Figure 3.
Differential outcomes in newly diagnosed PCNSL according to genetic risk groups. (A) Diagram of progression rate in high-risk and low-risk genetic subgroups of patients. Left panel: high-risk group (n = 50 patients, with the high-risk genetic aberrations involving at least 1 of the 4 loci: 6p CN-LOH/6p21.3 HD, BTG1, ETV6, and TP53 muts; 64% total patients): 17 patients progressed during induction MTR (34%), 24 patients whose disease responded to MTR proceeded to dose-intensive consolidation (22 received EA, 2 received myeloablative consolidation with BCNU/Thiotepa); 8 of 24 patients progressed (33%), including 1 of the 2 patients that received autologous stem cell transplantation; 4 patients received no further therapy after induction and were observed; each of these 4 patients progressed. Five patients received maintenance therapy after induction (4 with lenalidomide and 1 with rituximab); 3 of these patients progressed (1 patient started lenalidomide shortly after MTR and progressed within the first 6 months of treatment). Overall, 64% of the patients in the high-risk genetic subgroup have progressed, and all 15 deaths occurred in this group. Right panel: low-risk group (n = 28 patients, no high-risk aberrations at the 4 loci; 36% total patients). None of these patients progressed during the first 6 months of induction therapy with MTR. Overall, 20 of these patients proceeded to consolidation (19 received EA and 1 received myeloablative consolidation with BCNU/Thiotepa); of these, only 1 has progressed (5%). Five patients received no therapy after induction; only 2 of these patients have progressed. Three patients received maintenance therapy after induction (each received lenalidomide); none of these patients have progressed. Overall, 11% of patients in the low-risk genetic subgroup have progressed and none have died. (B) Kaplan-Meier estimates of the survival curves for PFS for the genetic high-risk group patients who received consolidation (n = 24), and (C) for the genetic low-risk group patients who received consolidation (n = 20). Among those patients who received consolidation therapy, the high-risk genetic subgroup has had 8 progression events (33%) with median PFS 4.8 years, whereas the low-risk genetic subgroup has had only 1 progression event (5%) with median PFS not reached.

Differential outcomes in newly diagnosed PCNSL according to genetic risk groups. (A) Diagram of progression rate in high-risk and low-risk genetic subgroups of patients. Left panel: high-risk group (n = 50 patients, with the high-risk genetic aberrations involving at least 1 of the 4 loci: 6p CN-LOH/6p21.3 HD, BTG1, ETV6, and TP53 muts; 64% total patients): 17 patients progressed during induction MTR (34%), 24 patients whose disease responded to MTR proceeded to dose-intensive consolidation (22 received EA, 2 received myeloablative consolidation with BCNU/Thiotepa); 8 of 24 patients progressed (33%), including 1 of the 2 patients that received autologous stem cell transplantation; 4 patients received no further therapy after induction and were observed; each of these 4 patients progressed. Five patients received maintenance therapy after induction (4 with lenalidomide and 1 with rituximab); 3 of these patients progressed (1 patient started lenalidomide shortly after MTR and progressed within the first 6 months of treatment). Overall, 64% of the patients in the high-risk genetic subgroup have progressed, and all 15 deaths occurred in this group. Right panel: low-risk group (n = 28 patients, no high-risk aberrations at the 4 loci; 36% total patients). None of these patients progressed during the first 6 months of induction therapy with MTR. Overall, 20 of these patients proceeded to consolidation (19 received EA and 1 received myeloablative consolidation with BCNU/Thiotepa); of these, only 1 has progressed (5%). Five patients received no therapy after induction; only 2 of these patients have progressed. Three patients received maintenance therapy after induction (each received lenalidomide); none of these patients have progressed. Overall, 11% of patients in the low-risk genetic subgroup have progressed and none have died. (B) Kaplan-Meier estimates of the survival curves for PFS for the genetic high-risk group patients who received consolidation (n = 24), and (C) for the genetic low-risk group patients who received consolidation (n = 20). Among those patients who received consolidation therapy, the high-risk genetic subgroup has had 8 progression events (33%) with median PFS 4.8 years, whereas the low-risk genetic subgroup has had only 1 progression event (5%) with median PFS not reached.

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