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IACH 2021 | Transplantation for NHL and B-ALL in the era of CAR-T

Bhagirathbhai Dholaria, MBBS, of Vanderbilt University Medical Center, Nashville, TN, discusses the role of transplant for the treatment of B-cell non-Hodgkin lymphoma (B-NHL), and B-cell acute lymphoblastic leukemia (B-ALL) in the era of chimeric antigen receptor (CAR) T-cell therapy. Hematopoietic stem cell transplantation (HSCT) has been the standard treatment for eligible patients with these diseases; however, recently, CAR T-cell therapies are fulfilling an increasingly prominent role in the field. Dr Dholaria explains that patients with B-ALL tend to relapse even after initial complete remission and thus they are usually offered allogenic stem cell transplant after CAR T-cell therapy. Dr Dholaria argues that in the future, improved monitoring dynamics will help identify patients in need of an allotransplant. On the contrary, data has shown that most patients with NHL who achieve complete remission will not relapse and therefore allogenic stem cell transplants are generally not offered to these patients. This interview took place at the 4th Annual Meeting of the International Academy for Clinical Hematology (IACH), which took place virtually in 2021.

Transcript (edited for clarity)

As we all know, CAR-T therapy has been increasingly used for many hematological malignancies and mainly non-Hodgkin lymphoma and B-cell acute lymphoblastic lymphoma. We have now multiple FDA approved CAR T-cell products available in the market. And these drugs are extremely effective in getting patients with even very refractory disease into getting into complete remissions.

However, we and others have described that outcomes of patients who achieve a complete remission after an allogenic transplant, especially acute lymphoblastic lymphoma patients, they tend to keep relapsing, especially the adult patients...

As we all know, CAR-T therapy has been increasingly used for many hematological malignancies and mainly non-Hodgkin lymphoma and B-cell acute lymphoblastic lymphoma. We have now multiple FDA approved CAR T-cell products available in the market. And these drugs are extremely effective in getting patients with even very refractory disease into getting into complete remissions.

However, we and others have described that outcomes of patients who achieve a complete remission after an allogenic transplant, especially acute lymphoblastic lymphoma patients, they tend to keep relapsing, especially the adult patients. In pediatric wards, we know that these patients can achieve remission and hopefully cure, but at least in adult ward, we have keep seeing patient increasingly relapsing even after they initially achieved complete deep remission with the CAR-T.

With the stem cell transplantations, the role keeps evolving. Generally, any patients who relapse after initial induction therapy with ALL should be offered an allogeneic stem cell transplantation. But however, now with increasingly effective salvage therapies, we are kind of oppose this question that everybody still need the stem cell transplantation after CAR-T. And the answer is it’s kind of varies from patient to patient. In our practice, we’ve been offering it to anybody with relapse/refractory disease after CAR-T, at least in all the adult patients. But I think in the future, once we get better at monitoring the in vivo CAR-T dynamics and also strict monitoring of MRD pre- and post- CAR-T, this will better able to assist, kind of decide which patients will need allogeneic transplant consultation after CAR-T for B-cell ALL.

In non-Hodgkin lymphoma, the jury is still out. We know that around 30 to 40% of those patients are in long-term remissions. Now, we have data over five years follow-up from the ZUMA study and the patients who achieved early complete remission at day 90, majority of them are not relapsing. So generally, we have not been offering conservative allo-transplant for non-Hodgkin lymphoma patients once they achieve a complete remission after a CAR T-cell therapy. However, as we use CAR-T in other malignant hematological conditions, I think the role of allogeneic transplant will continue to evolve, especially as we get a better and effective CAR-T therapies for myeloid malignancy. I think most of us will still prefer consolidation with allogeneic transplant once this patient achieves complete remission. However, this field is moving rapidly in different directions. Different CAR-T products are being evaluated in different disease, at different stages, even. So, I expect this continue to evolve.

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Disclosures

Bhagirathbhai Dholaria, MBBS, has received research or grant support from Janssen, Takeda, MEI, Poseida, Angiocrine and Pfizer; and has received consultation/advisory board/employment fees from Jazz Pharmaceuticals.

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