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CHIPs and BEAMing SMILEs: A Bone Marrow Transplant Update

December 13, 2022

For the malignant hematologists and bone marrow transplanters out there, the word “smile” has a very different connotation in the context of the ill-named chemotherapy regimen SMILE. Yet, in the purest sense of the word, the oral abstract sessions on bone marrow transplant, may put a genuine smile on our faces. The sessions on Monday, December 12, focused on a panoply of topics applicable to the care of patients undergoing allogeneic transplant and built upon autologous transplant presentations from Sunday, December 11. The autologous transplant discussion centered on the efficacy of replacing BCNU/carmustine with bendamustine in the conventional BEAM (BCNU, etoposide, ara-C, melphalan) regimen, addition of consolidative pembrolizumab following autologous transplantation in patients with T-cell lymphoma, and utilization of specific variants of clonal hematopoiesis of indeterminate potential (CHIP) to assess risk of therapy-related myeloid neoplasms in patients undergoing autologous transplantation.

With much fanfare and excitement in the air, the oral presentations from Monday, December 12, did not disappoint. Some of the highlights are included below.

The first set of presentations included therapeutic strategies to improve upon conditioning chemotherapy, which is a critical component of allogeneic hematopoietic stem cell transplantation. Important data were presented on the preliminary efficacy and safety of a novel nonmyeloablative regimen for severe aplastic anemia consisting of fludarabine, cyclophosphamide, and rituximab. Additionally, for patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplasia with excess blasts, a new CD117-Amanitin antibody drug conjugate showed efficacy and safety as a single-agent myeloid conditioning regimen in a phase I/II clinical study.

The next series of presentations focused on identifying strategies to mitigate both acute and chronic graft-versus-host disease (GVHD) without compromising the engraftment of donor cells. Therapies with preliminary safety and efficacy include addition of the novel JAK1 inhibitor, itacitinib, to traditional tacrolimus or sirolimus GVHD prophylaxis after fludarabine and melphalan conditioning, as well as addition of RGI-2001, a novel glycolipid that activates invariant natural killer cells, to tacrolimus and methotrexate for prevention of GVHD. Likewise, in the haploidentical transplant setting, the Orca-Q product, which contains enriched CD34+ stem cells combined with specific T-cell subsets, showed lower incidence of GVHD with tacrolimus and enabled the elimination of post-transplant cyclophosphamide or mycophenolate mofetil. For the treatment of acute GVHD, the JAK1/2 inhibitor baricitinib was found to be efficacious.

Additionally, new approaches to mitigate relapse after allogeneic transplant in patients with high-risk disease were introduced. Data on the use of the IDH-2 inhibitor enasidenib as maintenance therapy post-allogeneic transplant in AML patients with IDH2 mutation were presented. Similarly, for patients with AML harboring FLT3-ITD mutations, results from the phase III QuANTUM-first trial showed improved overall survival with the addition of the FLT3 inhibitor quizartinib to intensive induction, consolidation and post-allogeneic transplant conditioning monotherapy in patients undergoing allogeneic hemopoietic stem cell transplant in first complete remission. Other approaches include the addition of inotuzumab ozogamicin after allogeneic transplant in patients with acute lymphoblastic leukemia, as well as the addition of the histone deacetylase inhibitor romidepsin as maintenance in patients receiving an allogeneic stem cell transplant for relapsed and refractory T-cell malignancies.

Lastly, one of the most important considerations for those who undergo an allogeneic transplant is survivorship and quality of life. For many patients, receiving care at a specialized transplant center requires spending months away from  home. To that end, a study that assessed a shared model of care between a transplant physician and a local hematologist/oncologist, versus care delivered solely at a specialized center in the post-transplant setting, revealed comparable day 100 nonrelapse mortality. Similar models to improve quality of life for patients undergoing allogeneic transplant are of critical importance.

Overall, the bone marrow transplant sessions highlighted important advances that will surely impact patient care in the years to come. Maybe one day we will move beyond chemotherapy regimens like BEAM and SMILE so that we will not dip in the CHIPs of the past, and move toward a brighter, chemotherapy-free future.

Dr. Hermel indicated no relevant conflicts of interest.


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