POLIVY

First assessment.

Unfavourable opinion for reimbursement in combination with bendamustine and rituximab in the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who are not candidates for haematopoietic stem cell transplant.

Role in the care pathway?

The treatment of patients with diffuse large B-cell lymphoma (DLBCL) involves, as first-line therapy, a combination of chemotherapy with an anti-CD20 monoclonal antibody, i.e., the R-CHOP regimen. In the event of primary resistance or relapse, the treatment of choice is salvage chemotherapy followed by consolidation by autologous transplant in the event of chemotherapy-sensitive disease.

In patients not eligible for transplant due to an inadequate response to salvage chemotherapy or to the patient’s condition, treatment is based on immunochemotherapy with platinum and/or gemcitabine (in particular, the R-GemOx or R-DHAP regimens not followed by intensification and autologous transplant).

Relapsed or refractory patients following second-line salvage therapy may be able to have third-line chemotherapy. Treatment with CAR-T cells (axicabtagene ciloleucel or tisagenlecleucel) is recommended in patients whose life expectancy is compatible with the production timeframes. The following other options may be considered depending on the clinical situation:

• for relapsed patients (excluding refractory patients): additional intensive chemotherapy with the objective of performing allogeneic haematopoietic stem cell transplantation if the patient is eligible; where applicable an autologous transplant. An allogeneic transplant is generally considered in patients under the age of 70, in the absence of major comorbidities, in the presence of a donor (availability of a graft) and in the event of a complete response (or very good partial response) following the chemotherapy regimen;
• other chemotherapies,
• implementation of palliative care.

Role of the medicinal product in the care pathway

Considering:

• the methodological weakness of the clinical data obtained from a phase I/II multi-cohort trial including an exploratory randomised phase (with no superiority or non-inferiority hypothesis) performed with a liquid formulation of polatuzumab vedotin (without an MA) and in a limited number of patients who were heterogeneous in terms of their previous treatment line (min: 1; max: 7);
• the lack of clinical relevance of the comparator chosen for this randomised phase (rituximab + bendamustine - BR), little used in France, as well as that of the primary endpoint (complete response rate) in this clinical situation in which overall survival and quality of life data would have been more appropriate;
• the uncertainty with respect to this complete response rate, estimated to be 40% in patients treated with polatuzumab vedotin + BR compared to 17.5% in patients treated with BR, given the imbalances observed between these two groups, which may favour the polatuzumab vedotin + BR group (particularly with respect to the reasons for transplant ineligibility and disease prognostic factors);
• the lack of robust demonstration of an increase in overall survival compared to BR;
• the lack of quality of life data collected, which is regrettable since some of the adverse effects of polatuzumab vedotin could have an impact on this (in particular, peripheral neuropathy);
• uncertainties with the lyophilised form with the MA insofar as the data are very limited with this formulation (non-comparative cohort of 42 patients with efficacy results that appear to be inferior to those observed in the randomised phase with the liquid formulation);
• and the indirect comparisons (MAIC) submitted by the pharmaceutical company that do not enable quantification of the contribution of polatuzumab vedotin versus the reference treatments (R- GemOX-type polychemotherapy or CART-cells);

the Committee considers that POLIVY (polatuzumab vedotin) in combination with bendamustine and rituximab has no role in the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who are not candidates for haematopoietic stem cell transplant, in view of the alternatives and pending potential data from future clinical development.

-