Allogeneic Beats Autologous HSCT in Follicular Lymphoma, but Is It Worth It?

Zosia Chustecka

December 08, 2019

ORLANDO — A comparison of two types of transplant used in patients with relapsed follicular lymphoma has shown, for the first time, better overall survival following an allogeneic transplant (using stem cells from a donor) than with an autologous transplant (using stem cells harvested from the patient).

The researchers conclude that these long-term data (out to 200 months, about 16 years). should now be used in a collaborative effort to allow Medicare/Medicaid patients to receive allogeneic transplants for relapsed follicular lymphoma.  

However, an expert commenting on the findings said that the data do not actually show a cure with transplant, which is the aim of this intervention, and now that there are new therapies available, the expert also questioned whether going through a transplant is worth it.

The new data were presented here at the American Society of Hematology (ASH) 2019 annual meeting by Issa Khouri, MD, from the department of stem cell transplantation and cellular therapy at the University of Texas MD Anderson Cancer Center in  Houston.

Originally, the comparison was to be made in the prospective Blood and Marrow Transplant Clinical Trials Network randomized trial, but this study was closed early because of low accrual, Khouri explained. Thus, Khouri presented data from his own institution.

The study included 98 nonmyeloablative allogeneic transplant patients and 96 autologous transplant patients treated between 2000 and 2017.

The time from diagnosis to transplant was 38 months (3 years, 2 months) in both groups.

However, Khouri noted that there were significant differences between the two groups. For instance, more patients receiving allogeneic transplants had refractory disease compared with the autologous group (P = .018). In addition, a higher percentage of the allogeneic patients had bulky disease (P = .016), had a transplant >1st relapse (P = .001), received three or more prior chemotherapies (P = .003), and had a transplant between 2000 and 2005 rather than in later years (P = .033) compared with the autologous group.

The median follow-up for allogeneic transplant patients was 98 months (range, 3 months – 17.3 years) and for autologous transplants was 94 months (range, 1 month – 17.2 years).

All of the outcome measures were significantly better for the allogeneic transplant patients compared with the autologous transplant patients: overall survival was 62% vs 46% (P = .048), progression-free-survival was 52% vs 31% (P < .001), and the cumulative incidence of relapse was 15% vs 48% (P < .0001).

The significant differences remained in a propensity score matched analysis, Khouri commented.

"This is the first study to show that nonmyeloablative allogeneic transplantation confers a superior survival in patients with relapsed follicular lymphoma compared with autologous transplantation," Khoura concluded.

However, in commenting on this study, David Henry, MD, clinical professor of medicine at the University of Pennsylvania in Philadelphia, focused on the Kaplan-Meier curves of overall survival and progression-free survival in the abstract, and said there is no plateau showing for either curve. "This suggests that there is no cure with allogeneic transplants in follicular lymphoma," he commented in an MDEdge podcast previewing the meeting.

With all the new drugs that are now available, "I would have a hard time recommending allogeneic transplant for follicular lymphoma, especially before other things have been tried," Henry said. He mentioned the novel bispecific antibody mosunetuzumab (Genentech/Roche), which worked even in lymphoma patients who had not responded to CAR T cell therapy, as reported at this meeting.    

"I think this study does point to a problem with using allogeneic transplants in follicular lymphoma if the goal is a cure, because I see none based on this abstract," he said.

"I think that’s a little harsh," said Aaron Gerds, MD, from the Cleveland Clinic in Ohio, who was approached for comment. There is some relapse seen over the years after transplant, but the curves do start to plateau out at about 50 months, he told Medscape Medical News.

He also provided some context for these findings. This study began in 2000, when patients with relapsed follicular lymphoma had few options. There was only fludarabine with rituximab, or bendamustine with rituximab; after the patient relapsed, transplant was one of the only options that remained.

Since that time, there have been a number of novel drugs that have arrived on the scene, including ibrutinib (Imbruvica, Pharmacyclics/Janssen), the CAR T cells, the new bispecific antibody products, etc.

"The treatment landscape has changed dramatically," Gerds said, and it may be that some patients would do better or just as well on these new therapies than after a transplant.

However, there are economic considerations, he said. A transplant is a one-off treatment that probably costs in the region of $250,000. The two CAR T cell therapies that are currently on the market cost $373,000 and $475,000, respectively, and that is just the cost of the drug, to which hospitalization costs need to be added. Novel targeted therapies such as ibrutinib are expensive, and probably have to be taken indefinitely.  

So a transplant may be more cost effective, and the techniques are constantly being improved, Gerds added.

Khouri has disclosed no relevant financial relationships, but several coauthors have relationships with pharmaceutical industry, as listed in the abstract.

American Society of Hematology (ASH) 2019 Annual Meeting: Abstract 322. Presented December 7, 2019.

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