Consolidation therapy with or without autologous SCT

In a prospective, randomized trial published in abstract form, 346 patients with newly diagnosed primary CNS lymphoma (patients aged 65 years and younger and patients aged 66–70 years with a performance status of 2 or lower) underwent induction therapy with 4 cycles of rituximab, high-dose methotrexate, high-dose cytarabine, and thiotepa (IELSG43 [NCT02531841]). Eighty-six patients discontinued treatment due to toxicity or progression. Of the 260 patients who completed induction therapy, 229 patients were randomly assigned to receive either chemotherapy consolidation with rituximab, dexamethasone, etoposide, ifosfamide, and carboplatin (n = 115) or autologous SCT using BCNU and thiotepa (n = 114).[38][Level of evidence A1]

In a prospective, randomized trial published in abstract form, 346 patients with newly diagnosed primary CNS lymphoma (patients aged 65 years and younger and patients aged 66–70 years with a performance status of 2 or lower) underwent induction therapy with 4 cycles of rituximab, high-dose methotrexate, high-dose cytarabine, and thiotepa (IELSG43 [NCT02531841]). Eighty-six patients discontinued treatment due to toxicity or progression. Of the 260 patients who completed induction therapy, 229 patients were randomly assigned to receive either chemotherapy consolidation with rituximab, dexamethasone, etoposide, ifosfamide, and carboplatin (n = 115) or autologous SCT using BCNU and thiotepa (n = 114).[38][Level of evidence A1]

With a median follow-up of 44 months, the 3-year OS rate was 86% (78%–91%) for autologous SCT versus 71% (61%–78%) for chemotherapy alone (HR, 0.47; P = .01).[38][Level of evidence A1]

In a prospective, randomized trial published in abstract form, 346 patients with newly diagnosed primary CNS lymphoma (patients aged 65 years and younger and patients aged 66–70 years with a performance status of 2 or lower) underwent induction therapy with 4 cycles of rituximab, high-dose methotrexate, high-dose cytarabine, and thiotepa (IELSG43 [NCT02531841]). Eighty-six patients discontinued treatment due to toxicity or progression. Of the 260 patients who completed induction therapy, 229 patients were randomly assigned to receive either chemotherapy consolidation with rituximab, dexamethasone, etoposide, ifosfamide, and carboplatin (n = 115) or autologous SCT using BCNU and thiotepa (n = 114).[38][Level of evidence A1]

The 3-year PFS rate was 79% (71%–86%) for autologous SCT versus 53% (43%–62%) for chemotherapy alone.

In a prospective, randomized trial published in abstract form, 346 patients with newly diagnosed primary CNS lymphoma (patients aged 65 years and younger and patients aged 66–70 years with a performance status of 2 or lower) underwent induction therapy with 4 cycles of rituximab, high-dose methotrexate, high-dose cytarabine, and thiotepa (IELSG43 [NCT02531841]). Eighty-six patients discontinued treatment due to toxicity or progression. Of the 260 patients who completed induction therapy, 229 patients were randomly assigned to receive either chemotherapy consolidation with rituximab, dexamethasone, etoposide, ifosfamide, and carboplatin (n = 115) or autologous SCT using BCNU and thiotepa (n = 114).[38][Level of evidence A1]

There was no negative effect on neurocognitive function in either arm in the absence of progression.

In a prospective, randomized trial published in abstract form, 346 patients with newly diagnosed primary CNS lymphoma (patients aged 65 years and younger and patients aged 66–70 years with a performance status of 2 or lower) underwent induction therapy with 4 cycles of rituximab, high-dose methotrexate, high-dose cytarabine, and thiotepa (IELSG43 [NCT02531841]). Eighty-six patients discontinued treatment due to toxicity or progression. Of the 260 patients who completed induction therapy, 229 patients were randomly assigned to receive either chemotherapy consolidation with rituximab, dexamethasone, etoposide, ifosfamide, and carboplatin (n = 115) or autologous SCT using BCNU and thiotepa (n = 114).[38][Level of evidence A1]

This was the first randomized trial establishing a survival advantage for newly diagnosed patients receiving autologous SCT who are young enough and healthy enough to endure this aggressive approach.

In a prospective, randomized, phase II trial, 97 newly diagnosed patients receiving high-dose methotrexate combination therapy for induction were randomly assigned to receive WBRT at 40 Gy or autologous SCT.[34]

In a prospective, randomized, phase II trial, 97 newly diagnosed patients receiving high-dose methotrexate combination therapy for induction were randomly assigned to receive WBRT at 40 Gy or autologous SCT.[34]

With a median follow-up of 8 years, deterioration of balance was significantly greater for patients who received WBRT than for patients who received autologous SCT (52% vs. 10%, P ≤ .001). Worsening neurocognition was also greater for patients who received WBRT (64% vs. 13%, P < .001).

In a prospective, randomized, phase II trial, 97 newly diagnosed patients receiving high-dose methotrexate combination therapy for induction were randomly assigned to receive WBRT at 40 Gy or autologous SCT.[34]

The 8-year EFS rate was 67% for patients who received autologous SCT versus 39% for patients who received WBRT (HR, 0.13; P < .001). There was no difference in OS (69% for autologous SCT vs. 65% for WBRT).[34][Level of evidence B1]

In a prospective, randomized, phase II trial, 97 newly diagnosed patients receiving high-dose methotrexate combination therapy for induction were randomly assigned to receive WBRT at 40 Gy or autologous SCT.[34]

The authors concluded that 40 Gy WBRT should be avoided in first-line treatment because of its neurotoxicity and inferior efficacy.

A prospective, randomized, phase II trial included newly diagnosed patients aged 75 years and younger. Patients received intensive induction therapy with high-dose methotrexate at 8 g/m2 every 2 weeks, temozolomide, rituximab, and high-dose cytarabine. Patients were randomly assigned at the start of therapy to consolidation with thiotepa + BCNU conditioning with autologous SCT or nonmyeloablative therapy with high-dose cytarabine with a 46-hour infusion of etoposide (EA).[39]

A prospective, randomized, phase II trial included newly diagnosed patients aged 75 years and younger. Patients received intensive induction therapy with high-dose methotrexate at 8 g/m2 every 2 weeks, temozolomide, rituximab, and high-dose cytarabine. Patients were randomly assigned at the start of therapy to consolidation with thiotepa + BCNU conditioning with autologous SCT or nonmyeloablative therapy with high-dose cytarabine with a 46-hour infusion of etoposide (EA).[39]

With a median follow-up of 3.8 years, the median PFS was 6 years (95% CI, 3.9–not reached [NR]) for autologous SCT versus 2.4 years (95% CI, 0.6–NR) for EA (P = .02).[39][Level of evidence B1]

A prospective, randomized, phase II trial included newly diagnosed patients aged 75 years and younger. Patients received intensive induction therapy with high-dose methotrexate at 8 g/m2 every 2 weeks, temozolomide, rituximab, and high-dose cytarabine. Patients were randomly assigned at the start of therapy to consolidation with thiotepa + BCNU conditioning with autologous SCT or nonmyeloablative therapy with high-dose cytarabine with a 46-hour infusion of etoposide (EA).[39]

PFS from the time of consolidation was not statistically different (HR, 0.58; 95% CI, 0.25–1.36; P = .21).

A prospective, randomized, phase II trial included newly diagnosed patients aged 75 years and younger. Patients received intensive induction therapy with high-dose methotrexate at 8 g/m2 every 2 weeks, temozolomide, rituximab, and high-dose cytarabine. Patients were randomly assigned at the start of therapy to consolidation with thiotepa + BCNU conditioning with autologous SCT or nonmyeloablative therapy with high-dose cytarabine with a 46-hour infusion of etoposide (EA).[39]

There was no statistically significant difference in the 3-year OS rate: 83% (69%–91%) for autologous SCT and 72% (57%–82%) for EA.

A prospective, randomized, phase II trial included newly diagnosed patients aged 75 years and younger. Patients received intensive induction therapy with high-dose methotrexate at 8 g/m2 every 2 weeks, temozolomide, rituximab, and high-dose cytarabine. Patients were randomly assigned at the start of therapy to consolidation with thiotepa + BCNU conditioning with autologous SCT or nonmyeloablative therapy with high-dose cytarabine with a 46-hour infusion of etoposide (EA).[39]

This trial showed the limitations of induction therapy, which affected the impact of consolidation therapy.

Several phase II studies evaluated consolidation with intensive chemotherapy supported by autologous SCT.[19,20,23,40-43] This approach is appropriate for patients aged 80 years and under with few comorbidities, good performance status, and an adequate response to induction therapy.