Disease- and Patient-Related Factors Guide Decisions For Patients With Myelofibrosis Receiving allo-HCT

When considering patients with myelofibrosis for allogeneic hematopoietic stem cell transplant (alloHCT), it is crucial to take both disease-related factors and patient-related factors into consideration, said Roni Tamari, MD, bone marrow transplant specialist, Memorial Sloan Kettering Cancer Center (MSKCC), during a presentation at the Society of Hematologic Oncology (SOHO) 2024 Annual Meeting, held in Houston, Texas.

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Currently, alloHCT is the only curative treatment for patients with myelofibrosis, and according to US reports from 2001 to 2018, transplant outcomes for this patient population improving. Tamari noted that outcomes improved, with overall survival (OS) increasing from approximately 50% in 2001 to 2005, to approximately 60% in 2011 to 2018. Additionally, she acknowledged that these improved outcomes might be a result of patients receiving Janus kinase (JAK) inhibitors prior to transplant to improve their performance status.

Further, 3-year OS was better for patients with myelofibrosis who received a transplant from a matched related donor (69.1% [95% CI: 64.7%-73.8%]) compared with those with a matched unrelated donor (58.9% [95% CI: 55.7%-62.4%]). The trend was similar for patients with other myeloproliferative neoplasms (MPNs), with those being matched to a related donor having a slightly better 3-year OS (55.9% [95% CI: 49.9%-62.5%]) than those with a matched unrelated donor (57.0% [53.0%-61.4%]).

Tamari explained that when considering patients for alloHCT, the most significant factors to take into consideration are disease-related and patient-related. Disease-related factors revolve around several prognostic systems (eg, Dynamic International Prognostic Scoring System [DIPSS], Mutation and Karyotype-Enhanced International Prognostic Scoring System, and Myelofibrosis Transplant Scoring System), whereas patient-related factors involve age and comorbidities, and specifically for myelofibrosis, spleen size, anemia, and iron overload must be addressed.

“So, to answer the question of who we should transplant, we base a lot on this analysis and saying that patients with more advanced disease, DIPSS, intermediate 2 and high-risk disease…these are the patients that we should probably transplant. And with the patients [who have] low-risk disease, [we should] not offer transplant early on,” explained Tamari.

In addition to blood counts and patient age, the donor was an important factor in transplant outcomes similar to what was previously discussed, noted Tamari. Patients over the age of 50 who underwent transplant from an HLA-match unrelated donor was associated with a higher hazard risk of mortality, compared with those who underwent transplant with an HLA-match related donor. This mortality risk was even higher when patients with advanced anemia underwent transplant with a mismatched unrelated donor.

As for patient-related outcomes, Tamari explained that there is no consensus of spleen measurement or size that can predict transplant outcomes; however, there are data that show an enlarged spleen is associated with an increased relapse in addition to delayed engraftment. Different interventions—such as reducing spleen size pre-alloHCT through JAK inhibitors pre-transplant, splenic radiation, or splenectomy—may be performed, but Tamari acknowledged that these interventions have yet to be compared.

“[Additionally,] severe anemia—as we saw in the different prognostic system—has a very important effect in terms of how advanced [myelofibrosis] is, but when we think about transplant, it has another effect in that patients who come to transplant after many transfusions can develop autoimmunization and iron overload. Both have been associated with worse transplant-related mortality,” explained Tamari. “So, these are things that really we need to look at before we take patients to transplant or when we plan the transplant.”

Further, in a retrospective analysis that enrolled 69 patients with myelofibrosis who underwent alloHCT with a haploidentical donor (mismatched unrelated) while receiving post-transplantation cyclophosphamide-based platform for graft-versus-host disease prophylaxis, better outcomes were reported. Three-year OS was approximately 72%, but progression-free survival was lower at 44%. Tamari explained that this is particularly interesting, because in other diseases—such as acute leukemias and myelodysplastic syndromes—outcomes that use alternative donors are similar to those that use HLA-match donors.

In addition, Tamari noted that there is no conditioning method, whether it is reduced-intensity conditioning or myeloablative conditioning that has demonstrated stronger outcomes or inferiority. She suggested that decisions can be made on conditioning depending on the patient’s age and their tolerability. For example, for older patients with substantial comorbidities may be more suitable for reduced-intensity conditioning, whereas myeloablative conditioning would be a better fit for a younger patient.

Tamari concluded the presentation by emphasizing the challenges that remain for alloHCT in the myelofibrosis space. She explained that, although the number of patients with myelofibrosis who receive alloHCT is increasing, it is still considered a rare indication. For example, at MSKCC—which is considered to be a large transplant center—only 10 to 12 patients with myelofibrosis per year undergo alloHCT. Tamari explained that because this is a rare indication, it is difficult to recruit patients with prospective clinical studies. These analyses typically include patients over many years.

“[One last thing] that is very critical [is] the definition of relapse post-transplant. [Myelofibrosis] is a disease that, morphologically, we see the same changes remaining in the bone marrow even after transplant. So, the question is, when we do a bone marrow to assess disease status post-transplant and we still see fibrosis, what is the significance of that?” concluded Tamari. “Also, patients remain transfusion-dependent at times after transplant, so it's really, really important for us in the [myelofibrosis space] to try to come up with a definition of what relapse means…I think this is something that we're really struggling a lot with.”

REFERENCE

Tamari, R. Session V—MyeloproliferatIVe Neoplasms: Who, When, and How to Transplant Patients With Myelofibrosis. Society of Hematologic Oncology Annual Meeting; Houston, Texas. September 4, to September 7, 2024.