When given in combination with Kyprolis (carfilzomib), the investigative therapy Reolysin (pelareorep) elicits a strong inflammatory response — and promising clinical responses — in people with relapsed or refractory multiple myeloma, a Phase 1b trial shows.
The study’s findings were presented in a poster, titled “Oncolytic virus Pelareorep plus Carfilzomib & Dexamethasone phase I trial in Carfilzomib-refractory patients (NCI 9603): responses with cytokine storm,” at the recent 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.
The treatment candidate uses an engineered version of a harmless virus, called reovirus, that only infects and multiplies inside cancer cells. It causes their death and releases viral particles that infect nearby cancer cells. In addition to its cancer cell-killing ability, Reolysin also promotes inflammation, and helps recruiting immune cells to the tumor site, aiding the immune system to mount a response against the tumor.
Kyprolis, marketed by Amgen, is approved in the U.S. to treat people with myeloma who received at least one prior line of therapy. It belongs to the class of proteasome inhibitors, preventing cancer cells from destroying unnecessary or damaged proteins that become toxic when present in high levels inside cells.
When used with Reolysin, Kyprolis has been found to help the engineered virus enter, infect, and destroy cancer cells. The combination of both therapies is expected to help the immune system mount a response against the malignant cells that are infected with Reolysin.
A proof-of-concept, Phase 1b trial (NCT02101944) is investigating this combination for the treatment of myeloma patients who have relapsed or whose cancer is refractory, meaning it does not respond to therapy. The participants were treated with an immunomodulatory agent and a proteasome inhibitor, and failed to respond to Kyprolis.
All participants receive a combination of Reolysin and Kyprolis plus the corticosteroid dexamethasone. Treatment lasts until patients show signs of disease progression or unacceptable toxicity.
Findings from the first six participants show that Reolysin selectively targeted and multiplied inside myeloma cells. This was evidenced by its presence on bone marrow samples obtained on day 9 in all six patients.
The combination therapy triggered a strong inflammatory response, which was associated with clinically meaningful treatment responses.
Half of the patients achieved a partial response — or partial cancer elimination — and nearly all (83%) attained a state of disease stabilization or better. Disease progression was observed in only one of the participants.
“We are excited by the data showing an association between clinical and anti-tumor inflammatory response induced with pelareorep-carfilzomib treatment in this extremely difficult to treat patient population,” Douglas W. Sborov, MD, co-author of the poster presented at ASCO, said in a press release.
One of the patients who attained a partial response to treatment developed a cytokine storm — a severe immune reaction caused by the rapid and strong release of substances produced by activated immune T-cells. Despite responding initially to treatment with tocilizumab, which helps reduce these inflammatory reactions, the 58-year-old man ended up dying from hospital-acquired pneumonia, which was unrelated to the combination therapy.
“The induction of cytokine release syndrome, which can be effectively monitored and managed via treatment with tocilizumab and steroids, is particularly interesting as it highlights the ability of the treatment to induce robust immune cell activation and tumor lysis [destruction],” Sborov said.
“Taken together with earlier results from this study … the current data strongly support the potential of the ongoing trial investigating pelareorep, carfilzomib, and immune checkpoint inhibitor combination,” he added. “This ongoing study could ultimately result in the development of a new treatment option for this high-need indication.”
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