Novel Regimen Shows Promise for Multiple Myeloma, Myelofibrosis


Researchers used split-dose busulfan, fludarabine, and post-transplant cyclophosphamide on 6 patients in a phase 2 study, and further research is warranted.

3D rendering of abnormal plasma cell in multiple myeloma: ©LASZLO -

3D rendering of abnormal plasma cell in multiple myeloma: ©LASZLO -

A small phase 2 study showed relatively safe and favorable outcomes using a novel myeloablative regimen of split-dose busulfan, fludarabine, and post-transplant cyclophosphamide for patients with myelofibrosis (MF) and multiple myeloma (MM).1 

At 1 year, the non-relapse mortality (NRM) ratewas 33.3%, and the overall survival (OS) rate was 50% among the 6 patients included in the study. Incidences of acute and chronic graft-versus-host disease (GVHD) were 33.3% and 16.7%, respectively.

Further, durable remissions were observed in patients surviving beyond 1 year (MF=1, MM=2) with a median follow-up of 42 months.

“The treatment landscape for MM has changed dramatically in the last 3 years, particularly for those with higher-risk disease…Although the 2MM patients on this trial maintained durable remissions at 1-year post-transplant, a larger study population would be needed to validate this finding, as well as explore the role of novel maintenance strategies, like pomalidomide, following alloHSCT,” according to the authors of the study in findings published in Leukemia Research Reports.

The study enrolled a total of 6 patients, including 4 with MF and 2 with MM. All patients were White, the median age was 55, and the oldest patient was 69 years old. Five of the 6 (83.3%) patients were female. Four out of 6 patients had a matched sibling donor, 1 had a matched unrelated donor, and 1 had an unrelated donor.

The primary end point was NRM on day +100. Secondary end points were NRM at day +365, incidence of acute and chronic GVHD at day +365, OS, disease-free survival (DFS) at day +365, and clinical and molecular response at day +365.

The final regimen patients received was 3.2 mg/kg/dose of busulfan (area under the curve target of 76.8-86.4 mg x h/L) and 30 mg/m2/day of fludarabine administered on days -5 through -2 before stem cell infusion. Patients received 50 mg/kg of cyclophosphamide as GVHD prophylaxis of days +3 and +4 along with tacrolimus and mycophenolate mofetil beginning on day +5.

The NRM rate on day +100 was 16.7% (1 of 6 patients). The patient failed to engraft and died of sepsis on day +30. The NRM rate on day +365 was 33.3% (2 of 6 patients). The second death was due to severe pneumonia. A third patient died after disease relapse and progression. All 3 patients alive at day +365 were free from disease. The 1-year OS was 50%. Additionally, the regimen led to notable serious adverse events (SAEs).

One of 3 patients had chronic GVHD, displaying as a mild skin rash. No patients experienced disease relapse. Patients with MM were administered pomalidomide (Pomalyst) maintenance therapy of 1-2 mg daily every 21 days starting after day +100.

“Although the rate of SAEs was high, the vast majority occurred in the single patient who failed to engraft and died on day +30. The remaining 3 patients who had SAEs experienced either a single SAE, or 2 events of the same SAE. Despite this, the numbers seen here are higher than those found by prior studies with more conventional myeloablative preparative regimens, attributable to our small study population,” study authors wrote.1

A phase 1/2 study (NCT03795597) at Loyola University is evaluating busulfan and melphalan with carfilzomib (Kyprolis) as a preparative regimen for patients with MM. An estimated 36 patients are enrolled, and the estimated completion date is November 2023.2

1. Trunk AD, Patel SS, Prchal JT, Sborov DW, Zander AR, Lee CJ. Allogeneic stem cell transplant for multiple myeloma & myelofibrosis with split-dose busulfan, fludarabine & cyclophosphamide. Leuk Res Rep. 2023;20:100388. Published 2023 Aug 26. doi:10.1016/j.lrr.2023.100388
2. Busulfan, melphalan, escalating carfilzomib conditioning auto stem cell transplantation for multiple myeloma (MM) (BuMelCarAuto). Updated April 26, 2021. Accessed October 6, 2023. 
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