Hi, I'm Mikkael Sekeres. I'm chief of the Division of Hematology and Professor of Medicine at the Sylvester Cancer Center, the University of Miami. I'm also chair of the Committee on Communications at the American Society of Hematology. My clinical and research disease specialties are myeloid malignancies, specifically myelodysplastic syndrome and acute myeloid leukemia.
There was a great study that was one of the plenary presentations that added blinatumomab to chemotherapy in children who had B-cell acute lymphoblastic leukemia. Now blinatumomab has already been added as a standard of care to adults who have ALL. This was the first study to show an improvement in disease-free survival in children when a monoclonal antibody was added to standard chemotherapy.
There was also another great abstract looking at a Car T-cell therapy for children with relapsed or refractory acute lymphoblastic leukemia, which showed remarkable response rates when we focus on diet and lifestyle.
There were some abstracts that were really interesting about the effect of diet on pretty complicated hematopoietic conditions. For example, there was one study that looked at fiber intake and showed that increased fiber intake resulted in lower rates of graft versus host disease in patients who were receiving hematopoietic cell transplantation .
And our group, in a study through the National Heart, Lung and Blood Institute, looked at the association between smoking and mutations in myelodysplastic syndromes and were able to demonstrate that smoking was related not only to the number of mutations, but very specific types of mutations. And interestingly, the exact same types of mutations in myelodysplastic syndromes that are seen in association with smoking in lung cancer.
Then there were some studies that looked at, as I mentioned, treating almost cancers. There was one in particular looking at daratumumab monotherapy versus active monitoring in patients with smoldering multiple myeloma. Now, this study was simultaneously published in New England Journal and showed a delay in progression to multiple myeloma in those patients who were treated with daratumumab versus those who weren't. We anticipate that this will be a somewhat controversial finding.
There's more and more of a movement to treating conditions earlier in their diagnosis before they become more severe cancers. Now, it may be possible that in doing that, patients are able to have better outcomes. The risk of that, of course, is that patients who are treated earlier may unnecessarily be treated earlier before their disease becomes more severe. We may be exposing patients to chemotherapy prematurely.
Moving forward. I think what we're seeing more and more is a focus on measurable residual disease. So classically, we treat people for cancer. We hopefully get those folks into remission. And remission is defined for patients who have diagnoses like leukemia as looking in the bone marrow and not finding any leftover leukemia or for patients who have lymphoma, it's resolution of swollen lymph nodes. Well, it turns out that these folks who have what we refer to as a morphologic or radiographic remission may have some leftover cancer that we're just not seeing. And we're now able to detect that leftover cancer at 1 in 1,000 cells, 1 in 10,000, even 1 in 100,000 cells that are left over. And as we're able to detect this measurable residual disease, we're increasingly, reflexively, treating it and seeing if those folks can obtain an even deeper remission and therefore a prolonged overall survival.
5-Year Follow-up Analysis from ZUMA-5: A Phase 2 Trial of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma
My name is Dr. Sattva Neelapu and I am Professor and Deputy Chair in the Department of Lymphoma and Myeloma at MD Anderson Cancer Center in Houston, Texas. My interest is to treat patients with lymphoma and develop novel immune therapies, including Car T-Cell therapy in patients with B-cell lymphoma and T-cell lymphoma.
Axi-cel is an autologous entity anti CD 19 Car-T cell therapy that's previously been approved for treatment of patients with diffuse large B-cell lymphoma and follicular lymphoma.
What we presented at the ASH 2024 meeting is a five-year update on a Phase 2 study of Axi-cel in patients with relapsed or refractory indolent non-Hodgkin lymphoma called the Zuma-5 study.
This is a single arm, multicenter Phase 2 trial and to be eligible these patients had to have either relapsed or refractory follicular lymphoma grade 1 to 3A or relapsed refractory nodal or extra nodal marginal zone lymphoma. They have to have received at least two prior lines of therapy, including an anti-CD20 antibody and an Alkylating agent. And the primary end point for this study is overall response rate.
Following enrollment and leukapheresis of the patients, once the product has been generated, they receive conditioning chemotherapy with cyclophosphamide and fludarabine for over a period of three days. And after two days of rest ,they receive a single infusion of Axi-cel at a dose of 2 million CAR positive cells per kilogram of body weight.
We now have a median follow up of 66 months in the follicular lymphoma cohort and there were a total of 124 follicular lymphoma patients treated on the trial. And the median follow up on the marginal zone lymphoma patients was 56 months.
So, the best overall response rate was 90% and the best complete response rate was 75%. In the follicular lymphoma cohort, the complete response rate was much higher at 79%. And for marginal zone, it was 65%.
At data cut-off, 55% of patients are still in remission without needing any additional therapy. The median PFS is 62 months, and in the lymphoma specific survival analysis, we observed a plateau in the PFS co emerging after the two -ear time point with only four relapses after month 24 and only two relapses after one month 30.
So overall, these results indicate to us that Axi cel is a highly effective therapeutic option for these patients with very durable responses, even after five years of follow up and also in using long term survival in these patients. Over half the patients remain alive without the need for additional therapy.
What our data indicates with five-year follow up analysis is that Axi cel is potentially curative for at least a subgroup of patients with follicular lymphoma.
