POLATUZUMAB VEDOTIN-PIIQ INJ,LYPHL

Clinical Criteria Summary

Absolute Neutrophil Count < 1000/µL
Platelet count < 75,000/µL (if no bone marrow involvement)
Moderate or severe hepatic impairment [Total bilirubin > 1.5 times upper limit of normal (unless Gilbert’s syndrome or liver involvement)]
Creatinine clearance < 40 ml/min
Baseline peripheral neuropathy > Grade 2
Chronic or unresolved infection
Unmanageable drug-drug interaction
Pregnancy
Lactating

Care provided by a VA/VA Community Care oncology or hematology provider
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Goals of care and role of Palliative Care consult have been discussed and documented

In combination with rituximab, cyclophosphamide, doxorubicin and prednisone (R-CHP) for previously untreated diffuse large B-cell lymphoma with International Prognostic Index score 2-5
In combination with bendamustine and rituximab (BR) for relapsed or refractory, diffuse large B-cell lymphoma previously treated with > 2 prior lines of therapy

For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 5 months after stopping treatment.

Previously untreated diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL) with an International Prognostic Index (IPI) score > 2, in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (R-CHP).
Relapsed or refractory DLBCL after at least 2 prior lines of therapy (LOT), in combination with bendamustine and a rituximab product.

Untreated DLBCL: IPI score 2-5; ECOG performance status 0-2.
Excluded populations: Transformed lymphoma, primary mediastinal large B-cell lymphoma, known CNS lymphoma, peripheral neuropathy (grade > 2).
Relapsed/refractory DLBCL: Transplant-ineligible patients; ineligible for hematopoietic stem cell transplant (HSCT) due to age (40%), insufficient response to salvage therapy (26%), or prior HSCT failure (20%).
Populations not demonstrating clear benefit with polatuzumab-R-CHP: Age < 60 years, germinal-center B-cell-like subtype of DLBCL, bulky (>7 cm) disease, lower IPI score.

First-line Advanced stage (III, IV), ECOG 0-2, IPI 2-5, non-germinal center origin: Pola-R-CHP.
Relapsed DLBCL: Pola-BR in patients who are not candidates for autologous stem cell transplant (ASCT) or CAR T-cell therapy.

Recommended as bridging therapy to CAR T-cell therapy during the CAR T-cell manufacture period.
Bridging therapy with polatuzumab ± rituximab ± bendamustine is category 2A per NCCN guidelines.
Must be administered only after leukapheresis, as it may impact cell collection.
Recommendations are per the cellular therapy team.

Polatuzumab: 1.8 mg/kg IV every 21 days for 6 cycles.
Administered in combination with either R-CHP or bendamustine + rituximab (BR) per specified cycle schedules.

Peripheral neuropathy: Monitor for new or worsening symptoms; onset typically ~2 months.
Infusion-related reactions: Administer antihistamine and antipyretic prior to administration; monitor during infusion.
Myelosuppression: Primary prophylaxis with G-CSF recommended for neutropenia due to Pola-R-CHP; consider for Pola-BR. Monitor for neutropenia, thrombocytopenia, and anemia.
Infections: Administer prophylaxis for Pneumocystis jiroveci pneumonia and herpesvirus; monitor for serious and opportunistic infections.
Progressive multifocal leukoencephalopathy (PML): Monitor for new or worsening neurologic, cognitive symptoms, or behavioral changes.
Tumor lysis syndrome: Monitor closely in patients with high tumor burden; provide prophylaxis to those at risk.
Hepatotoxicity: Monitor liver function tests and bilirubin; use caution in patients with pre-existing liver disease, elevated baseline liver enzymes, or concomitant medications.
Embryo-fetal toxicity: Advise effective contraception due to potential fetal harm.