Pemigatinib Shows Promising Efficacy as Myeloid/Lymphoid Neoplasms Treatment

In data from a phase 2 clinical trial presented at the 60th ASH Annual Meeting & Exposition in San Diego, California, investigational therapy pemigatinib appeared to be effective and generally well-tolerated in patients with a specific type of myeloid/lymphoid neoplasm (MLN).

For the open-label, multicenter trial, investigators from the University of Texas M.D. Anderson Cancer Center in Houston recruited 14 participants in order to test the efficacy and tolerability of pemigatinib in FGFR1-rearranged MLN patients. The patients were all over 18 years of age and progressed on more than 1 prior treatment. The analysis included 10 patients who had ≥ 1 response assessment.

Pemigatinib is a selective, potent, oral inhibitor of FGFR1, 2, and 3, and in prior studies has been effective in patients with FGFR1-active tumors, such as cholangiocarcinoma and urothelial carcinoma.

The team noted that these patients have a rearrangement of FGFR1 on chromosome band 8p11, which is rare and characterized by heterogenous presentation of myeloid and/or lymphoid proliferation. They also noted that patients often experience extramedullary involvement and rapid progression to blast phase.

The patients in this study received a daily oral dose of pemigatinib 13.5 mg for 2 weeks, followed by 1 week off. This 21-day cycle continued until disease progression or an unacceptable level of toxicity was reached. The patients then received an average of 6.9 cycles of pemigatinib, ranging from 2-12 cycles.

Eight patients had a major cytogenic response, including 6 patients with complete cytogenic response and 2 with partial cytogenic response. Eight patients also had a complete clinical response or partial clinical response in bone marrow, peripheral blood, and extramedullary disease. One patient involved in the study died of progression to myeloid blast crisis. Seven patients remain in ongoing pemigatinib treatment.

Though there were no drug-related adverse events that led to dose interruption, reduction, or discontinuation, the most common adverse events related to treatment were hyperphosphatemia (in 7 patients), diarrhea (5 patients), and anemia (5 patients). Other adverse events included alopecia, dyspepsia, and fatigue.

“This therapy, if approved, would be essential for patients with this specific type of MPN, as there is no active therapy at all, and this targeted agent results in high rate of complete clinical response and partial clinical response,” study author Srdan Verstovsek, MD, PhD, told Rare Disease Report.

The team noted that current treatment options, such as chemotherapy, are largely ineffective. To date, no targeted treatment has been discovered, and stem cell transplant stands as the only “potentially curative option.”

The patients involved in this study were ineligible for stem cell transplant, though 2 were bridged to that option.

“Pemigatinib showed promising efficacy, with an 80% major cytogenic response rate accompanied by complete or partial remission and was generally well tolerated by patients with FGFR1—rearranged MLN,” the study authors concluded. “The protocol was amended to allow continuous dosing, and the study is currently enrolling.”

The abstract, titled “Interim Results from Fight-203, a Phase 2, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Pemigatinib (INCB054828) in Patients with Myeloid/Lymphoid Neoplasms with Rearrangement of Fibroblast Growth Factor Receptor 1 (FGFR1),” was presented at the at the 60th ASH Annual Meeting & Exposition.