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Autologous Transplantation for Relapsed DLBCL in the CAR-T Therapy Era

 

Mehdi Hamadani, MD, Medical College of Wisconsin, Milwaukee, discusses an analysis evaluating the role of an autologous transplant in relapsed diffuse large B-cell lymphoma (DLBCL), which has declined by about 40-45% with the utilization of newer therapies, specifically CAR T-cell therapies. These results were presented at the virtual 2020 ASCO Annual Meeting.

Transcript

My name is Mehdi Hamadani. I'm a lymphoma physician at the Medical College of Wisconsin in Milwaukee.

Recently, at the 2020 American Society of Clinical Oncology meeting, we presented the CIBMTR registry data looking at the role of an autologous transplant in patients with diffuse large B‑cell lymphoma who have achieved only a PET‑avid or PET‑positive partial remission going into the transplant procedure.

Our retrospective registry‑based analysis was prompted by recent data from our group at CIBMTR, that has shown that in the last 2 to 3 years, the number of autologous transplant procedures, which is a curative therapy for patients with diffuse large B‑cell lymphoma, in the US have declined by about 40 to 45%.

Our hypothesis was that this change in the utilization of autologous transplant in these patients is largely driven by routing some of diffuse large B‑cell lymphoma patients to newer therapies, specifically CAR T‑cell therapy, in lieu of an autologous transplant procedure.

In talking to our colleagues across the country, we were aware of practice in many centers, specifically in lymphoma patients who after relapsing...If a group of diffuse large B‑cell lymphoma patients are not able to achieve a complete PET‑negative remission, such patients, in some institutions, are offered a CAR T‑cell‑based therapy instead of an autologous transplant.

That sort of shift in practice prompted this analysis. In our group, since the original randomized studies that looked at the role of autologous transplant in aggressive lymphomas, specifically diffuse large B‑cell lymphoma, required achieving at least a partial remission as eligibility for this procedure.

In the modern era, we wanted to ask this question specifically in this histology to see if autologous transplant can rescue patients who are responding to chemotherapy but who have not achieved a complete remission.

Our data included about 250 diffuse large B‑cell lymphoma patients who were transplanted in the US in the last 10 years or so. These patients were patients who were responding to whatever salvage regimen they were getting, but they had PET‑positive residual disease going into the transplant procedure.

Our data shows that in these patients, the long‑term cure rates for transplant at 3 years were about 50% and at 5 years were about 40%, arguing that autologous transplant in this setting can cure a reasonable subset of patients.

This data, while retrospective, procured from a registry setting are very important for at least two or three reasons, number one being 40% cure rate with the very low non‑relapse mortality or transplant‑related mortality rates associated with autologous transplant in the current era are very important.

The second point is that in these chemo‑sensitive patients, we have no data that are published, to my knowledge at least, that show that CAR T‑cell therapies is more curative in this setting rather than an autologous transplant. There are obviously cost considerations. CAR T‑cell therapy procedures are way more expensive than an autologous transplant procedure.

The last point being if autologous transplant cures about 40% of the patients, the remaining 60% of the patients after failing an autologous transplant can still be cured with a CAR T‑cell procedure, but you can't do an autologous transplant after a CAR T‑cell procedure fails.

If you do some rough math in your head, CAR T‑cell cures about 40% of patients who actually get CAR T‑cell with refractory disease. We don't know what CAR T‑cell performance in patients with partial remission is, but let's say CAR T‑cells would cure maybe 50% of those patients.

If you do rough math, if patients in partial remission only get CAR T‑cells as a get‑go, out of 100 patients, we'll be curing about 50 patients. If you apply the same logic to these patients getting autologous transplants, if you start with 100 patients, autologous transplant will cure about 40 of those patients.

The remaining 60 patients can subsequently go under CAR T‑cell procedure. Let's say CAR T‑cell cures 40 to 50% of those additional patients. Then we are really looking at about 60 to 70% of patients total cured using CAR T‑cell and autologous transplant in a sequential manner.

Because of all these highlighted reasons, in my opinion, in chemo‑sensitive patients, autologous transplant outside the setting of a clinical trial, as of today, is still the standard of care.

There are obviously at least 3 randomized trials ongoing in a subset of diffuse large B‑cell lymphoma with early failures that are comparing the approach of giving chemotherapy to establish chemosensitivity, followed by autologous transplant in sensitive patients versus going forward with a CAR T‑cell procedure from the get‑go.

It is plausible that those trials, when the data are available, may change our practice, but our practice needs to be guided by data.

Right now, data are not available to justify routine use of CAR T‑cell procedures in relapsed diffuse large B‑cell lymphoma patients who have shown evidence of chemosensitivity. In these patients, the standard of care still remains high‑dose therapy and autologous transplant.

Thank you for your attention.

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