The rates of survival and disease recurrence improved significantly when a personalized mRNA vaccine tailored to the patients’ tumor genetics was coupled with immunotherapy in those who had undergone surgery for high-risk melanoma, according to novel findings presented by Khattak et al at the 2023 ASCO Annual Meeting (Abstract LBA9503).
Background
"The current standard of care is immunotherapy using an antibody known as pembrolizumab," explained lead study author Adnan Khattak, MBBS, FRACP, PhD, Clinical Professor at Edith Cowan University, Director of the Cancer Clinical Trials Unity at the Fiona Stanley Hospital, and a medical oncologist at the Hollywood Private Hospital. "There are two main issues: first, despite having active immunotherapy for stage III melanoma, about half of patients will relapse at 5 years. [S]econdly, it's a very crude approach. [If] I treat 10 new [patients with] high-risk melanoma, I give them the same drug; it's not rocket science that it's going to work for some but not others, and some may see side effects and others may not,” he emphasized.
Although vaccines are typically associated with disease prevention, the novel mRNA vaccine in this study was used to treat patients who have already been diagnosed with melanoma.
Study Methods and Results
In the new study, the researchers first analyzed tumor tissue samples for up to 34 neoantigens, which are unique to a patient’s tumor. After identifying the neoantigens, the researchers then added them to an mRNA molecule and a subsequent vaccine in order to create personalized cancer treatments for each patient—incorporating the neoantigens most likely to develop an immune response to target the cancer cells.
After 18 months of follow-up, the researchers found that compared with those who only received immunotherapy, patients who received the mRNA vaccine and immunotherapy had a 78.6% rate of cancer-free survival vs 62.2%. Further, after 2 years of follow-up, only 22.4% of the patients who had received the treatment combination had died or experienced cancer recurrence vs 40%.
Overall, after an average of 2 years, patients who had received the vaccine saw a 44% lower risk of mortality or recurrence in the same area of the body and a 65% reduced risk of mortality or recurrence in a different area of the body. Additionally, the researchers noted that the mRNA vaccine appeared to be more effective after an extended period of time and required multiple doses.
“In this study, the survival rate between the two groups is the same after 40 weeks, so early relapses happen for both. Some patients have fairly resistant tumors that aren't going to respond to either of the treatments. But after the first 40 weeks, the patients have had two or three vaccine doses and the antitumor effect really kicks in,” Dr. Khattak revealed. “We see quite a significant proportion of patients relapsing after they finish pembrolizumab, whereas we're not seeing such late relapses in patients who have done the double treatment because in addition to pembrolizumab, the effect of the vaccine kicks in with a much stronger antitumor immune response,” he underscored.
The researchers also reported that they observed no significant increases in rates of adverse side effects among patients in the vaccine group.
Conclusions
"I would like to thank all my patients who took part in this research at a difficult point in their [lives]," Dr. Khattak stated. "This is the biggest trial to show treatment improves with an individualized approach—and I think research into personal cancer vaccines is going to increase dramatically after this positive study,” he highlighted.
Dr. Khattak and his colleagues are currently planning to initiate a new global trial of the mRNA vaccines that will include more participants, some with earlier stages of melanoma.
“[Patients with] stage II and stage III [melanoma] combined constitute quite a significant proportion of patients who could be potentially cured, rather than waiting for them to develop metastatic or advanced disease where most of them will not be curable,” Dr. Khattak continued.
If successful, the next trial could be the starting point of a new approach to cancer treatment beyond just melanoma. "This is going to be the stepping stone for a number of trials, because now they have expanded it into lung cancer, [renal carcinoma], and also into gastrointestinal cancers. This has the potential of becoming a new standard of care moving forward,” Dr. Khattak concluded.
Individuals who are interested in the details of the next trial can visit oneclinicalresearch.com.au.
Disclosure: For full disclosures of the study authors, visit meetings.asco.org.
