Rash later determined due be due to acyclovir. Cycles 5–6: rituximab, HD-MTX, and HiDAC.	Second autologous SCT after conditioning with BCNU plus thiotepa	Ibrutinib

Abbreviations: BEAM, carmustine, etoposide, cytarabine, melphalan; BCNU, carmustine; CNS, central nervous system; DLBCL, diffuse large B-cell lymphoma; HD-MTX, high-dose methotrexate; HiDAC, high-dose cytarabine; IT MTX, intrathecal methotrexate; NGC, non-germinal center; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; SCT, stem cell transplant; WBRT, whole brain radiotherapy.

Table 2 Summary of Clinical Trials in SCNSL and Reported Outcomes

Clinical Trial	Phase	Type of SCNSL	Histology	Treatment	Total Accrual	CR	Survival
Ferreri AJM et al^5	2	Initial diagnosis and relapsed	DLBCL	Initial treatment (MATRIX x 3 cycles --> RICE x 3 cycles) followed by HD BCNU/TT and ASCT	79	55%	2Y PFS- 46%, 2Y OS- 46%
Ferreri AJM et al^4	2	Initial diagnosis and relapsed	DLBCL Blastoid MCL FL (Grade-3)	Initial treatment (R + HDMTX + HiDAC --> R-HD sequential chemotherapy with cyclophosphamide, Ara-C, and VP-16) followed by HD BCNU/TT and ASCT	38	63%	2Y EFS- 50%, 5Y OS- 41%
Korfel A et al^15	2	Relapsed	Aggressive lymphoma (Burkitt lymphoma and lymphoblastic lymphoma excluded)	Initial treatment (MTX/IFO/DEP--> Ara-C/TT/DEP) followed by HD BCNU/TT/VP-16 and ASCT	38	63%	2Y TTTF- 49%

Abbreviations: DLBCL, diffuse large b cell lymphoma; MCL, mantle cell lymphoma; FL, follicular lymphoma; MATRIX, High-dose methotrexate + high-dose Ara-C + thiotepa + Rituximab; RICE, Rituximab + ifosfamide + carboplatin + etoposide; BCNU, carmustine; TT, thiotepa; ASCT, autologous stem cell transplant; R, Rituximab; HDMTX, high-dose methotrexate; HiDAC, high-dose ara-c; VP-16, etoposide; MTX, methotrexate; IFO, ifosfamide; DEP, liposomal ara-c; CR, complete response; PFS, progression free survival; OS, overall survival; EFS, event free survival; TTTF, time to treatment failure.