Considerations for retreatment with Polivy:

• Dedicated clinical studies evaluating the risk-benefit balance of retreatment with Polivy have not been conducted.

• In a trial amongst patients with R/R aggressive LBCL, two patients were retreated with Polivy and mosunetuzumab. One patient experienced a CR and one a PR for six months before progression.

• In vitro, Polivy-resistant cells were used to assess the combinaed efficacy of Polivy and rituximab. The authors concluded that retreatment with this combination could be a therapeutic option for Polivy-resistant tumors.

• In a retrospective study amongst patients with R/R B-cell lymphomas, a patient receiving bridging therapy was retreated with five cycles of Polivy-BR after failure of CAR T-cell therapy. The patient achieved a PR, enabling them to undergo consolidative alloHCT.

• Polivy dosing beyond six cycles was permitted in phase 1 and 2 trials, but was capped to six or eight cycles in subsequent trials due to the cumulative nature of PN.

• A time-to-event analysis of Polivy-induced PN, suggested that capping Polivy treatment duration to six to eight cycles at doses of 1.8–2.4 mg/kg would result in PN incidences comparable to other antimicrotubule agents.

A phase 1b/2 trial evaluated mosunetuzumab in combination with Polivy in R/R aggressive LBCL.[1] Patients with an initial CR, who subsequently progressed, were permitted to receive retreatment with Polivy and mosunetuzumab. Two patients were retreated this way; one experienced another CR and one a PR. Both responses lasted more than six months before progression. Additionally, five patients were retreated with Polivy in combination with other anti-lymphoma therapies, however retreatment outcomes for these patients were not reported.

In vitro, Polivy resistant cells were used to assess the combined efficacy of Polivy and rituximab.[2] Pretreatment with Polivy enhanced rituximab-induced CDC sensitivity in two Polivy-resistant cells with distinct mechanisms of resistance: increased MDR1 or decreased Bim expression. Combination treatment of Polivy with rituximab enhanced antitumor activity in STR-428-Pola-R xenografted mice. The authors concluded that retreatment with Polivy in combination with rituximab could be a therapeutic option in patients with Polivy-resistant tumors.

A retrospective multicenter study evaluated Polivy as a salvage and bridging treatment in adults with R/R LBCL who had failed at least two lines of therapy.[3] A patient receving bridging therapy was retreated with Polivy after failure of CAR T-cell therapy. Patient initially received three cycles of Polivy-BR, achieved a PR, started CAR T-cell therapy but relapsed after two months. The patient was retreated with five cycles of Polivy-BR and achieved a PR again, enabling him to undergo consolidative alloHCT. 

In Phase 1 and 2 trials with Polivy in DLBCL, dosing of Polivy beyond six cycles was permitted.[4,5] However, ongoing and future trials are limited to six or eight Polivy cycles because of the

• apparent cumulative nature of peripheral neuropathy leading to study treatment discontinuation, and

• supportive exposure-response and time-to-event analysis.

A time-to-event analysis concluded that the risk of grade ≥2 PN increased with increasing exposure to antibody‐conjugated MMAE and treatment duration.[6] The model‐estimated PN incidence suggested that capping treatment duration to six to eight Polivy cycles at doses of 1.8–2.4 mg/kg would result in PN incidences comparable to other antimicrotubule agents.

1. Budde LE, Olszewski AJ, Assouline S, et al. Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. Nat Med 2024;30:229-239. https://www.ncbi.nlm.nih.gov/pubmed/38072960
2. Kawasaki N, Tomita M, Yamashita-Kashima Y, et al. Efficacy of retreatment with polatuzumab vedotin in combination with rituximab in polatuzumab vedotin-resistant DLBCL models. Leuk Lymphoma 2023;64:1938-1948. https://www.ncbi.nlm.nih.gov/pubmed/37548343
3. Liebers N, Duell J, Fitzgerald D, et al. Polatuzumab vedotin as a salvage and bridging treatment in relapsed or refractory large B-cell lymphomas. Blood Adv 2021;5:2707-2716. https://www.ncbi.nlm.nih.gov/pubmed/34196677
4. Palanca-Wessels MC, Czuczman M, Salles G, et al. Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study. Lancet Oncol 2015;16:704-15. https://www.ncbi.nlm.nih.gov/pubmed/25925619
5. Morschhauser F, Flinn IW, Advani R, et al. Polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed or refractory non-Hodgkin lymphoma: final results from a phase 2 randomised study (ROMULUS). Lancet Haematol 2019;6:e254-e265. https://www.ncbi.nlm.nih.gov/pubmed/30935953
6. Lu D, Gillespie WR, Girish S, et al. Time-to-Event Analysis of Polatuzumab Vedotin-Induced Peripheral Neuropathy to Assist in the Comparison of Clinical Dosing Regimens. CPT Pharmacometrics Syst Pharmacol 2017;6:401-408. https://www.ncbi.nlm.nih.gov/pubmed/28544534