Photo from Penn Medicine
Infusions of modified autologous T cells may improve responses in multiple myeloma (MM) patients undergoing autologous stem cell transplant (auto-SCT), according to research published in Nature Medicine.
Researchers said patients who received the T cells—which were engineered to express an affinity-enhanced T-cell receptor (TCR)—after auto-SCT had a better response rate than is expected for MM patients undergoing auto-SCT. At day 100, the overall response rate was 90%.
The researchers also said the T cells were safe. There were no treatment-related deaths, and all 7 serious adverse events were resolved.
“This study shows us that these TCR-specific T cells are safe and feasible . . . , but it also revealed encouraging antitumor activity and showed impressive, durable T-cell persistence,” said study author Carl June, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.
The research was a collaboration between the University of Maryland School of Medicine, the Perelman School of Medicine, and Adaptimmune, a clinical stage biopharmaceutical company that owns the core TCR technology and funded the study.
The study included 20 evaluable patients with advanced MM. They received an average of 2.4 billion autologous T cells 2 days after undergoing auto-SCT.
The T cells were engineered to express an affinity-enhanced TCR recognizing a naturally processed peptide shared by the cancer-testis antigens NY-ESO-1 and LAGE-1. Up to 60% of advanced myelomas have been reported to express NY-ESO-1 and/or LAGE-1, which is correlated with tumor proliferation and poorer outcomes.
Response and survival
“The majority of patients who participated in this trial had a meaningful degree of clinical benefit,” said study author Aaron P. Rapoport, MD, of the University of Maryland School of Medicine in Baltimore.
“Even patients who later relapsed after achieving a complete response to treatment or didn’t have a complete response had periods of disease control that I believe they would not have otherwise experienced. Some patients are still in remission after nearly 3 years.”
Treatment responses were as follows:
| Outcome | Prior
to infusion |
Day
42 |
Day
100 |
Day
180 |
|---|---|---|---|---|
| Complete
response (CR) |
1 | 2 | ||
| Stringent
CR |
1 | 2 | 2 | |
| Near
CR |
1 | 6 | 11 | 8 |
| Very
good partial response |
2 | 7 | 2 | 2 |
| Partial
response |
6 | 4 | 2 | 1 |
| Stable
disease |
6 | 2 | 1 | 1 |
| Progressive
disease |
5 | 1 | 3 |
A subset of patients received lenalidomide maintenance after day 100, and 1 patient had died by the 180-day mark, as a result of disease progression.
The researchers noted that relapse was associated with a loss of the engineered T cells, which suggests methods for sustaining long-term persistence of the cells could improve outcomes.
At a median follow up of 21.1 months, 75% of patients were still alive, 50% were progression-free, and 25% had died after disease progression.
At a median follow up of 30.1 months, the median progression-free survival was 19.1 months, and the median overall survival was 32.1 months.
Adverse events
There were no treatment-related deaths, and all 7 serious adverse events were resolved. The serious events included grade 3 gastrointestinal graft-vs-host disease (GVHD), grade 3 hypoxia, grade 3 dehydration, grade 4 neutropenia, grade 4 hyponatremia, grade 4 hypotension, and grade 4 pancytopenia.
There were 17 adverse events that were considered probably related to treatment. These were gastrointestinal GVHD (3 grade 3), skin GVHD (2 grade 2), fatigue (1 grade 1), fever (2 grade 1-2), rash (3 grade 1-3), diarrhea (2 grade 1-2), sinus tachycardia (1 grade 1), injection site reaction/extravasation changes (1 grade 1), weakness (1 grade 1), and hypotension (1 grade 3).
“This study suggests that treatment with engineered T cells is not only safe but of potential clinical benefit to patients with certain types of aggressive multiple myeloma,” Dr Rapoport said. “Our findings provide a strong foundation for further research in the field of cellular immunotherapy for myeloma to help achieve even better results for our patients.”
