The European Commission conditionally approved polatuzumab vedotin (Polivy®; Genentech/Roche), an antibody-drug conjugate, in combination with bendamustine + rituximab (MabThera®; Roche for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), who are not candidates for a hematopoietic stem cell transplant.
The novel therapeutic agent is a first-in-class anti-CD79b ADC. CD79b (B-cell antigen receptor complex-associated protein beta chain) is a protein is expressed specifically in the majority of B-cells (an immune cell impacted in some types of non-Hodgkin lymphoma (NHL), making it a promising target for the development of new therapies.
Limited treatment options
For patients with refractory to initial treatment or relapse after an initial response, only a small percentage of patients with DLBCL will experience prolonged disease-free survival with salvage chemo-immunotherapy alone.
While chemotherapy followed by stem cell transplantation can be used to treat patients with DLBCL whose disease is refractory or relapsed following initial chemotherapy, treatment options remain limited.
“People with relapsed or refractory diffuse large B-cell lymphoma have limited treatment options – especially those who are not candidates for hematopoietic stem cell transplant,” explained Levi Garraway, MD, Ph.D, Roche’s Chief Medical Officer and Head of Global Product Development.
Polatuzumab vedotin offers patients a new, much needed, treatment option for this aggressive disease.
“With this approval, people in the EU with relapsed or refractory diffuse large B-cell lymphoma will have the opportunity to benefit from this new polatuzumab vedotin combination,” Garraway further noted.
“For patients battling this aggressive disease, the prognosis is poor and few treatments are available. We are proud to bring this first-in-class treatment option to those who need it most,” he added.
Antibody-drug conjugate or ADCs are highly targeted biopharmaceutical drugs that combine monoclonal antibodies specific to surface antigens present on particular tumor cells with highly potent anti-cancer agents linked via a chemical linker.
With seven approved drugs on the market, including polatuzumab vedotin, ADCs have become a powerful class of therapeutic agents in oncology and hematology.
Polatuzumab vedotin consists of a humanized anti-CD79b antibody that is conjugated to the dolastatin analog monomethyl auristatin E (MMAE) through engineered cysteines (THIOMABs) by a protease cleavable linker (valine–citrulline; maleimidocaproylvaline-citrulline-p-aminobenzoyloxycarbonyl or MC-VC-PABC), utilizing proprietary technology developed by Seattle Genetics.
Mechanism of Action
Polatuzumab vedotin binds to CD79b and destroys these B-cells through the delivery of an anti-cancer agent, which is thought to minimize the effects on normal cells.
The drug is marketed in the United States by Genentech as polatuzumab vedotin-piiq, with piiq as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the US Food and Drug Administration (FDA)
As part of their approval process, the European regulators reviewed the results from the phase Ib/II GO29365 study, the first and only clinical trial to show higher response rates and improved overall survival (OS) compared to bendamustine + rituximab in people with R/R DLBCL who are not candidates for a hematopoietic stem cell transplant. Results of the study showed that 40% of people treated with polatuzumab vedotin in combination with bendamustine + rituximab achieved a complete response (n=16/40), meaning no cancer could be detected at the time of assessment, compared to 17.5% (n=7/40) with bendamustine + rituximab alone. Complete response rates were assessed by an independent review committee.
The study also showed that polatuzumab vedotin plus bendamustine + rituximab more than doubled OS, with a median OS of 12.4 months in the polatuzumab vedotin arm, versus 4.7 months in the BR alone arm (HR=0.42). The most commonly reported adverse events in people treated with polatuzumab vedotin in combination with bendamustine + rituximab include anaemia, thrombocytopenia, neutropenia, fatigue, diarrhoea, nausea, and pyrexia.
A Study of Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab or Obinutuzumab Plus Bendamustine in Participants With Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma – NCT02257567
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 What are antibody-drug conjugates? ADC Review | Journal of Antibody-drug Conjugates. Online. Last accesses January 19, 2020.