By Stefan O. Ciurea, MD from UCI Health
So I talked about a couple of abstracts from ASH presented ASH this year. And one of the most important probably was the late breaking abstract 4 with post transplantation Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil GVHD Prophylaxis randomized to tacrolimus (Tac) plus methotrexate (MTX) for patients with hematologic malignancies, ongoing transplantation with a reduced intensity condition regimen. This was a BMT CTN study 1703, and this study showed that GRFS GVHD-free relapse-free survival was significantly better. With Post-Transplant Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil as GVHD Prophylaxis compared with Tacrolimus and Methotrexate. It's important to note that this the results are better because of lower incidence of severe grade 3, 4 acute GVHD at relapse rate and overall survival was not significantly different. One limitation of this was the fact that ATG was not included in the control group for unrelated donors. And we use routinely ATG. And I'm concerned that if ATG would have been added, maybe maybe results would, could have been different.
Another interesting abstract was abstract 115 which evaluated outcomes of autologous transplant for high-risk myeloma based on presence of absence of plasma cells in the autographed, clonal plasma cells in the autografts. And it the NFG group showed nicely that presence of clonal plasma cells (CPC) in the autographed is associated with higher relapse rate and worse survival, both in patients, and again, in patients with high risk myeloma, but both in those that achieved VGPR and those who achieve less than VGPR response and conclusion of this study is that it's important to have a graph that is devoided of clonal plasma cells for patients with multiple myeloma.
Another interesting abstract was number 2101 allogeneic transplantation with high dose Post-Transplantation Cyclophosphamide (PTCy) for patients with acute lymphoblastic leukemia above age 55 years. This abstract showed that patients, older patients in remission should get a lower intensity condition regimen and patients had quite long-term disease free survival, 5 year relapse, 5 year relapse free survival and overall survival for patients in CR1 for B cell ALL was 61% and 64% respectively with lower incidence of relapse of only 16% even lower if patient patients had TKI maintenance.
Another interesting study was 2125 allogeneic stem cell transplantation for older patients with acute myeloid leukemia. This is a more an abstract retrospective study on more than a thousand patients from MD Anderson, older individuals about age 60 which showed that, older individuals can now expect higher CR rates or CR/CRi in without count recovery in the range of 70 plus percent similar to high intensity intensity treatment with hypomethylating agent or low intense steroid mass plus Venetoclax has clearly increased the CR rate, which enabled more patients to older individuals to get to transplant. And in the more recent cohort, approximately 50% of older individuals were able to get to transplant and patients who achieved disease control and went to transplant had better results.
Another interesting abstract was 2017 which showed that consolidation with allogeneic stem cell transplant for patients with a B cell ALL who undergo CAR T-cell therapy is associated with a better overall survival. And the, while this was a relatively small study the differences in survival was were quite impressive with a 1 year survival, 81% versus 16% for patients who did undergo transportation versus who did not. And of course, the failure for those who did not was because most of them relapsed.
Another interesting study that I reviewed was abstract 362, a phase 2 study with Posoleucel and off-the-shelf, multiverse specific T-cell therapy to prevent viral infections post-transplant. And this the product is an off the shelf, again, multiverse CTL product with against adenovirus, BKV virus, CMV, HVC, and JC Virus. Administered early after transfer within first 50 days between two weeks and about five weeks after allogeneic Trans. Patients get repeated infusions every two weeks. And the group showed that the incidence of severe, of clinically significant viral infections after transplant appears to be reduced. The number of patients was quite small and there was a concern I would say with about 30% of patient developing disease, grade 2 to 4. It is unclear from the abstract if this was the novel GVHD or patient who had GVHD 4 received this, although unlikely because the CTLs were administered fairly early after transplant. So it's likely that a proportion of patients develop acute Graft Vs. Host Disease grade 2 to 4.
Another abstract which I thought was interesting was 3371 evaluating outcomes of older individual receiving a transplant and the impact of developing of significant adverse effects and disability early after the transplant. And this was associated with significant decrease in survival, a higher early treatment rate mortality and lower survival in patients who develops either significant disability with impairment in function. ICU admission falls in the early post transplant post period usually first month. This this is again focused on transplantation for all the individuals, which makes. Think how, what ways to try to prevent this steep drop in disability free survival in these individuals. Early post transplant with reduced intensity conditioning better selection of patients geriatric assessment prior to transplant. Better. And and maybe other methods that one could employ to try to impact negative outcomes in this group. Early posttransplant.
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Maybe one last abstract is number 2058 using haploidentical transplants for patients receiving haploidentical transplants with grandchildren, compared with patients who receive haploidentical, older individuals who receive, haploidentical from children as donors, and in essence the the group showed that when they did a propensity score matching between patients who receive children and grandchildren. There were no significant differences in outcomes between the two groups, suggesting that grandchildren can potentially be used for older individuals in some cases because children cannot be used or are too old to be used for transplantation.
There were a few surprising things, one of which I would prefer to have in the late breaking abstract four, the randomized study post-site based GVHD prophylaxis with conventional GVHD prophylaxis. One would like to see how AG patients with related donors receive unrelated transplants with the addition of anti globin, which is fairly standard in many transplant centers.
And another surprising thing to me was that the multiple CTLs were associated. Some about 30 30% of the patients developed some significant Graft Versus Host disease, which which is a concern. I think these were the most surprising findings for me.
I think an important aspect is we're talking about transplant. There were a couple of abstracts at this ASH meeting and an important aspect was a transplantation for older individuals, and we are looking at an abstract in AML and again, acute lymphoblasts leukemia patients are transplanting older and older patients.
More older patients can be taken for transplants, and outcomes appear to have improved. We're learning how to do the transplant for these patients. And I am optimistic that this trend will continue in the future and we'll see more and more older individuals with, especially with acute leukemia reaching transplant not only because of better selection, patients improving the way we do the transplant, but also better. In the case of AML, additional Venetoclax appears to have made a big difference in terms of putting more patients in remission, which would enable more patients to get to a transplant and maybe even be cured of the disease.
Professor Stefan O. Ciurea is the director of the Hematopoietic Stem Cell Transplantation and Cellular Therapy Program at the Chao Family Comprehensive Cancer Center and a hematologist at UCI Health.
Romania's Grigore T. Popa University of Medicine and Pharmaceuticals in Iasi awarded Professor Ciurea his medical degree. He did his residency in internal medicine at UPMC Pinnacle Harrisburg in Harrisburg, Pennsylvania. Afterwards, he completed a fellowship in hematology-oncology at the University of Illinois College of Medicine in Chicago, followed by a fellowship in stem cell transplantation and cellular therapy at the University of Texas MD Anderson Cancer Center in Houston.
Before joining the Chao Family Comprehensive Cancer Center to direct its hematopoietic stem cell transplantation and cellular therapy program, Ciurea spent more than a decade on the faculty of the Department of Stem Cell Transplantation and Cellular Therapy at the MD Anderson Cancer Center.
Ciurea is the author of over 150 publications with peer review and over 10 book chapters. In addition, he has served as the lead investigator for numerous clinical trials, including investigator-initiated trials. He has been invited to present at over 50 meetings and conferences worldwide, including as the keynote speaker.