Melhem Solh, MD

Melhem Solh, MD, medical director for the Cellular Therapy Program at Northside Hospital, discusses what he is excited to see in the future for patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) that harbors a 

 gene mutation, gives his own recommendations to community oncologists who are treating patients with this disease.

Solh presented data on a group of patients who had AML or high-risk MDS with a 

 mutation who also underwent an allogeneic hematopoietic stem cell transplant at the 2022 Transplantation & Cellular Therapy Meetings

Data from his research showed that match-related donors were inferior to other groups of donors and about a third of patients with 

 mutations could be saved by getting a transplant. Among patients, the 3-year overall survival was 29%. Further research is warranted to gain more of an understanding on how to best treat this patient population.

With this specific population of patients, definitely the newer leukemia therapies that we have going on, another study for bispecifics, the natural killer cell treatment, and the chimeric antigen receptor T-cell therapy. It will be very interesting to see how we incorporate these types of therapy into transplant, pre or post, to help improve the outcome of this patient.

 It is very important with acute leukemias to be in touch with a tertiary center from the time of diagnosis, because with acute leukemia, getting these patients into donor typing and donor search and getting them to transplant in a timely fashion is very important. I can't stress that enough. Especially with a 

 del(17p), admission might be short, and you don't want to be delaying that. A quick referral to a transplant center is definitely helpful.

And 2, be sure that you are sending the markers of acute leukemia, as you're checking the chromosomes [and] next-generation sequencing to have all that data available at time of diagnosis, because that will help the transplant center make the best decisions and [know] how to proceed with those patients.

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Melhem Solh, MD, discusses the future for patients with myelodysplastic syndrome and acute myeloid leukemia that harbors a TP53 gene mutation, and gives his own recommendations to community oncologists who are treating patients with this disease.


Recommendations for Treating Patients With TP53-Mutated AML or MDS

Melhem M. Solh, MD, a blood and marrow transplant and leukemia program physician and medical director for the Cellular Therapy Program at Northside Hospital, discusses results of a study investigating allogeneic stem cell transplant (SCT) in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with a 

 mutation, previously presented at the 2022 Transplantation & Cellular Therapy Meetings.

Solh’s group at Northside Hospital looked at post-transplant outcomes for 30 patients in their SCT program, since 

 is associated with poor outcomes. When looking at outcomes, the 1-year overall survival (OS) rate was 62%, the 1-year disease-free survival (DFS) rate was 42%, 1-year rate of relapse was 51%, and the post-relapse survival rate was 19%. When looking at patients with both 

 mutations and deletion 17p (del[17p]), the 1-year OS rate was 73% and the DFS rate was 53%. The 3-year DFS rate was 27% for this subgroup.

The main reason for transplant failure was disease relapse, whether or not patients had both a 

 mutation and del(17p). When looking at factors related to outcomes, OS, DFS, and relapse rate appeared to be associated with disease risk. Notably, in this patient set, fully matched SCT recipients had poorer outcomes for relapse rate than those who received transplants from haploidentical or unrelated donors.

As we move into the outcomes for this patient population, the 1-year OS was 62%, DFS was 42%, relapse rate was 51%, and the post-relapse survival, patients who were alive post-relapse at 1 year, was 19%. Looking at the specific subgroups of patients who have a 

 mutation and del(17p), the numbers were similar with OS and DFS [at 73%] and 53%, [respectively] at 1 year, and that goes down to 27% at 3 years [for DFS]. The main reason for transplant failure was relapse in the 

When we looked at factors associated with outcomes and responses, we really didn't see [much]—No. 1, keep in mind, this is a small study, there are only 30 patients, so we may not have much power to detect any variability. But when you look at OS, the DRI or the Disease Risk Index was a main factor in picking [out] patients who did worse versus patients who did better. For DFS, it was the same story that disease risk was the main contributor to this. For relapse, we noticed 1 interesting finding, that patients who had a matched-sibling donors did poorly compared [with] patients who get either an unrelated-match donor or a haploidentical donor. Again, at relapse, the higher disease risk was correlated with a higher relapse. There was no difference in outcomes [whether] patients have del(17p) or if they did not have del(17p).

Melhem M. Solh, MD, discusses results of a study investigating allogeneic stem cell transplant in patients with myelodysplastic syndrome and acute myeloid leukemia with a TP53 mutation, previously presented at the 2022 Transplantation & Cellular Therapy Meetings.

Allogeneic SCT Shows Efficacy in TP53+ AML and MDS

Melhem Solh, MD, medical director for the Cellular Therapy Program at Northside Hospital, discusses his research on post-transplant outcomes of patients with TP53-mutant acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

Investigators, including Solh, examined 30 patients to evaluate overall survival (OS), relapse and non-relapse mortality, and disease-free survival (DFS) in patients with AML or MDS with a TP53 mutation and who had underwent an allogeneic hematopoietic stem cell transplant for this indication.

Due to the poor outcomes and survival rates seen for these patients, Sohl notes that the purpose of this trial is to further understand and improve options in this patient population.

In this presentation, we looked at a group of patients who have AML [or] high-risk MDS who underwent an allogeneic transplant in our program for this indication. We looked at several end points, including OS, DFS, relapse and non-relapse mortality.

The reason we're doing this is because patients who have TP53, which is a tumor suppressor gene on chromosome 17, tend to have very poor outcomes. If you look at patients with AML and MDS, their outcomes are usually very low and 1-year survival is very low. Even with transplant, historically, it's been reported to be less than 30%.

 Now, at this day and age, the improvement in attachment outcomes is newer medications that we can use to help get patients into deeper remission before transplant. That question [is], can we save some of these patients by taking them to an allogeneic transplant?

Melhem Solh, MD, discusses his research on post-transplant outcomes of patients with TP53-mutant acute myeloid leukemia and myelodysplastic syndrome.

Research Looks to Improve Outcomes in TP53-Mutant AML and MDS

Melhem Solh, MD, Northside Hospital, discusses how the standard of care for patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with the tumor protein 53 (

) gene mutation has changed over the past decade.

Research done by the Blood Marrow Transplant Program at Northside Hospital examined the outcomes of patients with AML and MDS who have a 

 gene mutation as well as the post-transplant outcomes of those patients as they tend to have very poor outcomes.

According to Solh, this patient population has been challenging as they have responded poorly to chemotherapy and often relapse quickly.

 This has been a very challenging population of patients because we know they've done poorly with chemotherapy. They tend to be refracted or have very quick relapses. If a patient has 

 deletion 17 AML, they are not eligible for transplant for 1 reason or the other, and they are not going to do well. Even with transplant, they still don't do too well compared to other subtypes of AML. The question is, using the drugs we have available now to put them in a deeper remission before transplant, would that translate into a better outcome?

 Now, unfortunately, we didn't have the amount of deep data on those patients and our analysis because some of them go back 6 or 7 years ago, before we're able to collect that type of data. That would be one question to answer. Do you really need to get as deep of a response to help improve, and would the transplant matter at that point in this specific subgroup? We know it matters in general to get somebody MRD negative.

 The other thing, using post-transplant maintenance, there's a tendency to try to put patients on a hypomethylating agent. There are studies going on to do a hypometh plus venetoclax [Venclexta] for high-risk patients, which I'd imagine this group would fall into. The answer for would make a difference in their outcomes is that we have to wait for the study to decide.

Melhem Solh, MD, discusses how the standard of care for patients with myelodysplastic syndrome and acute myeloid leukemia with the tumor protein 53 gene mutation has changed over the past decade. 

Melhem Solh, MD | Authors

Articles

Recommendations for Treating Patients With TP53-Mutated AML or MDS

Allogeneic SCT Shows Efficacy in TP53+ AML and MDS

Research Looks to Improve Outcomes in TP53-Mutant AML and MDS

Changes in the Management of TP53-Mutant AML