• There is no recommendation on treatment for CNS prophylaxis for patients on Polivy.
• In the Phase 3 POLARIX study, patients in both arms could receive IT CNS prophylaxis, but high-dose IV MTX was not allowed and was considered a new anti-lymphoma therapy.
• Published reports on the use of high-dose MTX for CNS prophylaxis in patients receiving Polivy are limited.

CNS=central nervous system

DLBCL=diffuse large B-cell lymphoma

HD-MTX=high-dose methotrexate

IT=intrathecal

IV=intravenous

LBCL=large B-cell lymphoma

MTX=methotrexate

R-CHP=rituximab, cyclophosphamide, doxorubicin, and prednisone

R-CHOP=rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone

R-HD-MTX=rituximab and high-dose methotrexate

There is no recommendation on treatment for CNS prophylaxis for patients on Polivy.[1]

The Phase 3 POLARIX study compared Polivy-R-CHP versus R-CHOP in patients with previously untreated DLBCL.[2]

In this study, patients in both arms could receive IT CNS prophylaxis, per institutional practice. High-dose IV MTX (e.g. 1 g/m² per cycle) was not allowed and was considered a new anti-lymphoma therapy.[3]

Patients who received CNS prophylaxis

In the Polivy-R-CHP group, 72 patients (16.4%) and in the R-CHOP group, 86 patients (19.6%) received CNS prophylaxis.[4] CNS prophylaxis included any IT administration of MTX, cytarabine, or corticosteroid.

Some patients in the Polivy-R-CHP arm received MTX as a concomitant treatment during the study treatment period or during the follow-up period. It was not specified how many of these patients received IT MTX for CNS prophylaxis.[5]

Published reports on the use of high-dose MTX for CNS prophylaxis in patients receiving Polivy are limited.

In the Phase 2 COALITION study of first-line glofitamab combined with Polivy-R-CHP (n=40) or R-CHOP (n=40) in patients with high-risk LBCL, IT or IV MTX, including HD-MTX (1-3 g/m² IV) given for 2 cycles 14 days apart, was permitted as CNS prophylaxis per institutional practice.[6] Overall, 11% of patients received IT MTX and 19% received IV MTX, at similar rates between treatment groups. Results were not stratified by MTX use. Of the 2 patients with progressive disease who relapsed with isolated CNS involvement, 1 had received CNS prophylaxis with 2 cycles of IV MTX 3 g/m². The patient’s treatment assignment was not reported.

In a retrospective study of Polivy-R-CHP (n=356) versus R-CHOP (n=740) in patients with untreated DLBCL,19 patients (5.4%) and 34 patients (4.6%), respectively, received HD-MTX, and 72 (20.2%) and 53 (7.2%), respectively, received IT chemotherapy (regimen not reported).7 Results, including rates of CNS relapse, were not stratified by HD-MTX or IT chemotherapy use.

Ongoing JCOG2201/PREMIER Study

The Phase 3, multicenter, randomised, controlled JCOG2201/PREMIER trial is evaluating Polivy-R-CHP plus CNS prophylaxis with IT chemotherapy, with and without IV R-HD-MTX, in patients with untreated DLBCL at high risk for CNS relapse.[8]

IT chemotherapy

• consists of MTX 15 mg, cytarabine 40mg, and prednisolone 10 mg; and
• is administered prior to Polivy-R-CHP during Cycles 2, 3, 5, and 6.[8]

R-HD-MTX

• consists of 2 cycles of IV rituximab 375 mg/m2 on Day 1 and IV MTX 3.5 g/m2 (2 g/m2 if ≥70 years of age) on Day 2, every 2 weeks, and
• is administered between the first 3 cycles and the last 3 cycles of Polivy-R-CHP.[8]

Patients who receive HD-MTX, also receive leucovorin to reduce HD-MTX toxicity.[8]

The trial is registered in the Japan Registry of Clinical Trials.[8] Study status updates may be found at https://jrct.mhlw.go.jp/latest-detail/jRCTs031230505.

1. Roche Internal Regulatory Report (Polivy CDS v6.0).
2. Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. N Engl J Med. 2022;386(4):351-363. doi:10.1056/NEJMoa2115304
3. Protocol for Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. Accessed July 25, 2023. https://www.nejm.org/doi/suppl/10.1056/NEJMoa2115304/suppl_file/nejmoa2115304_protocol.pdf.
4. The New England Journal of Medicine. Table S2 in Supplementary Appendix of Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. January 27, 2023. Accessed July 25, 2023. https://www.nejm.org/doi/suppl/10.1056/NEJMoa2115304/suppl_file/nejmoa2115304_appendix.pdf.
5. Roche Internal Clinical Report (POLARIX CSR).
6. Minson A, Verner E, Giri P, et al. Glofitamab Combined With Pola-R-CHP or R-CHOP as First Therapy in Younger Patients With High-Risk Large B-Cell Lymphoma: Results From the COALITION Study. J Clin Oncol Off J Am Soc Clin Oncol. 2025;43(23):2595-2605. doi:10.1200/JCO-25-00481
7. Terao T, Yoshida I, Kobayashi H, et al. Efficacy and relapse profiles of Pola-R-CHP versus R-CHOP in previously untreated diffuse large B-cell lymphoma: A multicentre real-world study. Br J Haematol. 2026;208(2):554-563. doi:10.1111/bjh.70280
8. Sano Y, Miyazaki K, Yamaguchi M, et al. Protocol digest of a randomized phase III study of pola-R-CHP/high-dose methotrexate/IT vs. pola-R-CHP/IT for newly diagnosed diffuse large B-cell lymphoma with high risk of central nervous system relapse: JCOG2201 (PREMIER). Jpn J Clin Oncol. 2026;56(3):358-363. doi:10.1093/jjco/hyaf202