From the Guidelines
Polatuzumab vedotin should not be used as a first-line treatment for HIV-associated diffuse large B-cell lymphoma (DLBCL) due to the lack of data in this patient population, and R-CHOP remains the standard of care. The use of polatuzumab vedotin in combination with rituximab-cyclophosphamide-edoxorubicine-prednisone (Pola-R-CHP) has shown improved progression-free survival (PFS) in patients without HIV 1, but its efficacy and safety in HIV-positive patients with DLBCL are unknown.
Key Considerations
- The current standard treatment for HIV-associated DLBCL is R-CHOP, which should be administered using the standard schedule of six cycles given every 3 weeks 1.
- Alternative regimens such as DA-R-EPOCH and R-CDE have shown comparable outcomes to R-CHOP in some studies, but their use in HIV-positive patients requires further investigation 1.
- CNS prophylaxis with intrathecal (IT) MTX with or without Ara-C or intravenous (i.v.) MTX may be considered in patients with high-risk features, using the same criteria as those used in people without HIV 1.
Treatment Approach
- R-CHOP should be the first-line treatment for HIV-associated DLBCL, given its established efficacy and safety in this patient population 1.
- The use of polatuzumab vedotin and other alternative regimens should be considered in the context of clinical trials or after failure of standard therapy, due to the lack of data on their efficacy and safety in HIV-positive patients 1.
From the FDA Drug Label
12 CLINICAL PHARMACOLOGY
- 1 Mechanism of Action Polatuzumab vedotin-piiq is a CD79b-directed antibody-drug conjugate with activity against dividing B cells. The small molecule, MMAE, is an anti-mitotic agent covalently attached to the antibody via a cleavable linker. The monoclonal antibody binds to CD79b, a B-cell specific surface protein, which is a component of the B-cell receptor Upon binding CD79b, polatuzumab vedotin-piiq is internalized, and the linker is cleaved by lysosomal proteases to enable intracellular delivery of MMAE. MMAE binds to microtubules and kills dividing cells by inhibiting cell division and inducing apoptosis.
Polatuzumab vedotin-piiq is a CD79b-directed antibody-drug conjugate that works by binding to CD79b, a B-cell specific surface protein, and delivering the anti-mitotic agent MMAE to dividing B cells, ultimately killing them by inhibiting cell division and inducing apoptosis 2.
- The mechanism of action involves the binding of the monoclonal antibody to CD79b, internalization, and cleavage of the linker to deliver MMAE.
- MMAE then binds to microtubules and kills dividing cells.
- The drug has shown activity against dividing B cells.
From the Research
Overview of Polatuzumab
- Polatuzumab vedotin is a CD79b-targeted antibody-drug conjugate that delivers a potent antimitotic agent to B cells 3, 4.
- It has been studied in combination with bendamustine and rituximab for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) 3, 4, 5, 6.
Efficacy of Polatuzumab
- The overall response rate (ORR) of polatuzumab vedotin in combination with bendamustine and rituximab was 42.9% at the end of treatment, with a complete response rate (CRR) of 34.3% 3.
- A systematic review and meta-analysis found a significant ORR of 52.6%, CR of 34.3%, and PR of 15.5% in patients with relapsed or refractory DLBCL treated with polatuzumab vedotin plus bendamustine and rituximab 5.
- Real-world data from Turkey showed an overall response rate of 47.9%, including a 32.4% complete response rate, in patients treated with polatuzumab vedotin, rituximab, and bendamustine 6.
Safety of Polatuzumab
- The most common grade 3-4 adverse events associated with polatuzumab vedotin plus bendamustine and rituximab were hematological, including anemia, neutropenia, and thrombocytopenia 3, 5, 6.
- Grade 1-2 peripheral neuropathy was reported in 14% of patients, with no grade 3 or higher peripheral neuropathy events observed 3.
- Real-world data from Turkey showed that grade 3-4 neutropenia and thrombocytopenia were the most common hematological toxicities associated with polatuzumab vedotin, rituximab, and bendamustine 6.
Ongoing Research and Future Directions
- Polatuzumab vedotin is being studied in a randomized trial in the front-line setting in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) 4.
- Further high-quality randomized trials are needed to better understand and evaluate the efficacy and safety of polatuzumab vedotin plus bendamustine and rituximab in patients with relapsed or refractory DLBCL 5.