Pemigatinib Represents Transformative Treatment for Myeloid/Lymphoid Neoplasms With FGFR1 Rearrangement

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Partner | Cancer Centers | <b>The University of Texas MD Anderson Cancer Center</b>

Srdan Verstovsek, MD, PhD, discusses the clinical implications of the FDA approval of pemigatinib, the results of the FIGHT-203 trial, and the need to conduct chromosomal analysis for patients with myeloid/lymphoid neoplasms.

The efficacy displayed by pemigatinib (Pemazyre) in the treatment of patients with myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement has emphasized the need for chromosomal analysis to identify translocation of chromosome 8p11, according to Srdan Verstovsek, MD, PhD.

On August 26, 2022, the FDA approved pemigatinib for the treatment of adults with relapsed or refractory MLNs and FGFR1 rearrangement, based on data from the phase 2 FIGHT-203 trial (NCT03011372). Patients with chronic phase in the marrow with or without extramedullary disease (n = 18) achieved a complete response (CR) rate of 78% (95% CI, 52%-94%) with a median time to CR of 104 days (range, 44-435). The median duration of CR was not yet reached (range, 1+ to 988+ days).

“So far, I have received such positive feedback from my colleagues in the field who have used [pemigatinib]. It is priority for all of us in hematology to think about these rare patients who can be identified based on analysis of chromosomes,” Verstovsek said. “[Chromosome] 8p11 is the abnormality that we look for, and if we forget or overlook those findings, we are missing an extraordinarily effective therapy for these patients.”

In an interview with OncLive®, Verstovsek discussed the clinical implications of the FDA approval of pemigatinib, the results of the FIGHT-203 trial, and the need to conduct chromosomal analysis for patients with MLNs. Verstovsek is the United Energy Resources, Inc. Professor of Medicine and a hematologist/oncologist at The University of Texas MD Anderson Cancer Center.

OncLive®: What is the significance of the FDA approval of pemigatinib for patients with MLNs with FGFR1 rearrangement?

Verstovsek: We first need to recognize that MLNs with eosinophilia and a rearrangement of the FGFR1 gene are rare. We don’t have knowledge of [exactly] how many patients exist with that condition, but hopefully that will change as we identify them.

Because of the development of pemigatinib, which is an FGFR1 inhibitor, these patients [now] have a transformative therapy. In the past, the outcomes [for] these patients were very bad. There were no effective therapies, and chemotherapy and supportive care did not provide meaningful benefit. The average survival [ranged from 12 to 18 months].

Now we have an inhibitor of a driver of this disease and a medication that can eliminate this disease in [a substantial number] of patients. This is an unheard of and transformative event. I hope that through education, we are going to identify many more of these patients to help them live a normal life for as long as possible.

Please expand on the mechanism of action of pemigatinib.

In patients with MLNs with eosinophilia and this particular abnormality in the FGFR1 gene, abnormalities in chromosomes lead to activation of the gene. This is very important [to know] for everyday practice. [The abnormalities stem from] translocation involving chromosome 8p11. These translocations that happen, including the breakage of the chromosome and translocations between them that involve 8p11, would activate FGFR1. The gene makes a lot of protein, FGFR is very high, and that is the driver behind the disease.

There may be some other reasons for the disease’s aggressiveness. That’s important to know because many patients present with more of a chronic myeloproliferative neoplasm, but some patients present with acute leukemia, myeloid or lymphoid [disease], or even lymphoma. There might be some other factors that contribute to the disease behavior. However, we now have proof that FGFR1 is the driver of the disease. Inhibiting FGFR1 [can eliminate many of the] symptoms and signs of the disease.

If we want to have a message for every practice, [you must] look for a patient’s chromosomal analysis results, [also known as] cytogenetics or a karyotype test, and identify patients that have translocations that involve chromosome 8p11. These are the patients that are highly likely to have an FGFR1 rearrangement, and they are candidates to receive pemigatinib.

Please discuss the pivotal efficacy data from the FIGHT-203 trial that led to the approval of pemigatinib. Was there anything particularly surprising about these findings?

We had high hopes that pemigatinib, as an inhibitor of FGFR1, would provide extraordinary clinical benefit. However, the reality was that because of a diversity of the clinical presentations from the chronic myeloproliferative neoplasms [MPNs] to lymphoma, acute lymphocytic leukemia, and acute myeloid leukemia [AML], there were questions. I’m happy to say that the extraordinary benefits that were seen across the board are amazing.

We had [a CR rate of 78%], and the duration of the benefit has not yet been reached in the study. The study has been ongoing [for approximately] 5 years now. You can imagine what transformative effect this would have on a patient who would usually live for [12 to 18 months]. Even in the setting of AML, patients can eliminate their disease just by taking 1 pill per day. It’s extraordinary for even the sickest patients.

In the future, I would envision that we will be combining pemigatinib with other active agents for those advanced cases to make it even better. Judging by elimination of the chromosomal abnormality of 8p11, we really have something on our hands that nobody really expected.

Given that the safety profile is mostly consistent with the known toxicities from FGFR inhibition, are there any notable adverse effects (AEs) to mention? Are there any patients for whom you would not recommend pemigatinib?

The AEs of an FGFR inhibitor have been known because they are also approved for other solid tumor types. That toxicity profile is seen in patients with hematological diseases as well, but AEs will not [prevent] any [individual] from [receiving] pemigatinib in hematological malignancies, including those with MLNs and FGFR1 rearrangement.

The benefit is extraordinary and outweighs any risk. Therefore, I would advise looking for these patients and treating them properly. Of course, dose modifications are [possible]. There is a preferred starting dose, and that can be modified, if necessary. This is how the management of the patients happens in real life, because the first [goal] is to eliminate the disease, then maintain patients on active therapy, not allowing the disease to come back. The patient’s quality of life is then priority, and dose adjustments [to help a patient] have a good quality of life for as long as possible is the ultimate goal.

What ongoing research is being conducted at MD Anderson Cancer Center?

Here at MD Anderson Cancer Center, we have developed the largest single institution for MPNs in the world. There are numerous studies for other types of MPNs, including patients with essential thrombocythemia, polycythemia vera, and myelofibrosis. We are in the midst of performing a number of phase 3 randomized studies for a possible approval of new medications for these conditions as well. Please join us and send patients to join these efforts.


FDA approves pemigatinib for relapsed or refractory myeloid/lymphoid neoplasms with FGFR1 rearrangement. FDA. August 26, 2022. Accessed September 8, 2022.